FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Thase, ME Sloan, DM AF Thase, Michael E. Sloan, Diane M. BE Schatzberg, AF Nemeroff, CB TI Venlafaxine and Desvenlafaxine SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; EXTENDED-RELEASE VENLAFAXINE; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; PREMENSTRUAL DYSPHORIC DISORDER; TREATMENT-RESISTANT DEPRESSION; POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER C1 [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sloan, Diane M.] Advogent, Wayne, NJ USA. RP Thase, ME (reprint author), Univ Penn, Sch Med, Dept Psychiat, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 140 TC 2 Z9 2 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 439 EP 452 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700023 ER PT J AU Marder, SR Wirshing, DA AF Marder, Stephen R. Wirshing, Donna A. BE Schatzberg, AF Nemeroff, CB TI Clozapine SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID DRUG-INDUCED PSYCHOSIS; INDUCED WEIGHT-GAIN; CHILDHOOD-ONSET SCHIZOPHRENIA; SENSORIMOTOR GATING DEFICITS; SERUM TRIGLYCERIDE LEVELS; COLONY-STIMULATING FACTOR; SUBSTANCE USE DISORDER; INDUCED AGRANULOCYTOSIS; DOUBLE-BLIND; TREATMENT-RESISTANT C1 [Marder, Stephen R.] Univ Calif Los Angeles, Sect Psychosis, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Marder, Stephen R.] W Los Angeles Vet Affairs Med Ctr, Desert Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Wirshing, Donna A.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Marder, SR (reprint author), Univ Calif Los Angeles, Sect Psychosis, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. NR 149 TC 1 Z9 1 U1 4 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 555 EP 571 PG 17 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700029 ER PT J AU Ballon, JS Wirshing, DA Schulz, SC AF Ballon, Jacob S. Wirshing, Donna A. Schulz, S. Charles BE Schatzberg, AF Nemeroff, CB TI Olanzapine SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID PLACEBO-CONTROLLED-TRIAL; OBSESSIVE-COMPULSIVE DISORDER; INDUCED WEIGHT-GAIN; BORDERLINE PERSONALITY-DISORDER; ATYPICAL ANTIPSYCHOTIC-DRUGS; PROMINENT NEGATIVE SYMPTOMS; RANDOMIZED CONTROLLED-TRIAL; D-2 RECEPTOR OCCUPANCY; METHYL-D-ASPARTATE; ORALLY DISINTEGRATING OLANZAPINE C1 [Ballon, Jacob S.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Schulz, S. Charles] Univ Minnesota, Dept Psychiat, Sch Med, Riverside, CA USA. [Wirshing, Donna A.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Wirshing, Donna A.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Ballon, JS (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. NR 202 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 573 EP 598 PG 26 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700030 ER PT J AU Goff, DC AF Goff, Donald C. BE Schatzberg, AF Nemeroff, CB TI Risperidone and Paliperidone SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID TREATMENT-RESISTANT SCHIZOPHRENIA; ACTING INJECTABLE RISPERIDONE; DOUBLE-BLIND; ANTIPSYCHOTIC-DRUGS; RECEPTOR OCCUPANCY; 5-HT2 RECEPTOR; SCHIZOAFFECTIVE DISORDER; ATYPICAL ANTIPSYCHOTICS; PSYCHOTIC-PATIENTS; AUTISTIC DISORDER C1 [Goff, Donald C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA USA. RP Goff, DC (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. NR 96 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 627 EP 640 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700033 ER PT J AU Freeman, MP Wiegand, CB Gelenberg, AJ AF Freeman, Marlene P. Wiegand, Christopher B. Gelenberg, Alan J. BE Schatzberg, AF Nemeroff, CB TI Lithium SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID BIPOLAR AFFECTIVE-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; MANIC-DEPRESSIVE ILLNESS; SINUS NODE DYSFUNCTION; HOSPITALIZED AGGRESSIVE-CHILDREN; TREATMENT-REFRACTORY DEPRESSION; RESISTANT UNIPOLAR DEPRESSION; TRAUMATIC STRESS DISORDER; DOUBLE-BLIND; MAINTENANCE TREATMENT C1 [Freeman, Marlene P.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. [Freeman, Marlene P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gelenberg, Alan J.] Healthcare Technol Syst Inc, Madison, WI USA. [Gelenberg, Alan J.] Univ Wisconsin, Madison, WI USA. [Wiegand, Christopher B.] Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. NR 318 TC 1 Z9 1 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 697 EP 717 PG 21 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700036 ER PT J AU Del Signore, SJ Amante, DJ Kim, J Stack, EC Goodrich, S Cormier, K Smith, K Cudkowicz, ME Ferrante, RJ AF Del Signore, Steven J. Amante, Daniel J. Kim, Jinho Stack, Edward C. Goodrich, Sarah Cormier, Kerry Smith, Karen Cudkowicz, Merit E. Ferrante, Robert J. TI Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Amyotrophic lateral sclerosis; riluzole; histone deacetylase inhibition; sodium phenylbutyrate; therapy ID NF-KAPPA-B; HISTONE DEACETYLASE INHIBITORS; NEUROPROTECTIVE AGENT RILUZOLE; MOTOR-NEURON DEGENERATION; SUPEROXIDE-DISMUTASE GENE; MOUSE MODEL; HUNTINGTONS-DISEASE; PROLONGS SURVIVAL; CONTROLLED TRIAL; COENZYME Q(10) AB Recent evidence suggests that transcriptional dysregulation may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). The histone deacetylase inhibitor, sodium phenylbutyrate (NaPB), is neuroprotective and corrects aberrant gene transcription in ALS mice and has recently been shown to be safe and tolerable in ALS patients while improving hypoacetylation. Since many patients are already on riluzole, it is important to ensure that any proposed therapy does not result in negative synergy with riluzole. The combined treatment of riluzole and NaPB significantly extended survival and improved both the clinical and neuropathological phenotypes in G93A transgenic ALS mice beyond either agent alone. Combination therapy increased survival by 21.5%, compared to the separate administration of riluzole (7.5%) and NaPB (12.8%), while improving both body weight loss and grip strength. The data show that the combined treatment was synergistic. In addition, riluzole/NaPB treatment ameliorated gross lumbar and ventral horn atrophy, attenuated lumbar ventral horn neuronal cell death, and decreased reactive astrogliosis. Riluzole/NaPB administration increased acetylation at H4 and increased NF-B p50 translocation to the nucleus in G93A mice, consistent with a therapeutic effect. These data suggest that NaPB may not interfere with the pharmacologic action of riluzole in ALS patients. C1 [Del Signore, Steven J.; Amante, Daniel J.; Kim, Jinho; Stack, Edward C.; Goodrich, Sarah; Smith, Karen; Ferrante, Robert J.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Dept Lab Med & Pathol, Boston, MA 02118 USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Kim, Jinho; Stack, Edward C.; Cormier, Kerry; Smith, Karen; Ferrante, Robert J.] New England Vet Adm, Ctr Geriatr Res Educ & Clin, Bedford, England. [Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA USA. RP Ferrante, RJ (reprint author), Bedford VA Med Ctr, GRECC Unit 182B, 200 Springs Rd, Bedford, MA 01730 USA. EM rjferr@bu.edu RI Hartman, Jessica/N-3210-2016 FU Veterans Administration (RJF and MEC) FX This work was supported by a Merit Review Award from the Veterans Administration (RJF and MEC). NR 47 TC 38 Z9 40 U1 2 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 2 BP 85 EP 94 AR PII 794885986 DI 10.1080/17482960802226148 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 415JZ UT WOS:000263931400004 PM 18618304 ER PT J AU Cudkowicz, ME Andres, PL Macdonald, SA Bedlack, RS Choudry, R Brown, RH Zhang, H Schoenfeld, DA Shefner, J Matson, S Matson, WR Ferrante, RJ AF Cudkowicz, Merit E. Andres, Patricia L. Macdonald, Sally A. Bedlack, Richard S. Choudry, Rabia Brown, Robert H., Jr. Zhang, Hui Schoenfeld, David A. Shefner, Jeremy Matson, Samantha Matson, Wayne R. Ferrante, Robert J. CA NE Als Consortium Natl VA Als Res Consortium TI Phase 2 study of sodium phenylbutyrate in ALS SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Clinical trial; amyotrophic lateral sclerosis; HDAC inhibition ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MOUSE MODEL; DIFFERENTIAL EXPRESSION; HUNTINGTONS-DISEASE; CONTROLLED TRIAL; DOSE-ESCALATION; GENES; MICE; PHENYLACETATE; MINOCYCLINE AB The objective of the study was to establish the safety and pharmacodynamics of escalating dosages of sodium phenylbutyrate (NaPB) in participants with ALS. Transcription dysregulation may play a role in the pathogenesis of ALS. Sodium phenylbutyrate, a histone deacetylase inhibitor, improves transcription and post-transcriptional pathways, promoting cell survival in a mouse model of motor neuron disease. Forty research participants at eight sites enrolled in an open-label study. Study medication was increased from 9 to 21 g/day. The primary outcome measure was tolerability. Secondary outcome measures included adverse events, blood histone acetylation levels, and NaPB blood levels at each dosage. Twenty-six participants completed the 20-week treatment phase. NaPB was safe and tolerable. No study deaths or clinically relevant laboratory changes occurred with NaPB treatment. Histone acetylation was decreased by approximately 50% in blood buffy-coat specimens at screening and was significantly increased after NaPB administration. Blood levels of NaPB and the primary metabolite, phenylacetate, increased with dosage. While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels. C1 [Cudkowicz, Merit E.; Andres, Patricia L.; Choudry, Rabia] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [Macdonald, Sally A.; Matson, Samantha; Matson, Wayne R.; Ferrante, Robert J.] Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. [Bedlack, Richard S.] Durham VA Med Ctr, Durham, NC USA. [Brown, Robert H., Jr.] Massachusetts Gen Hosp, Day Lab, Charlestown, MA USA. [Zhang, Hui; Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Shefner, Jeremy] SUNY Syracuse, Syracuse, NY USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, 13th St,Bldg 149,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org FU Department of Veterans Affairs; Muscular Dystrophy Association FX The study was supported by grants from the Department of Veterans Affairs and the Muscular Dystrophy Association. We thank the National VA ALS Registry, the study participants and their families, and the Safety Monitoring Committee members, Carl Leventhal, Terry Heiman-Patterson, and Michael McDermott. NR 27 TC 56 Z9 59 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 2 BP 99 EP 106 AR PII 901445108 DI 10.1080/17482960802320487 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 415JZ UT WOS:000263931400006 PM 18688762 ER PT J AU Bedlack, RS Silani, V Cudkowicz, ME AF Bedlack, Richard S. Silani, Vincenzo Cudkowicz, Merit Ester TI IPLEX and the Telephone Game: The difficulty in separating myth from reality on the internet SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; GROWTH-FACTOR-I; ALS; PROGRESSION; TRIAL C1 [Bedlack, Richard S.] Duke Univ, Med Ctr, ALS Clin, Durham, NC 27710 USA. [Silani, Vincenzo] Univ Milan, Milan Med Sch, IRCCS Ist Auxologico Italiano, Dept Neurol, Milan, Italy. [Silani, Vincenzo] Univ Milan, Milan Med Sch, IRCCS Ist Auxologico Italiano, Neurosci Lab, Milan, Italy. [Cudkowicz, Merit Ester] Harvard Univ, Sch Med, Mass Gen Hosp, Boston, MA USA. RP Bedlack, RS (reprint author), Duke Univ, Med Ctr, ALS Clin, Box 3333, Durham, NC 27710 USA. EM Bedla001@mc.duke.edu OI Silani, Vincenzo/0000-0002-7698-3854 NR 12 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 3 BP 182 EP 184 AR PII 907234807 DI 10.1080/17482960802673059 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 447QC UT WOS:000266205200008 PM 19110985 ER PT J AU Qureshi, M Schoenfeld, DA Paliwal, Y Shui, A Cudkowicz, ME AF Qureshi, Muddasir Schoenfeld, David A. Paliwal, Yuvika Shui, Amy Cudkowicz, Merit E. TI The natural history of ALS is changing: Improved survival SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Amyotrophic lateral sclerosis; neuromuscular disease; motor neuron disease; natural history; epidemiology ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; MOTOR-NEURON-DISEASE; III RANDOMIZED-TRIAL; QUALITY-OF-LIFE; CLINICAL-TRIAL; DOUBLE-BLIND; POPULATION; EFFICACY; PENTOXIFYLLINE AB In the past two decades new practice parameters for clinical care in ALS were developed and several clinical trials were performed. We sought to review information in these prospective datasets and assess whether natural history of ALS has changed over time. Survival and the rate of functional decline were compared across the placebo arms of efficacy trials conducted from 1999 to 2005 by the Northeast ALS Consortium (NEALS). Similar data from the placebo arms of 12 other published efficacy ALS trials conducted between 1990 and 2008 were compared descriptively. In the three NEALS clinical trials, survival improved over time in the placebo cohort (p = 0.05) while the rate of change in maximum voluntary isometric contraction (MVIC) (p = 0.15), ALS Functional Rating Scale (ALSFRS) (p = 0.6) and vital capacity (%VC) (p = 0.5) was unchanged. No differences were observed in the mean rates of decline of these outcome measures in the published clinical trials. However, survival improved in the more recently conducted trials. Survival improved over time in placebo controlled participants enrolled in clinical trials in ALS since 1990. However, the decline in measures of function appears unchanged since then. These changes in natural history reflect improvements in symptomatic care of ALS. C1 [Qureshi, Muddasir; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Boston, MA USA. [Qureshi, Muddasir; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Schoenfeld, David A.; Paliwal, Yuvika; Shui, Amy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Biostat Ctr, Boston, MA USA. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, 13th St,Bldg 149,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org FU Northeast ALS (NEALS) Consortium; Digiovanni Fund FX We thank the study participants and the members of the Northeast ALS (NEALS) Consortium. MEC receives support from the Digiovanni Fund. NR 41 TC 29 Z9 29 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 5-6 BP 324 EP 331 DI 10.3109/17482960903009054 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 526MN UT WOS:000272294000009 PM 19922119 ER PT J AU Petrich, W Lewandrowski, KB Muhlestein, JB Hammond, MEH Januzzi, JL Lewandrowski, EL Pearson, RR Dolenko, B Fruh, J Haass, M Hirschl, MM Kohler, W Mischler, R Mocks, J Ordonez-Llanos, J Quarder, O Somorjai, R Staib, A Sylven, C Werner, G Zerback, R AF Petrich, W. Lewandrowski, K. B. Muhlestein, J. B. Hammond, M. E. H. Januzzi, J. L. Lewandrowski, E. L. Pearson, R. R. Dolenko, B. Frueh, J. Haass, M. Hirschl, M. M. Koehler, W. Mischler, R. Moecks, J. Ordonez-Llanos, J. Quarder, O. Somorjai, R. Staib, A. Sylven, C. Werner, G. Zerback, R. TI Potential of mid-infrared spectroscopy to aid the triage of patients with acute chest pain SO ANALYST LA English DT Article; Proceedings Paper CT SPEC 2008 Conference on Shedding Light on Disease - Optical Diagnosis for the New Millenium CY OCT 25-29, 2008 CL Sao Jose dos Campos, BRAZIL ID BOVINE SPONGIFORM ENCEPHALOPATHY; ACUTE CORONARY SYNDROMES; DISEASE PATTERN-RECOGNITION; INFRARED-SPECTROSCOPY; MYOCARDIAL-INFARCTION; RAMAN-SPECTROSCOPY; DIABETES-MELLITUS; WHOLE-BLOOD; HUMAN SERA; SPECTRA AB A total of 1,429 serum samples from 389 consecutive patients with acute chest pain were analyzed with the goal to aid the rapid diagnosis of acute myocardial infarction. To the best of our knowledge this is the largest and most comprehensive study on mid-infrared spectroscopy in cardiology. We were able to identify those signatures in the mid-infrared spectra of the samples, which were specific to either acute myocardial infarction or chest pain of other origin (angina pectoris, oesophagitis, etc). These characteristic spectral differences were used to distinguish between the cause of the donor's acute chest pain using robust linear discriminant analysis. A sensitivity of 88.5% and a specificity of 85.1% were achieved in a blind validation. The area under the receiver operating characteristics curve amounts to 0.921, which is comparable to the performance of routine cardiac laboratory markers within the same study population. The biochemical interpretation of the spectral signatures points towards an important role of carbohydrates and potentially glycation. Our studies indicate that the "Diagnostic Pattern Recognition (DPR)'' method presented here has the potential to aid the diagnostic procedure as early as within the first 6 hours after the onset of chest pain. C1 [Petrich, W.; Frueh, J.; Mischler, R.; Moecks, J.; Quarder, O.; Staib, A.; Werner, G.; Zerback, R.] Roche Diagnost GmbH, D-68305 Mannheim, Germany. [Petrich, W.] Univ Heidelberg, Kirchhoff Inst Phys, D-69120 Heidelberg, Germany. [Lewandrowski, K. B.; Januzzi, J. L.; Lewandrowski, E. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Muhlestein, J. B.; Hammond, M. E. H.; Pearson, R. R.] Latter Day St Hosp, Salt Lake City, UT 84143 USA. [Dolenko, B.; Somorjai, R.] Natl Res Council Canada, Inst Biodiagnost, Winnipeg, MB R3B 1Y6, Canada. [Haass, M.] Univ Klin Heidelberg, D-69120 Heidelberg, Germany. [Hirschl, M. M.] New Gen Hosp, A-1090 Vienna, Austria. [Koehler, W.] Baseline GbR, D-60487 Frankfurt, Germany. [Ordonez-Llanos, J.] Hosp Santa Creu & Sant Pau, Barcelona 08025, Spain. [Sylven, C.] Karolinska Univ Hosp, S-14186 Huddinge, Sweden. RP Petrich, W (reprint author), Roche Diagnost GmbH, Sandhofer Str 116, D-68305 Mannheim, Germany. RI Ordonez-Llanos, Jordi/B-4961-2011; Ordonez-Llanos, Jorge/A-9335-2010 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; NR 34 TC 14 Z9 14 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2009 VL 134 IS 6 BP 1092 EP 1098 DI 10.1039/b820923e PG 7 WC Chemistry, Analytical SC Chemistry GA 450OY UT WOS:000266411900008 PM 19475134 ER PT J AU Cheng, XH Chen, G Rodriguez, WR AF Cheng, Xuanhong Chen, Grace Rodriguez, William R. TI Micro- and nanotechnology for viral detection SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE Viral diagnosis; Bio-MEMS; Nanotechnology ID IMMUNODEFICIENCY-VIRUS TYPE-1; REAL-TIME PCR; MICROFLUIDIC DEVICE; DENGUE VIRUS; ELECTRICAL DETECTION; SENSITIVE DETECTION; LIGHT-SCATTERING; RAPID DETECTION; DNA DETECTION; WHOLE-BLOOD AB Since the identification of viruses at the start of the 20th century, detecting their presence has presented great challenges. In the past two decades, there has been significant progress in viral detection methods for clinical diagnosis and environmental monitoring. The earliest advances were in molecular biology and imaging techniques. Advances in microfabrication and nanotechnology have now begun to play an important role in viral detection, and improving the detection limit, operational simplicity, and cost-effectiveness of viral diagnostics. Here we provide an overview of recent advances, focusing especially on advances in simple, device-based approaches for viral detection. C1 [Rodriguez, William R.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Cheng, Xuanhong] Lehigh Univ, Whitaker Lab, Bethlehem, PA 18015 USA. [Chen, Grace] Massachusetts Gen Hosp, Harvard MIT Hlth Sci & Technol, Charlestown, MA 02119 USA. RP Rodriguez, WR (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM xuc207@lehigh.edu; gracec@mit.edu; wrodriguez@partners.org NR 97 TC 36 Z9 36 U1 2 U2 37 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JAN PY 2009 VL 393 IS 2 BP 487 EP 501 DI 10.1007/s00216-008-2514-x PG 15 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 387FI UT WOS:000261936700014 PM 19052733 ER PT B AU Pomerantz, M Kantoff, P AF Pomerantz, Mark Kantoff, Philip BE Tindall, D Mohler, J TI Clinical Progression to Castration-Recurrent Prostate Cancer SO ANDROGEN ACTION IN PROSTATE CANCER LA English DT Article; Book Chapter ID ANDROGEN DEPRIVATION THERAPY; SURROGATE END-POINT; LEUKEMIA GROUP-B; PHASE-II TRIAL; RADICAL PROSTATECTOMY; HORMONAL-THERAPY; NATURAL-HISTORY; ANTIANDROGEN WITHDRAWAL; TRANSDERMAL ESTRADIOL; RADIATION-THERAPY C1 [Pomerantz, Mark] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Pomerantz, M (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dana Bldg,Room 1230, Boston, MA 02115 USA. EM Mark_Pomerantz@dfci.harvard.edu NR 65 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69177-0 PY 2009 BP 57 EP + DI 10.1007/978-0-387-69179-4_2 D2 10.1007/978-0-387-69179-4 PG 17 WC Andrology; Oncology SC Endocrinology & Metabolism; Oncology GA BKJ91 UT WOS:000268335300003 ER PT B AU Wang, QB Brown, M AF Wang, Qianben Brown, Myles BE Tindall, D Mohler, J TI Mapping the Androgen Receptor Cistrome SO ANDROGEN ACTION IN PROSTATE CANCER LA English DT Article; Book Chapter ID PROSTATE-CANCER CELLS; PROTEIN-PROTEIN INTERACTION; THYROID-HORMONE RECEPTOR; ETS TRANSCRIPTION FACTOR; FACTOR-BINDING-SITES; GENE-EXPRESSION; ESTROGEN-RECEPTOR; GLUCOCORTICOID-RECEPTOR; NUCLEAR RECEPTORS; BREAST-CANCER AB Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in prostate cancer. Mapping the AR cistrome (cis-targets of a transacting factor across the genome) by ChIP-on-chip (chromatin immunoprecipitation on a microarray) discovers that the majority of AR-binding regions is far from the promoters of AR target genes and contains noncanonical AR responsive elements (ARE). Importantly, a noncanonical ARE is served as a cis-regulatory target of AR action in TMPRSS2, a gene fused to ETS transcription factors in the majority of prostate cancers. In addition other DNA sequence motifs are significantly enriched within the AR-binding regions and are bound by cooperating transcription factors FoxA 1, GATA2, Oct1, and ETS1. These transcription factors cooperate in mediating the androgen response and offer potential new opportunities for therapeutic intervention. C1 [Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. EM myles_brown@dfc.harvard.edu OI Brown, Myles/0000-0002-8213-1658 NR 101 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69177-0 PY 2009 BP 663 EP 680 DI 10.1007/978-0-387-69179-4_28 D2 10.1007/978-0-387-69179-4 PG 18 WC Andrology; Oncology SC Endocrinology & Metabolism; Oncology GA BKJ91 UT WOS:000268335300029 ER PT J AU Sewell, JC Raines, DE Eger, EI Laster, MJ Sear, JW AF Sewell, Jason C. Raines, Douglas E. Eger, Edmond I., II Laster, Michael J. Sear, John W. TI A Comparison of the Molecular Bases for N-Methyl-D-Aspartate-Receptor Inhibition Versus Immobilizing Activities of Volatile Aromatic Anesthetics SO ANESTHESIA AND ANALGESIA LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 14-18, 2006 CL Chicago, IL SP Amer Soc Anesthesiologists ID GENERAL-ANESTHETICS; COMFA MODELS; MODULATION; ISOFLURANE; DERIVATION; XENON; QSAR AB BACKGROUND: Aromatic anesthetics exhibit a wide range of N-methyl-D-aspartate We sought to (NMDA) receptor inhibitory potencies and immobilizing activities. characterize the molecular basis of NMDA receptor inhibition using comparative molecular field analysis (CoMFA), and compare the results to those from an equivalent model for immobilizing activity. METHODS: Published potency data for 14 compounds were Supplemented with new values for 2 additional agents. The anesthetics were divided into a training set (n = 4) used to formulate the activity models and a test set (n = 4) used to independently, assess the models' predictive capability. The anesthetic structures were geometry optimized using ab initio quantum mechanics and aligned by field-fit minimization to provide the best correlation between the steric and electrostatic fields Of the Molecules and one or more lead structures. Orientations that yielded CoMFA models with the greatest predictive capability (assessed by leave-one-out cross-validation) were retained. RESULTS: The final CoMFA model for the inhibition of NR1/NR2B NMDA receptors explained 99.3%, of the variance in the observed activities of the 12 training set agents = (F(2,9) = 661.5, P < 0.0001). The model effectively predicted inhibitory potency for the training set (cross-validaed r(2) (CV) = 0.944) and 4 excluded test set compounds (predictive r(2) (Pred) = 0.966). The equivalent model for immobility in response to noxious Stimuli explained 98.0% of the variance in the observed activities for the training set (F(2,9) = 219.2, P < 0.0001) and exhibited adequate predictive capability for both the trainnig set (r(2) (CV) = 0.872) and test set (r(2) (Pred) = 0.926) agents. Comparison of pharmacophoric maps showed that several key steric and electrostatic regions were common to both activity models, but differences were observed in the relative importance of these key regions with respect to the two aspects of anesthetic activity. CONCLUSIONS: The similarities in the pharmacophoric maps are consistent with NMDA receptors contributing part of the immobilizing activity of volatile aromatic anesthetics. C1 [Sewell, Jason C.; Sear, John W.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Anaesthet, Headington, England. [Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Raines, Douglas E.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Eger, Edmond I., II; Laster, Michael J.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. RP Sear, JW (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Anaesthet, Oxford OX3 9DU, England. EM john.sear@nda.ox.ac.uk FU NIGMS NIH HHS [P01 GM058448, 1P01 GM47818, R01 GM061927, P01 GM047818, P01 GM58448] NR 21 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2009 VL 108 IS 1 BP 168 EP 175 DI 10.1213/ane.0b013e31818de158 PG 8 WC Anesthesiology SC Anesthesiology GA 387PB UT WOS:000261963000025 PM 19095845 ER PT J AU Yu, BL Volpato, GP Chang, KQ Bloch, KD Zapol, WM AF Yu, Binglan Volpato, Gian Paolo Chang, Keqin Bloch, Kenneth D. Zapol, Warren M. TI Prevention of the Pulmonary Vasoconstrictor Effects of HBOC-201 in Awake Lambs by Continuously Breathing Nitric Oxide SO ANESTHESIOLOGY LA English DT Article ID CELL-FREE HEMOGLOBIN; HEMORRHAGIC-SHOCK; OXYGEN CARRIERS; BLOOD SUBSTITUTES; PLASMA COMPONENTS; HYPERTENSION; RESUSCITATION; MODEL; NO; TRANSFUSION AB Background: Hemoglobin-based oxygen-carrying solutions (HBOC) provide emergency alternatives to blood transfusion to carry oxygen to tissues without the risks of disease transmission or transfusion reaction. Two primary concerns hampering the clinical acceptance of acellular HBOC are the occurrence of systemic and pulmonary vasoconstriction and the maintenance of the heme-iron in the reduced state (Fe(+2)). We recently demonstrated that pretreatment with inhaled nitric oxide prevents the systemic hypertension Induced by HBOC-201 (polymerized bovine hemoglobin) Infusion in awake mice and sheep without causing methemoglobinemia. However, the impact of HBOC-201 infusion with or without inhaled nitric oxide on pulmonary vascular tone has not yet been examined. Methods: The pulmonary and systemic hemodynamic effects of breathing nitric oxide both before and after the administration of HBOC-201 were determined in healthy, awake lambs. Results: Intravenous administration of HBOC-201 (12 ml/kg) induced prolonged systemic and pulmonary vasoconstriction. Pretreatment with inhaled nitric oxide (80 parts per million [ppm] for 1 h) prevented the HBOC-201-induced increase in mean arterial pressure but not the increase of pulmonary arterial pressure, systemic vascular resistance, or pulmonary vascular resistance. Pretreatment with inhaled nitric oxide (80 ppm for 1 h) followed by breathing a lower concentration of nitric oxide (5 ppm) during and after HBOC-201 infusion prevented systemic and pulmonary vasoconstriction without increasing methemoglobin levels. Conclusions: These findings demonstrate that pretreatment with inhaled nitric oxide followed by breathing a lower concentration of the gas during and after administration of HBOC-201 may enable administration of an acellular hemoglobin substitute without vasoconstriction while preserving its oxygen-carrying capacity. C1 [Yu, Binglan; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Anesthesia Ctr Crit C, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Anesthesia Ctr Crit C, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@partners.org FU National Institutes of Health, Bethesda, Maryland [HL-42397] FX This work was supported by US Public Health Service Grant HL-42397 (Dr. Zapol) from the National Institutes of Health, Bethesda, Maryland. NR 39 TC 23 Z9 25 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2009 VL 110 IS 1 BP 113 EP 122 PG 10 WC Anesthesiology SC Anesthesiology GA 388XD UT WOS:000262052600020 PM 19104178 ER PT J AU Zheng, X Sallum, UW Verma, S Athar, H Evans, CL Hasan, T AF Zheng, Xiang Sallum, Ulysses W. Verma, Sarika Athar, Humra Evans, Conor L. Hasan, Tayyaba TI Exploiting a Bacterial Drug-Resistance Mechanism: A Light-Activated Construct for the Destruction of MRSA SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE drug resistance; lactams; photochemistry; photodynamic therapy; photosensitizers ID PHASE-II TRIAL; PHOTODYNAMIC THERAPY; BETA-LACTAMASE; INHIBITION C1 [Zheng, Xiang; Sallum, Ulysses W.; Verma, Sarika; Athar, Humra; Evans, Conor L.; Hasan, Tayyaba] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zheng, Xiang; Sallum, Ulysses W.; Verma, Sarika; Athar, Humra; Evans, Conor L.; Hasan, Tayyaba] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org RI Zheng, Xiang/C-7757-2009 NR 16 TC 40 Z9 40 U1 1 U2 19 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2009 VL 48 IS 12 BP 2148 EP 2151 DI 10.1002/anie.200804804 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 422FC UT WOS:000264411800020 PM 19206126 ER PT J AU Lee, H Yoon, TJ Weissleder, R AF Lee, Hakho Yoon, Tae-Jong Weissleder, Ralph TI Ultrasensitive Detection of Bacteria Using Core-Shell Nanoparticles and an NMR-Filter System SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE biosensors; microfluidics; nanoparticles; nanotechnology; NMR spectroscopy C1 [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Lee, Hakho; Yoon, Tae-Jong; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM rweissleder@mgh.harvard.edu FU [U01 HL080731] FX We thank D. Hung (MGH) and M. Cima (MIT) for many helpful discussions, R. M. Westervelt (Harvard) for support in device fabrication, and N. Sergeyev (MCH) for synthesizing CLIO. This work was supported by U01 HL080731. NR 19 TC 110 Z9 111 U1 2 U2 41 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2009 VL 48 IS 31 BP 5657 EP 5660 DI 10.1002/anie.200901791 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 477SD UT WOS:000268538100014 PM 19554581 ER PT J AU Devaraj, NK Upadhyay, R Hatin, JB Hilderbrand, SA Weissleder, R AF Devaraj, Neal K. Upadhyay, Rabi Hatin, Jered B. Hilderbrand, Scott A. Weissleder, Ralph TI Fast and Sensitive Pretargeted Labeling of Cancer Cells through a Tetrazine/trans-Cyclooctene Cycloaddition SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE bioorthogonal reactions; cancer; cycloaddition; imaging agents; tetrazines ID GROWTH-FACTOR RECEPTOR; IN-VIVO; CLICK CHEMISTRY; LIVING SYSTEMS; MONOCLONAL-ANTIBODIES; SMALL MOLECULES; AZIDE-ALKYNE; LUNG-CANCER; COPPER-FREE; EXPRESSION C1 [Devaraj, Neal K.; Upadhyay, Rabi; Hatin, Jered B.; Hilderbrand, Scott A.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. RP Hilderbrand, SA (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM scott_hilderbrand@hms.harvard.edu; rweissleder@mgh.harvard.edu RI Devaraj, Neal/B-4712-2014 FU NIH [U01-HL080731, T32-CA79443] FX We thank Dr. Ned Keliher for helpful advice. This research was supported in part by NIH grants U01-HL080731 and T32-CA79443. NR 40 TC 191 Z9 192 U1 5 U2 90 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2009 VL 48 IS 38 BP 7013 EP 7016 DI 10.1002/anie.200903233 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 497KM UT WOS:000270058100011 PM 19697389 ER PT J AU Yan, T Yang, YN Cheng, X DeAngelis, MM Hoh, J Zhang, H AF Yan, T. Yang, Y. -N. Cheng, X. DeAngelis, M. M. Hoh, J. Zhang, H. TI Genotypic Association Analysis Using Discordant-Relative-Pairs SO ANNALS OF HUMAN GENETICS LA English DT Article DE Discordant-relative-pair; association analysis; population stratification; McNemar's test; Cochran-Armitage trend test; maximum efficient robust test; Bhapkar's test ID COMPLEX HUMAN-DISEASES; SIB-TRANSMISSION/DISEQUILIBRIUM-TEST; CASE-CONTROL DESIGNS; LINKAGE DISEQUILIBRIUM; TREND TESTS; POWER AB In practice, family-based design has been widely used in disease-gene association analysis. The major advantage of such design is that it is not subject to spurious association due to population structure such as population stratification (PS) and admixture. A disadvantage is that parental genotypes are hard to obtain if the disease is late onset for which a discordant-relative-pair design is useful. Designs of such kind include full-sib-pair, half-sib-pair, first-cousin-pair, and so on. The closer the relatedness of the pair, the less possible that they are subject to population stratification. On the other hand, the association test using close relative-pairs may be less powerful due to over-matching. Trade-off between these two factors (population structure and over-matching) is the major concern of this study. Some tests, namely McNemar's test, matched Cochran-Armitage trend tests (CATTs), matched maximum efficient robust test (MERT), and Bhapkar's test, are used for testing disease-gene association based on relative-pair designs. These tests are shown to be valid in the presence of PS but not admixture. Numerical studies show that the McNemar's test, additive CATT, MERT, and Bhapkar's test are robust in power, but none of them is uniformly more powerful than the others. In most simulations, the power of any of the tests increases as the pair is more distant. The proposed methods are applied to two real examples. C1 [Yan, T.; Yang, Y. -N.; Cheng, X.; Zhang, H.] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. [DeAngelis, M. M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Hoh, J.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. RP Zhang, H (reprint author), Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. EM zhangh@ustc.edu.cn RI DeAngelis, e/J-7863-2015 FU National Natural Science Foundation of China [10671189, 10701067]; Knowledge Innovation Program of the Chinese Academy of Science FX We are grateful to two reviewers for their helpful comments. This work was supported in part by the National Natural Science Foundation of China (10671189, 10701067), the Knowledge Innovation Program of the Chinese Academy of Science, and the Outstanding Overseas Chinese Scholars Fund of Chinese Academy of Sciences. NR 23 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2009 VL 73 BP 84 EP 94 DI 10.1111/j.1469-1809.2008.00488.x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 390FL UT WOS:000262149600010 PM 19040657 ER PT J AU Marjamaa, A Salomaa, V Newton-Cheh, C Porthan, K Reunanen, A Karanko, H Jula, A Lahermo, P Vaananen, H Toivonen, L Swan, H Viitasalo, M Nieminen, MS Peltonen, L Oikarinen, L Palotie, A Kontula, K AF Marjamaa, Annukka Salomaa, Veikko Newton-Cheh, Christopher Porthan, Kimmo Reunanen, Antti Karanko, Hannu Jula, Antti Lahermo, Paivi Vaananen, Heikki Toivonen, Lauri Swan, Heikki Viitasalo, Matti Nieminen, Markku S. Peltonen, Leena Oikarinen, Lasse Palotie, Aarno Kontula, Kimmo TI High prevalence of four long QT syndrome founder mutations in the Finnish population SO ANNALS OF MEDICINE LA English DT Article DE Epidemiology; ion channels; KCNH2; KCNQ1; long QT syndrome; QT interval ID TORSADES-DE-POINTES; INTERVAL DURATION; CHANNEL MUTATIONS; SYNDROME GENES; REPOLARIZATION; SPECTRUM; IDENTIFICATION; POLYMORPHISMS; ASSOCIATION; VARIANTS AB Aims. Long QT syndrome (LQTS) is an inherited arrhythmia disorder with an estimated prevalence of 0.01%-0.05%. In Finland, four founder mutations constitute up to 70% of the known genetic spectrum of LQTS. In the present survey, we sought to estimate the actual prevalence of the founder mutations and to determine their effect sizes in the general Finnish population. Methods and results. We genotyped 6334 subjects aged30 years from a population cohort (Health 2000 study) for the four Finnish founder mutations using Sequenom MALDI-TOF mass spectrometry. The electrocardiogram (ECG) parameters were measured from digital 12-lead ECGs, and QT intervals were adjusted for age, sex, and heart rate using linear regression. A total of 27 individuals carried one of the founder mutations resulting in their collective prevalence estimate of 0.4% (95% CI 0.3%-0.6%). The KCNQ1 G589D mutation (n=8) was associated with a 50 ms (SE 7.0) prolongation of the adjusted QT interval (P=9.010-13). The KCNH2 R176W variant (n=16) resulted in a 22 ms (SE 4.7) longer adjusted QT interval (P=2.110-6). Conclusion. In Finland 1 individual out of 250 carries a LQTS founder mutation, which is the highest documented prevalence of LQTS mutations that lead to a marked QT prolongation. C1 [Marjamaa, Annukka; Palotie, Aarno; Kontula, Kimmo] Univ Helsinki, Biomedicum Helsinki, Res Program Mol Med, FIN-00290 Helsinki, Finland. [Salomaa, Veikko; Reunanen, Antti; Karanko, Hannu; Jula, Antti; Peltonen, Leena] Natl Publ Hlth Inst, Helsinki, Finland. [Newton-Cheh, Christopher] Broad Inst Harvard, Cambridge, MA USA. [Porthan, Kimmo; Toivonen, Lauri; Swan, Heikki; Viitasalo, Matti; Nieminen, Markku S.; Oikarinen, Lasse] Univ Helsinki, Dept Cardiol, FIN-00290 Helsinki, Finland. [Lahermo, Paivi; Palotie, Aarno] Univ Helsinki, Finnish Genome Ctr, FIN-00290 Helsinki, Finland. [Vaananen, Heikki] Helsinki Univ Technol, Biomed Engn Lab, FIN-02150 Espoo, Finland. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Salomaa, Veikko; Reunanen, Antti; Karanko, Hannu; Jula, Antti; Peltonen, Leena] Univ Helsinki, Biomedicum Helsinki, Dept Med Genet, FIN-00290 Helsinki, Finland. [Palotie, Aarno] Univ Helsinki, Dept Clin Chem, FIN-00290 Helsinki, Finland. [Kontula, Kimmo] Univ Helsinki, Dept Med, FIN-00290 Helsinki, Finland. [Peltonen, Leena; Palotie, Aarno] Program Med & Populat Genet, Wellcome Trust Sanger Inst, Hinxton, England. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Kontula, K (reprint author), Univ Helsinki, Helsinki Univ Hosp, Dept Med, FIN-00290 Helsinki, Finland. EM kimmo.kontula@hus.fi RI Vaananen, Heikki/F-7013-2012 OI Vaananen, Heikki/0000-0001-8649-1047 FU Sigrid Juselius Foundation; Finnish Academy; Center of Excellence of Common Disease Genetics of the Academy of Finland; Finska Lakaresallskapet Foundation; Biomedicum Helsinki Foundation; National Institutes of Health [HL080025]; Doris Duke Charitable Foundation Clinical Scientist Development Award; Burroughs Wellcome Fund Career Award for Medical Scientists; Aarne Koskelo Foundation; Finnish Foundation for Cardiovascular Research; Ida Montin Foundation; Paavo and Eila Salonen Foundation FX Susanna Tverin, Pirkko Alha, Harri Rissanen, Anu Yliperttula, and Sirkka Ekstrom are acknowledged for skilful technical assistance. The study was financially supported by grants from the Sigrid Juselius Foundation and the Finnish Academy to Dr Kontula and by the Center of Excellence of Common Disease Genetics of the Academy of Finland. Dr Marjamaa has received funding from the Finska Lakaresallskapet Foundation and the Biomedicum Helsinki Foundation. Dr Newton-Cheh is supported by the National Institutes of Health (HL080025), a Doris Duke Charitable Foundation Clinical Scientist Development Award, and a Burroughs Wellcome Fund Career Award for Medical Scientists. Dr Porthan has received funding from the Aarne Koskelo Foundation, the Finnish Foundation for Cardiovascular Research, the Ida Montin Foundation, the Paavo and Eila Salonen Foundation. Dr Salomaa was also supported by the Sigrid Juselius Foundation. NR 36 TC 31 Z9 31 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2009 VL 41 IS 3 BP 234 EP U10 AR PII 908024525 DI 10.1080/07853890802668530 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 420EF UT WOS:000264271000008 PM 19160088 ER PT J AU Ali, R Cusi, K AF Ali, Rafeeq Cusi, Kenneth TI New diagnostic and treatment approaches in non-alcoholic fatty liver disease (NAFLD) SO ANNALS OF MEDICINE LA English DT Review DE Fatty liver; insulin resistance; NAFLD; NASH; obesity; thiazolidinediones; type 2 diabetes mellitus ID TYPE-2 DIABETIC-PATIENTS; HEPATIC INSULIN-RESISTANCE; ACTIVATED PROTEIN-KINASE; MAGNETIC-RESONANCE-SPECTROSCOPY; PLACEBO-CONTROLLED TRIAL; SEVERELY OBESE SUBJECTS; LIFE-STYLE MODIFICATION; II RECEPTOR ANTAGONIST; GASTRIC BYPASS-SURGERY; NECROSIS-FACTOR-ALPHA AB Non-alcoholic fatty liver disease or NAFLD is a chronic liver condition characterized by hepatic steatosis and associated with insulin resistance and type 2 diabetes mellitus (T2DM). In many patients fat accumulation leads to steatohepatitis (NASH) with chronic necrosis, inflammation, and fibrosis, and eventually to the development of cirrhosis. Obese and T2DM patients are at the greatest risk for NASH and progressive disease. New diagnostic techniques, such as magnetic resonance imaging and spectroscopy (MRS), have enhanced our way to non-invasively quantify liver fat and suggest that the epidemic of NAFLD is much larger than previously believed. However, the diagnosis of NAFLD for clinicians remains difficult due to a number of factors: limited awareness, non-specific symptoms, few laboratory findings, and the need for a liver biopsy to confirm the diagnosis. Traditional treatment approaches have centered on weight loss, but data are limited on its long-term efficacy, and the overall compliance is poor. Recently, pioglitazone has been shown to be safe and effective in patients with NASH and may radically change our approach to the disease. Still, many aspects remain poorly understood. Taken together, wider use of new diagnostic methods and treatment approaches appears to signal the dawn of a new era in the management of NAFLD. C1 [Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78284 USA. [Ali, Rafeeq] Univ Texas Hlth Sci Ctr San Antonio, Div Endocrinol, San Antonio, TX 78284 USA. [Cusi, Kenneth] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Room 3-380S,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM cusi@uthscsa.edu NR 125 TC 61 Z9 78 U1 0 U2 4 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 EI 1365-2060 J9 ANN MED JI Ann. Med. PY 2009 VL 41 IS 4 BP 265 EP 278 AR PII 907688313 DI 10.1080/07853890802552437 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 434QY UT WOS:000265290400003 PM 19353360 ER PT J AU Sheth, KN Gilson, AJ Chang, YC Kumar, MA Rahman, RM Rost, NS Schwab, K Cortellini, L Goldstein, JN Smith, EE Greenberg, SM Rosand, J AF Sheth, Kevin N. Gilson, Aaron J. Chang, Yuchiao Kumar, Mona A. Rahman, Rosanna M. Rost, Natalia S. Schwab, Kristin Cortellini, Lynelle Goldstein, Joshua N. Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan TI Packed Red Blood Cell Transfusion and Decreased Mortality in Intracerebral Hemorrhage SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 134th Annual Meeting of the American-Neurological-Association CY OCT 11-14, 2009 CL Baltimore, MD SP Amer Neurol Assoc C1 [Sheth, Kevin N.] Univ Maryland, Med Ctr, Dept Neurol, Div Stroke & Neurocrit Care, Baltimore, MD 21201 USA. [Sheth, Kevin N.; Rost, Natalia S.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Sheth, Kevin N.; Rost, Natalia S.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Neurointens Care Serv, Boston, MA 02114 USA. [Gilson, Aaron J.; Rahman, Rosanna M.; Schwab, Kristin; Cortellini, Lynelle; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB T2N 1N4, Canada. [Kumar, Mona A.] Thomas Jefferson Univ Hosp, Dept Neurol, Stroke & Neurocrit Care Div, Philadelphia, PA 19107 USA. RI Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016 OI Smith, Eric/0000-0003-3956-1668; NR 3 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2009 VL 66 BP S81 EP S82 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 506EW UT WOS:000270757700314 ER PT J AU Gao, X Simon, KC Han, JL Schwarzschild, MA Ascherio, A AF Gao, Xiang Simon, Kelly C. Han, Jiali Schwarzschild, Michael A. Ascherio, Alberto TI Genetic Determinants of Hair Color and Parkinson's Disease Risk SO ANNALS OF NEUROLOGY LA English DT Article ID MELANOCORTIN-1 RECEPTOR GENOTYPE; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; NITRIC-OXIDE; SKIN-CANCER; VARIANTS; LEVODOPA; MC1R; POLYMORPHISMS; INFLAMMATION AB Objective: A history of melanoma is associated with increased risks for Parkinson's disease (PD). We examined whether hair color, one of the most important phenotypes of pigmentation and a risk factor for melanoma, was associated with PD risk in the Health Professionals Follow-up Study (HPFS; 1986-2002) and the Nurses' Health Stud), (NHS; 1980-2002). Methods: We included 38,641 men and 93,661 women who were free of PD at baseline. Information on natural hair color in early adulthood (age 18-21 years) was assessed via a questionnaire. We also conducted a case-control study (298 PD cases) nested in these two cohorts to examine the association between the melanocortin] -receptor Arg151Cys polymorphism and PD risk. Relative risks (RRs) were estimated using Cox proportional hazards models in the cohort analyses and conditional logistic regression in the nested case-control study. Results: PD risk increased with decreasing darkness of hair color. Pooled RRs for PD were I (reference), 1.40, 1.61, and 1.93 (95% confidence interval, 1.1-3.4) for black, brown, blond, and red hair, respectively, after adjusting for age, smoking, ethnicity, and other covariates. The associations between hair color and PD were particularly strong for relative younger onset of PD (< 70 yr) (adjusted RR for red vs black hair = 3.83; 95% confidence interval, 1.7-8.7). In the case-control study, participants with Cys/Cys genotype, which was associated with red hair, had a greater PD risk, relative to the Arg/Arg genotype (adjusted RR, 3.15; 95% confidence interval, 1.1-9.4). Interpretation: These findings suggest a potential role of pigmentation in PD. C1 [Gao, Xiang; Simon, Kelly C.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Han, Jiali; Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Gao, X (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM xgao@hsph.harvard.edu FU NIH [R01 NS048517]; Parkinson Study Group Mentored Clinical Research Award FX The study was supported by the NIH (National Institute of Neurological Diseases and Stroke, R01 NS048517) and the Parkinson Study Group Mentored Clinical Research Award. NR 51 TC 54 Z9 54 U1 0 U2 6 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 JAN PY 2009 VL 65 IS 1 BP 76 EP 82 DI 10.1002/ana.21535 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 404BD UT WOS:000263124800012 PM 19194882 ER PT J AU Garvey, WT AF Garvey, W. Timothy TI NUTRITION AND CONTROL OF DIABETES IN HOSPITALIZED PATIENTS SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Garvey, W. Timothy] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 57 EP 57 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827200211 ER PT J AU Cho, E Lee, JE Rimm, EB Fuchs, C Giovannucci, EL AF Cho, Eunyoung Lee, Jung Eun Rimm, Eric B. Fuchs, Charles Giovannucci, Edward L. TI PROSPECTIVE STUDY OF ALCOHOL CONSUMPTION AND COLON CANCER RISK BY FAMILY HISTORY OF COLORECTAL CANCER SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Cho, Eunyoung; Lee, Jung Eun; Rimm, Eric B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 81 EP 81 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827200299 ER PT J AU Shen, LR Lai, CQ Li, D Ordovas, JM Kang, JX AF Shen, Li R. Lai, Chao Q. Li, Duo Ordovas, Jose M. Kang, Jing X. TI DROSOPHILA LACKS C20 AND C22 POLYUNSATURATED FATTY ACIDS SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Shen, Li R.; Li, Duo] Zhejiang Univ, Hangzhou 310003, Zhejiang, Peoples R China. [Lai, Chao Q.] Tufts Univ, JM USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Kang, Jing X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 452 EP 452 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827201793 ER PT J AU Yoon, H Powell, M Gibson, M Montgomery, E Hafez, M Liu, G Diasio, R Forastiere, A Benson, A Kleinberg, L Murphy, K AF Yoon, H. Powell, M. Gibson, M. Montgomery, E. Hafez, M. Liu, G. Diasio, R. Forastiere, A. Benson, A. Kleinberg, L. Murphy, K. TI PREDICTION OF TOXICITY BASED ON SINGLE NUCLEOTIDE POLYMORPHISMS (SNP) IN CISPLATIN (C) AND RADIATION (RT) PATHS: RESULTS FROM THE EASTERN COOPERATIVE ONCOLOGY GROUP SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th World Congress on Gastrointestinal Cancer CY JUN 24-27, 2009 CL Barcelona, SPAIN C1 [Yoon, H.; Diasio, R.] Mayo Clin, Rochester, MN USA. [Powell, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gibson, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Montgomery, E.; Hafez, M.; Forastiere, A.; Kleinberg, L.; Murphy, K.] Johns Hopkins Univ, Baltimore, MD USA. [Liu, G.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Benson, A.] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2009 VL 20 BP 11 EP 11 PG 1 WC Oncology SC Oncology GA 473CP UT WOS:000268183100016 ER PT J AU Scott, AR Chong, PST Brigger, MT Randolph, GW Hartnick, CJ AF Scott, Andrew R. Chong, Peter Slao Tick Brigger, Matthew T. Randolph, Gregory W. Hartnick, Christopher J. TI Serial Electromyography of the Thyroarytenoid Muscles Using the NIM-Response System in a Canine Model of Vocal Fold Paralysis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE laryngeal electromyography; recurrent laryngeal nerve; vocal fold paralysis ID LARYNGEAL ELECTROMYOGRAPHY; CORD PARALYSIS; CHILDREN; MANAGEMENT; IMMOBILITY AB Objectives: We sought to determine whether serial intraoperative laryngeal electromyography (L-EMG) or evoked L-EMG predicts vocal fold (VF) recovery following iatrogenic injury. Methods: Six beagles were sedated, and bipolar needle electrodes were inserted into each thyroarytenoid (TA) muscle. Endotracheal tube surface electrodes were also placed. As the sedation lightened, L-EMG activity was recorded from all electrodes with an intraoperative nerve monitoring system. The neck was opened, and direct recurrent laryngeal nerve (RLN) stimulation was performed. Subsequently, 4 animals underwent crush injury of the left RLN, and 2 animals underwent nerve transection. The L-EMG procedures were repeated every I to 2 weeks until left VF motion was observed in the dogs that suffered RLN crush injury. At each time point, the neck was opened and both RLNs were stimulated. Results: Fibrillation potentials were detected in all animals after RLN injury. A change to electrical silence was seen in the animals in the crush injury group that were evaluated during the week preceding VF recovery. Fibrillation potentials and VF immobility persisted in the transection group throughout the complete time course of these experiments. The first appearance of an evoked response coincided with or occurred after the return of left VF motion in the crush injury group. The threshold, latency, and amplitude differed from those of the controls and approached normal values over time. No response was detected in the transected nerves. Conclusions: The disappearance of fibrillations on intraoperative L-EMG was noted in the animals tested the week before the return of VF motion, and the return of motor unit action potentials was seen along with return of VF function. Evoked L-EMG was not helpful in predicting the return of VF mobility, but it may help quantify degrees of RLN injury and predict the speed of recovery. C1 [Scott, Andrew R.; Brigger, Matthew T.; Randolph, Gregory W.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Chong, Peter Slao Tick] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 10 Z9 10 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2009 VL 118 IS 1 BP 56 EP 66 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 399HT UT WOS:000262791700010 PM 19244965 ER PT J AU Yang, K Zhuo, HJ Guglielmo, BJ Wiener-Kronish, J AF Yang, Katherine Zhuo, Hanjing Guglielmo, B. Joseph Wiener-Kronish, Jeanine TI Multidrug-Resistant Pseudomonas aeruginosa Ventilator-Associated Pneumonia: The Role of Endotracheal Aspirate Surveillance Cultures SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE antibiotics; multidrug resistance; Pseudomonas aeruginosa; ventilator-associated pneumonia ID INTENSIVE-CARE-UNIT; NOSOCOMIAL PNEUMONIA; EARLY-ONSET; ANTIBIOTIC-TREATMENT; MANAGEMENT; INFECTIONS; MORTALITY; BACTERIA; OUTCOMES AB BACKGROUND: Inappropriate antibacterial treatment of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) pathogens is associated with increased mortality. Endotracheal aspirate (ETA) surveillance cultures potentially identify MDR pathogens, particularly MDR Pseudomonas aeruginosa, resulting in improved selection of therapy in patients who subsequently develop VAP. OBJECTIVE: To investigate the role of ETA surveillance cultures in the identification of MDR P aeruginosa in newly intubated adults who subsequently develop VAP. METHODS: Daily ETA surveillance cultures for P aeruginosa were collected in all adults newly intubated for 48 hours or more. Patients with preexisting lung disease or colonization or infection with R aeruginosa were excluded. Risk factors and outcomes of patients newly colonized with MDR P aeruginosa were assessed. RESULTS: Seventy-five patents newly colonized with R aeruginosa were identified. Twenty (27%) of these patients were colonized with a P aeruginosa isolate that was MDR (resistant to 0 classes of antibiotics). Six patients were colonized by an isolate resistant to all tested classes of antibiotics. Forty-five percent of patients colonized with MDR P aeruginosa subsequently developed VAP. Prior receipt of fluoroquinolones was an independent predictor of colonization with MDR P aeruginosa (OR 11.82; 95% CI 2.10 to 66.46; p = 0.005). CONCLUSIONS: Performance of routine surveillance cultures may aid in the early detection of MDR P aeruginosa, improving the initiation of early and appropriate antibiotic therapy for patients who subsequently develop VAP. C1 [Yang, Katherine; Guglielmo, B. Joseph] Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, San Francisco, CA 94143 USA. [Zhuo, Hanjing] Univ Calif San Francisco, Sch Med, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Wiener-Kronish, Jeanine] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Yang, K (reprint author), Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, 521 Parnassus Ave,Room C-152, San Francisco, CA 94143 USA. EM yangk@pharmacy.ucsf.edu FU National Center for Research Resources (NCRR) [KL2 RR024130]; [PH 50HL74005]; [HL69809] FX The project described was supported by grant number KL2 RR024130 from the National Center for Research Resources (NCRR) (Dr. Yang) and grant numbers PH 50HL74005 and HL69809 (Drs. Wiener-Kronish and Zhuo). NR 25 TC 22 Z9 25 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 2009 VL 43 IS 1 BP 28 EP 35 DI 10.1345/aph.1L210 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396JR UT WOS:000262588500003 PM 19033484 ER PT J AU Bilimoria, KY Bentrem, DJ Wayne, JD Ko, CY Bennett, CL Talamonti, MS AF Bilimoria, Karl Y. Bentrem, David J. Wayne, Jeffrey D. Ko, Clifford Y. Bennett, Chales L. Talamonti, Mark S. TI Small Bowel Cancer in the United States Changes in Epidemiology, Treatment, and Survival Over the Lost 20 Years SO ANNALS OF SURGERY LA English DT Article ID CARCINOID-TUMORS; CLINICAL CHARACTERISTICS; REGISTRY; METASTASES; RESECTION; QUALITY; LIVER AB Background: Previous Studies have shown an increasing incidence of small bowel tumors in the United States. Our objective was to assess this increase by examining changes in histology-specific incidence, treatment, and survival. Methods: Patients with small bowel malignancies were identified front the National Cancer Data Base (NCDB, 1985-2005) and the Surveillance Epidemiology and End Results (SEER, 1973-2004) database. Age-adjusted incidence rates were calculated using SEER. Treatment and survival trends over time were examined using the National Cancer Data Base. Regression models were developed to assess survival over time. Results: Sixty-seven thousand eight hundred forty-three patients were identified with small bowel malignancies: 37.4% carcinoid, 36.9% adenocarcinomas, 8.4% stromal tumors, and 17.3% lymphomas. From 1973 to 2004, the incidence of carcinoid tumors increased more than 4-fold (2.1 to 9.3 per million), whereas changes in adenocarcinomas, stromal tumors, and lymphomas were less pronounced. From 1985 to 2005, utilization of surgery increased significantly for carcinoid tumors from 78.8% to 87.4% (P < 0.0001). Adjuvant chemotherapy utilization for adenocarcinoma increased from 8.1 % in 1985 to 23.8% in 2005 (P < 0.0001). Treatment over time was generally unchanged for lymphoma and stromal tumors. Five-year survival after resection remained unchanged overtime for all histologic subtypes even after adjusting for changes in patient demographics, tumor characteristics, and treatment approaches. Conclusions: The overall incidence of small intestine malignancies has increased considerably, primarily because of carcinoid rumors which are now the most common small bowel cancer. With current treatments, Survival has remained relatively unchanged over the last 20 years. Novel therapeutic options need to be investigated. C1 [Bilimoria, Karl Y.; Ko, Clifford Y.] Northwestern Univ, Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Bentrem, David J.; Wayne, Jeffrey D.; Talamonti, Mark S.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bennett, Chales L.] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Talamonti, Mark S.] Evanston NW Healthcare, Dept Surg, Chicago, IL USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Amer Coll Surg, Canc Programs, 633 N St Clair St,25th Floor, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu FU American Cancer Society [IRG 93-037-12] FX The National Cancer Data Base is supported by the American College of Surgeons, the Commission on Cancer, and the American Cancer Society. Supported by the American College of Surgeons Clinical Scholars in Residence (to K.Y.B.) and a grant from the American Cancer Society (ACS IRG 93-037-12) (to D.J.13.). NR 34 TC 148 Z9 161 U1 1 U2 7 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 JAN PY 2009 VL 249 IS 1 BP 63 EP 71 DI 10.1097/SLA.0b013e31818c4641 PG 9 WC Surgery SC Surgery GA 391FN UT WOS:000262219300011 PM 19106677 ER PT J AU Keck, T Marjanovic, G Fernandez-del Castillo, C Makowiec, F Schafer, AO Rodriguez, JR Razo, O Hopt, UT Warshaw, AL AF Keck, Tobias Marjanovic, Goran Fernandez-del Castillo, Carlos Makowiec, Frank Schaefer, Arndt Oliver Rodriguez, J. Ruben Razo, Oswaldo Hopt, Ulrich Theodor Warshaw, Andrew L. TI The Inflammatory Pancreatic Head Mass Significant Differences in the Anatomic Pathology of German and American Patients With Chronic Pancreatitis Determine Very Different Surgical Strategies SO ANNALS OF SURGERY LA English DT Article ID PYLORUS-PRESERVING PANCREATICODUODENECTOMY; TERM-FOLLOW-UP; RANDOMIZED-TRIAL; LONG-TERM; PORTAL-HYPERTENSION; NATURAL COURSE; RESECTION; DRAINAGE; PAIN; GUIDELINES AB Background: The indications for surgery and the Surgical strategy selected for chronic pancreatitis (CP) vary widely, perhaps because of unaccounted characteristics of different patient populations such as the "inflammatory mass" in the head of the pancreas, commonly described in Europe but not in America. Methods: We compared the pancreatic morphology, anatomic complications, indications leading to intervention, and the operation performed in 93 consecutive patients with CP operated upon either at a German (n = 48) or an American (n = 45) center specializing in pancreatic surgery. Pretreatment computed tomography/magnetic resonance imaging scans were reevaluated by 2 independent radiologists, especially to measure the anterior-posterior diameter of the pancreatic head (the inflammatory mass). Results: The prevalence of endocrine and exocrine insufficiency was not significantly different. The median diameter of the pancreatic head mass was significantly larger in the German group (4.5 vs. 2.6 cm, P < 0.001). Inflammatory mass-dependent symptoms [gastric outlet obstruction (9/48 vs. 1/45: P = 0.02) and hemorrhage (7/48 vs. 0/45; P = 0.013)] were more frequent in the German group. Bile duct stenosis (19/48 vs. 11/43; P = 0.18) and suspicion of malignancy (5/48 vs. 11/43; P = 0.10) were comparable, whereas chronic pain (15/48 vs. 28/43; P = 0.001) was a more frequent indication for surgery in the US group. Splenic or portal vein thrombosis was found only in the German group. The duration of nonoperative therapy was significantly longer in the German group (median 56 vs. 26 months; P = 0.02). In the US group, a pancreatoduodenectomy with antrectomy was performed in most (89%) cases, whereas in the German group a duodenum-preserving head resection was preferred in more than half (25/47) of the cases (P < 0.001). Conclusions: Symptoms, duration of conservative therapy, and selection of surgical treatment all differed significantly between German and American patients with CP. These differences seem to be dependent upon surprising but unexplained disparities in the pathologic pancreatic anatomy between the 2 Populations. C1 [Fernandez-del Castillo, Carlos; Rodriguez, J. Ruben; Razo, Oswaldo; Warshaw, Andrew L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Keck, Tobias; Marjanovic, Goran; Makowiec, Frank; Schaefer, Arndt Oliver; Hopt, Ulrich Theodor] Univ Freiburg, Dept Surg, D-7800 Freiburg, Germany. [Keck, Tobias; Marjanovic, Goran; Makowiec, Frank; Schaefer, Arndt Oliver; Hopt, Ulrich Theodor] Univ Freiburg, Dept Radiol, D-7800 Freiburg, Germany. RP Warshaw, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St WHT 506, Boston, MA 02114 USA. EM awarshaw@partners.org NR 40 TC 25 Z9 34 U1 0 U2 1 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 JAN PY 2009 VL 249 IS 1 BP 105 EP 110 DI 10.1097/SLA.0b013e31818ef078 PG 6 WC Surgery SC Surgery GA 391FN UT WOS:000262219300018 PM 19106684 ER PT J AU Nathan, H Aloia, TA Vauthey, JN Abdalla, EK Zhu, AX Schulick, RD Choti, MA Pawlik, TM AF Nathan, Hari Aloia, Thomas A. Vauthey, Jean-Nicolas Abdalla, Eddie K. Zhu, Andrew X. Schulick, Richard D. Choti, Michael A. Pawlik, Timothy M. TI A Proposed Staging System for Intrahepatic Cholangiocarcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol ID FACTORS INFLUENCING SURVIVAL; MASS-FORMING TYPE; SURGICAL-TREATMENT; LIVER-CANCER; PERIPHERAL CHOLANGIOCARCINOMA; HEPATOCELLULAR-CARCINOMA; PROGNOSTIC-FACTORS; THAILAND; OUTCOMES; MODELS AB The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for liver cancer is based on data exclusively derived from hepatocellular carcinoma (HCC) patients and thus may be inappropriate for patients with intrahepatic cholangiocarcinoma (ICC). We sought to empirically derive an ICC staging system from population-based data on patients with ICC. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 598 patients who underwent surgery for ICC between 1988 and 2004. The discriminative abilities of the AJCC/UICC liver cancer and two Japanese ICC staging systems were evaluated. Independent predictors of survival were identified using Cox proportional hazards models. A staging system for ICC was then derived based on these analyses. The AJCC/UICC T classification system failed to adequately stratify the T2 and T3 cohorts due to tumor size > 5 cm not being a relevant prognostic factor [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.72-1.30]. In contrast, presence of multiple lesions (HR 1.42, 95% CI 1.01-2.01) or vascular invasion (HR 1.53, 95% CI 1.10-2.12) predicted adverse prognosis. Based on these findings, an ICC staging system was developed that omits tumor size. This system showed no loss of prognostic discrimination compared with the AJCC/UICC system and significant superiority over the Japanese systems. We conclude that the AJCC/UICC liver cancer staging system fails to stratify ICC patients adequately and inappropriately includes tumor size. We propose a staging system specifically developed for ICC based on number of tumors, vascular invasion, lymph node status, and presence of metastatic disease. C1 [Nathan, Hari; Schulick, Richard D.; Choti, Michael A.; Pawlik, Timothy M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Aloia, Thomas A.] Methodist Hosp, Dept Surg, Houston, TX 77030 USA. [Vauthey, Jean-Nicolas; Abdalla, Eddie K.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Nathan, H (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. EM tpawlik1@jhmi.edu RI Nathan, Hari/A-2676-2009 FU NCI NIH HHS [P30 CA016672]; NCRR NIH HHS [1KL2RR025006-01] NR 38 TC 115 Z9 127 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2009 VL 16 IS 1 BP 14 EP 22 DI 10.1245/s10434-008-0180-z PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 395WU UT WOS:000262555000003 PM 18987916 ER PT J AU Ligibel, JA Partridge, A Giobbie-Hurder, A Golshan, M Emmons, K Winer, EP AF Ligibel, Jennifer A. Partridge, Ann Giobbie-Hurder, Anita Golshan, Mehra Emmons, Karen Winer, Eric P. TI Physical Activity Behaviors in Women with Newly Diagnosed Ductal Carcinoma-In-Situ SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID INTRADUCTAL BREAST-CANCER; RECEIVING ADJUVANT CHEMOTHERAPY; 10-YEAR FOLLOW-UP; WEIGHT-GAIN; RADIATION-THERAPY; RISK-FACTORS; PATTERNS; SURVIVAL; LIFE; LUMPECTOMY AB Epidemiological evidence suggests that physical activity may affect breast cancer risk and other health outcomes. Little information is available regarding changes in activity after diagnosis and treatment of in-situ cancer. We enrolled 487 women with newly diagnosed ductal carcinoma-in-situ (DCIS) in a longitudinal cohort study. Exercise behaviors were assessed at enrollment and at 18 months. Changes in exercise frequency over time were compared, and the impact of demographic and treatment-related variables was evaluated. Enrollment and 18-month exercise data were available for 391 women (80%). At enrollment, most women performed strenuous physical activity infrequently, and only half engaged in any type of exercise more than twice a week. Overall activity patterns did not change greatly over the course of the study. However, logistic regression modeling of changes in exercise revealed that women who underwent unilateral or bilateral mastectomy (hazard ratio [HR], 2.4; 95% confidence interval [95% CI], 1.3-4.4) and those who were anxious at enrollment (HR, 2.1; 95% CI, 1.1-4.1) were statistically significantly more likely to decrease exercise levels, and women who worked were significantly more likely to increase exercise over the course of the study (HR, 1.9; 95% CI, 1.1-3.3). Nonsignificant variables included age, reconstructive surgery, depressive symptoms, financial status, education, and tamoxifen use. A large proportion of women with newly diagnosed DCIS were inactive and remained so over time. Women who underwent mastectomy, as well as women who were more anxious, were more likely to decrease their level of physical activity. Women with DCIS might benefit from targeted interventions to increase physical activity. C1 [Ligibel, Jennifer A.; Partridge, Ann; Giobbie-Hurder, Anita; Golshan, Mehra; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Ligibel, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jligibel@partners.org FU Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer [5 P50 CA89393-03] FX This research was supported in part by the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer ( 5 P50 CA89393-03). NR 41 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2009 VL 16 IS 1 BP 106 EP 112 DI 10.1245/s10434-008-0174-x PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 395WU UT WOS:000262555000014 PM 18953612 ER PT J AU Merkel, PA Cuthbertson, DD Hellmich, B Hoffman, GS Jayne, DRW Kallenberg, CGM Krischer, JP Luqmani, R Mahr, AD Matteson, EL Specks, U AF Merkel, P. A. Cuthbertson, D. D. Hellmich, B. Hoffman, G. S. Jayne, D. R. W. Kallenberg, C. G. M. Krischer, J. P. Luqmani, R. Mahr, A. D. Matteson, E. L. Specks, U. CA J H Stone Vasculitis Clin Res Cons TI Comparison of disease activity measures for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID WEGENERS-GRANULOMATOSIS; MICROSCOPIC POLYANGIITIS; POLYARTERITIS-NODOSA; RANDOMIZED-TRIAL; ACTIVITY SCORE; CYCLOPHOSPHAMIDE; THERAPY; INDEX AB Aim: Currently, several different instruments are used to measure disease activity and extent in clinical trials of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, leading to division among investigative groups and difficulty comparing study results. An exercise comparing six different vasculitis instruments was performed. Methods: A total of 10 experienced vasculitis investigators from 5 countries scored 20 cases in the literature of Wegener granulomatosis or microscopic polyangiitis using 6 disease assessment tools: the Birmingham Vasculitis Activity Score (BVAS), The BVAS for Wegener granulomatosis (BVAS/WG), BVAS 2003, a Physician Global Assessment (PGA), the Disease Extent Index (DEI) and the Five Factor Score (FFS). Five cases were rescored by all raters. Results: Reliability of the measures was extremely high (intraclass correlations for the six measures all = 0.98). Within each instrument, there were no significant differences or outliers among the scores from the 10 investigators. Test/retest reliability was high for each measure: range = 0.77 to 0.95. The scores of the five acute activity measures correlated extremely well with one another. Conclusions: Currently available tools for measuring disease extent and activity in ANCA-associated vasculitis are highly correlated and reliable. These results provide investigators with confidence to compare different clinical trial data and helps form common ground as international research groups develop new, improved and universally accepted vasculitis disease assessment instruments. C1 [Merkel, P. A.] Boston Univ, Sch Med, Vasculitis Ctr, Boston, MA 02118 USA. [Cuthbertson, D. D.; Krischer, J. P.] Univ S Florida, Tampa, FL USA. [Hellmich, B.] Kreiskrankenhaus Plochingen, Plochingen, Germany. [Hoffman, G. S.] Cleveland Clin, Cleveland, OH 44106 USA. [Jayne, D. R. W.] Addenbrookes Hosp, Cambridge, England. [Kallenberg, C. G. M.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Luqmani, R.] Univ Oxford, Oxford, England. [Mahr, A. D.] Hosp Cochin, Paris, France. [Matteson, E. L.; Specks, U.] Mayo Clin, Rochester, MN USA. [J H Stone Vasculitis Clin Res Cons] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Merkel, PA (reprint author), Boston Univ, Sch Med, Vasculitis Ctr, E5,72 E Concord St, Boston, MA 02118 USA. EM pmerkel@bu.edu OI Luqmani, Raashid/0000-0002-4446-5841 FU National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [U01 AR51874]; the National Center for Research Resources/NIH; Mid-Career Development Awards (NIH/NIAMS) [K24 AR02224, AR047578, AR049185]; [U54 RR01949703] FX Grants were received from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01 AR51874) and the National Center for Research Resources/NIH: U54 RR01949703. The Vasculitis Clinical Research Consortium is part of the NIH Rare Diseases Clinical Research Network (http://www.rarediseasesnetwork.org/vcrc). PAM, ELM and JHS were supported by Mid-Career Development Awards in Clinical Investigation (NIH-NIAMS: K24 AR02224, AR047578 and AR049185). None of the funding sources for this study had any role in any aspect of conducting this research, drafting the manuscript, or the decision to publish the data. NR 12 TC 31 Z9 31 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2009 VL 68 IS 1 BP 103 EP 106 DI 10.1136/ard.2008.097758 PG 4 WC Rheumatology SC Rheumatology GA 384PD UT WOS:000261755800018 PM 18664546 ER PT J AU Rousou, LJ Taylor, KB Lu, XG Healey, N Crittenden, MD Khuri, SF Thatte, HS AF Rousou, Laki J. Taylor, Kristin B. Lu, Xiu-Gui Healey, Nancy Crittenden, Michael D. Khuri, Shukri F. Thatte, Hemant S. TI Saphenous Vein Conduits Harvested by Endoscopic Technique Exhibit Structural and Functional Damage SO ANNALS OF THORACIC SURGERY LA English DT Article ID GRAFT FAILURE; RANDOMIZED-TRIAL; SURGERY; PRESERVATION; PREVENTION; INJURY; PATHOPHYSIOLOGY; ENDOTHELIUM; DYSFUNCTION; INTEGRITY AB Background. Injury to the saphenous vein endothelium during harvest impacts patency after coronary artery bypass graft surgery. Many centers are adopting endoscopic saphenous vein harvest (ESVH) instead of using the traditional open saphenous vein harvest (OSVH) technique. Our objective was to compare the effects of ESVH and OSVH on the structural and functional viability of saphenous vein endothelium using multiphoton imaging, immunofluorescence, and biochemical techniques. Methods. Ten patients scheduled for coronary artery bypass graft surgery were prospectively identified. Each underwent ESVH for one portion and OSVH for another portion of the saphenous vein. A 1-cm segment from each portion was immediately transported to the laboratory for processing. The vessel segments were labeled with fluorescent markers to quantify cell viability (esterase activity), calcium mobilization, and generation of nitric oxide. Samples were also labeled with immunofluorescent antibodies to visualize caveolin, endothelial nitric oxide synthase, von Willebrand factor, and cadherin, and extracted to identify these proteins using Western blot techniques. All labeling, imaging, and image analysis was done in a blinded fashion. Results. Esterase activity was significantly higher in the OSVH group (p < 0.0001). Similarly, calcium mobilization and nitric oxide production were significantly greater in the OSVH group (p = 0.0209, p < 0.0001, respectively). Immunofluoresence and Western blot techniques demonstrated an abnormal alteration in distribution of caveolin and endothelial nitric oxide synthase in the ESVH group. Conclusions. Our study indicates that ESVH has a detrimental effect on the saphenous vein endothelium, which may lead to decreased graft patency and worse patient outcomes. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. [Thatte, Hemant S.] Harvard Univ, Div Cardiothorac Surg, Beth Israel Deaconess Med Ctr,Surg Serv 112, VA Boston Healthcare Syst,Med Sch, Boston, MA 02132 USA. RP Thatte, HS (reprint author), Harvard Univ, Div Cardiothorac Surg, Beth Israel Deaconess Med Ctr,Surg Serv 112, VA Boston Healthcare Syst,Med Sch, 1400 VFW Pkwy, Boston, MA 02132 USA. EM hemant_thatte@hms.harvard.edu FU VA Merit Review; DoD/ONR; NIH Training FX This work was supported by grants from the VA Merit Review (S. F. K.) and DoD/ONR (H. S. T.). Doctor Laki Rousou was supported by a T32 NIH Training Grant for surgical research fellows. NR 38 TC 52 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2009 VL 87 IS 1 BP 62 EP 70 DI 10.1016/j.athoracsur.2008.08.049 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 385SN UT WOS:000261834000012 PM 19101270 ER PT J AU Nehra, D Liberman, M Vagefi, PA Evans, N Inglessis, I Kradin, RL Ono, J Kanarek, DJ Gaissert, HA AF Nehra, Deepika Liberman, Moishe Vagefi, Parsia A. Evans, Nathaniel Inglessis, Ignacio Kradin, Richard L. Ono, Jill Kanarek, David J. Gaissert, Henning A. TI Complete Pulmonary Venous Occlusion After Radiofrequency Ablation for Atrial Fibrillation SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID STENOSIS COMPLICATING ABLATION; VEIN STENOSIS; CATHETER ABLATION; MANAGEMENT AB Pulmonary vein stenosis is a known, yet under-recognized complication of radiofrequency ablation for atrial fibrillation. We present the case of a patient developing complete left-sided pulmonary venous occlusion following radiofrequency ablation. Recommendations are made to allow earlier diagnosis of this complication. C1 [Gaissert, Henning A.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Pulm Med, Boston, MA 02114 USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org RI Evans, Nathaniel/I-2255-2013 OI Evans, Nathaniel/0000-0001-5767-6907 NR 7 TC 9 Z9 9 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 JAN PY 2009 VL 87 IS 1 BP 292 EP 295 DI 10.1016/j.athoracsur.2008.06.060 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 385SN UT WOS:000261834000065 PM 19101316 ER PT J AU Hua, HT Albadawi, H Entabi, F Conrad, MF Stoner, MC Houser, S Watkins, MT AF Hua, Hong T. Albadawi, Hassan Entabi, Fateh Conrad, Mark F. Stoner, Michael C. Houser, Stuart Watkins, Michael T. TI Effects of Acute Global Venous Obstruction and Unfractionated Heparin on Muscle Cytokine Synthesis SO ANNALS OF VASCULAR SURGERY LA English DT Article ID PHLEGMASIA-CERULEA-DOLENS; CATHETER-DIRECTED THROMBOLYSIS; ISCHEMIA-REPERFUSION; SKELETAL-MUSCLE; THROMBOSIS; INFLAMMATION; MICE; ARTERIAL; MODEL; INTERLEUKIN-8 AB Phlegmasia cerulea dolens is a devastating complication of massive deep venous thrombosis, which is clinically characterized by massive lower extremity tissue edema and subsequent arterial insufficiency. These experiments evaluated the local tissue effects of acute global venous obstruction combined with partial arterial ischemia. Experiments were performed to assess the effects of heparin on the cytokine response to simultaneous venous and partial arterial obstruction. Murine hind limbs were subjected to conditions of unilateral venous occlusion and partial tourniquet limb ischemia, which was confirmed by laser Doppler imaging (LDI). Mice underwent either hind limb venous obstruction with intravenous unfractionated heparin (200 IU/kg) or intravenous saline 5 min before venous occlusion. Sham-treated mice were subjected to anesthesia alone without venous occlusion. After 3 hr, the mice were killed and tissue was harvested for measurement of edema (wet to dry weight ratio, W/D), muscle viability, indices of local thrombosis (thrombin-antithrombin complex [TAT]), and cytokine analysis for growth-related oncogene-1 (GRO-1) and interleukin-6 (IL-6, protein via enzyme-linked immunoassay and mRNA via reverse transcriptase polymerase chain reaction). Bleeding time and volume were documented in saline-and heparin-treated mice to confirm systemic anticoagulation. Administration of intravenous heparin resulted in a marked increase in bleeding time and volume. LDI confirmed venous obstruction and ongoing arterial inflow. Venous obstruction resulted in severe visible edema that correlated with a significantly higher W/D ratio but was not associated with a significant decrease in muscle viability. GRO-1 and IL-6 protein and mRNA levels were significantly elevated in the venous occlusion group compared to sham. Heparin therapy significantly decreased TAT3 levels but did not alter the pro. le of GRO-1 or IL-6 protein levels seen with venous occlusion. Venous occlusion with partial ischemia induces a unique and potent local cytokine expression. Heparin therapy did not ameliorate the cytokine response. These data indicate that heparin therapy does not modulate the cytokine response to venous obstruction. C1 [Hua, Hong T.; Albadawi, Hassan; Entabi, Fateh; Conrad, Mark F.; Stoner, Michael C.; Watkins, Michael T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Houser, Stuart; Watkins, Michael T.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Watkins, Michael T.] VA Boston Healthcare Syst, Boston, MA USA. RP Watkins, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Vasc & Endovasc Surg, 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM mtwatkins@partners.org FU Research Service of the Veterans Administration; VA Department of Defense Combat Casualty Care Project; Department of Surgery; Division of Vascular and Endovascular Surgery, Massachusetts General Hospital FX Funding for these studies was provided by a Merit Award from the Research Service of the Veterans Administration, the VA Department of Defense Combat Casualty Care Project, the Department of Surgery, and the Division of Vascular and Endovascular Surgery, Massachusetts General Hospital. NR 32 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JAN-FEB PY 2009 VL 23 IS 1 BP 108 EP 115 DI 10.1016/j.avsg.2008.05.003 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 392UX UT WOS:000262328800017 PM 18640815 ER PT S AU Yarmush, ML King, KR AF Yarmush, Martin L. King, Kevin R. TI Living-Cell Microarrays SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING SE ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review; Book Chapter DE high-throughput screening; cell microarrays; reverse transfection; microfabrication; microfluidics; single-cell analysis ID GENOME-WIDE RNAI; THROUGHPUT SCREENING ASSAYS; GREEN FLUORESCENT PROTEIN; ROBUST MICROSCALE ASSAYS; GENE-EXPRESSION; REVERSE TRANSFECTION; IN-VITRO; TISSUE MORPHOGENESIS; NONPARENCHYMAL CELLS; MANAGING EVAPORATION AB Living cells are remarkably complex. To unravel this complexity, living-cell assays have been developed that allow delivery of experimental stimuli and measurement of the resulting cellular responses. High-throughput adaptations of these assays, known as living-cell microarrays, which are based on microtiter plates, high-density spotting, microfabrication, and microfluidics technologies, are being developed for two general applications: (it) to screen large-scale chemical and genomic libraries and (b) to systematically investigate the local cellular microenvironment. These emerging experimental platforms offer exciting opportunities to rapidly identify genetic determinants of disease, to discover modulators of cellular function, and to probe the complex and dynamic relationships between cells and their local environment. C1 [Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Sci, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Sci, Boston, MA 02114 USA. EM ireis@sbi.org FU NIH [R01 AI063795, P41 EB002503]; Shriners Burns Hospital [8495] FX The authors' work in this area is supported by funds from NIH grants; R01 AI063795 and P41 EB002503 and by a postdoctoral fellowship, #8495, from the Shriners Burns Hospital. NR 116 TC 73 Z9 76 U1 2 U2 40 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 BN 978-0-8243-3511-3 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2009 VL 11 BP 235 EP 257 DI 10.1146/annurev.bioeng.10.061807.160502 PG 23 WC Engineering, Biomedical SC Engineering GA 539NM UT WOS:000273261600010 PM 19413510 ER PT S AU Nohturfft, A Zhang, SC AF Nohturfft, Axel Zhang, Shao Chong TI Coordination of Lipid Metabolism in Membrane Biogenesis SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE cholesterol; ergosterol; phospholipid; transcriptional control; feedback regulation; cross-regulation ID STEROL REGULATORY ELEMENT; CLEAVAGE-ACTIVATING PROTEIN; YEAST SACCHAROMYCES-CEREVISIAE; HMG-COA REDUCTASE; DENSITY-LIPOPROTEIN RECEPTOR; FATTY-ACID SYNTHESIS; LIVER-X-RECEPTOR; INFANTILE NEUROAXONAL DYSTROPHY; PHOSPHATIDATE PHOSPHATASE-ACTIVITY; ENDOPLASMIC-RETICULUM CHOLESTEROL AB Biliyer synthesis during membrane biogenesis involves the concerted assembly of multiple lipid species, requiring coordination of the level of lipid synthesis, uptake, turnover, and subcellular distribution. In this review, we discuss some of the salient conclusions regarding the coordination of lipid synthesis that have emerged from work in mammalian and yeast cells. The principal instruments of global control are a small number of transcription factors that target a wide range of genes encoding enzymes that operate in a given metabolic pathway. Critical in mammalian cells are sterol regulatory element binding proteins (SREBPs) that stimulate expression of genes for the uptake and synthesis of cholesterol and fatty acids. From work with Saccharomyces cerevisiae, much has been learned about glycerophospholipid and ergosterol regulation through Ino2p/Ino4p and Upc2p transcription factors, respectively. Lipid supply is fine-tuned through a multitude of negative feedback circuits initiated by both end products and intermediates of lipid synthesis pathways. Moreover, there is evidence that the diversity of membrane lipids is maintained through cross-regulatory effects, whereby classes of lipids activate the activity of enzymes operating in another metabolic branch. C1 [Nohturfft, Axel] St Georges Univ London, Mol & Metab Signalling Ctr, Div Basic Med Sci, London SW17 0RE, England. [Zhang, Shao Chong] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA. RP Nohturfft, A (reprint author), St Georges Univ London, Mol & Metab Signalling Ctr, Div Basic Med Sci, London SW17 0RE, England. EM a.nohturfft@sgul.ac.uk RI Wilkinson, Stuart/C-2802-2013 FU National Institutes of Health [DK59934]; Ara Parseghian Medical Research Foundation; Searle scholarship FX The authors are thankful to Tim Levine (University College London) for critical comments on a draft version of this manuscript. Our work on lipid metabolism was supported by funding from the National Institutes of Health (DK59934), the Ara Parseghian Medical Research Foundation, and a Searle scholarship to A.N. NR 245 TC 66 Z9 68 U1 1 U2 23 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 BN 978-0-8243-3125-2 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2009 VL 25 BP 539 EP 566 DI 10.1146/annurev.cellbio.24.110707.175344 PG 28 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 521GF UT WOS:000271907700022 PM 19575637 ER PT S AU Karsenty, G Kronenberg, HM Settembre, C AF Karsenty, Gerard Kronenberg, Henry M. Settembre, Carmine TI Genetic Control of Bone Formation SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE endochondral ossification; chondrocytes; osteoblasts; transcription factors; signaling molecules ID GROWTH-FACTOR RECEPTOR-3; HYPERTROPHIC CHONDROCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR OSF2/CBFA1; SYMPATHETIC-NERVOUS-SYSTEM; SAETHRE-CHOTZEN SYNDROME; HORMONE-RELATED PEPTIDE; AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; INDIAN-HEDGEHOG; OSTEOBLAST DIFFERENTIATION AB In the past few years, our molecular understanding of bone formation has continued to increase. This review aims to present a comprehensive view of the current state of knowledge in the field. Thus, it will cover our current knowledge of chondrogenesis and osteoblastogenesis. It will also cover the most salient aspects of osteoblast function. C1 [Karsenty, Gerard; Settembre, Carmine] Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA. [Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Karsenty, G (reprint author), Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA. EM gk2172@columbia.edu OI SETTEMBRE, Carmine/0000-0002-5829-8589 FU NIH [2 R01 DK067936, 5 RO1 DE01 1290] FX This work was supported by NIH grants 2 R01 DK067936 and 5 RO1 DE01 1290. NR 117 TC 254 Z9 269 U1 6 U2 32 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 BN 978-0-8243-3125-2 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2009 VL 25 BP 629 EP 648 DI 10.1146/annurev.cellbio.042308.113308 PG 20 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 521GF UT WOS:000271907700025 PM 19575648 ER PT S AU Moldovan, GL D'Andrea, AD AF Moldovan, George-Lucian D'Andrea, Alan D. TI How the Fanconi Anemia Pathway Guards the Genome SO ANNUAL REVIEW OF GENETICS SE Annual Review of Genetics LA English DT Review; Book Chapter DE DNA repair; interstrand crosslink; cancer; homologous recombination; translesion synthesis; protein ubiquitination ID CROSS-LINK REPAIR; DNA-DAMAGE-RESPONSE; NUCLEOTIDE EXCISION-REPAIR; STALLED REPLICATION FORKS; CORE COMPLEX; HOMOLOGOUS RECOMBINATION; BREAST-CANCER; S-PHASE; TARGETED DISRUPTION; PROTEIN COMPLEX AB Fanconi Anemia (FA) is an inherited genomic instability disorder, caused by mutations in genes regulating replication-dependent removal of interstrand DTNA crosslinks. The Fanconi Anemia pathway is thought to coordinate a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in response to genotoxic insults. To this end, the Fanconi Anemia pathway employs a unique nuclear protein complex that ubiquitinates FANCD2 and FANCI, leading to formation of DNA repair structures. Lack of obvious enzymatic activities among most FA members has made it challenging to unravel its precise modus operandi. Here we review the current understanding of how the Fanconi Anemia pathway components participate in DNA repair and discuss the mechanisms that regulate this pathway to ensure timely, efficient, and correct restoration of chromosomal integrity. C1 [Moldovan, George-Lucian; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Moldovan, GL (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu OI George-Lucian, Moldovan/0000-0003-3825-149X FU NIH [RO1DK43889, RO1HL52725, PO1DK50654, U19A1067751, 5PO1CA092584]; International Human Frontiers Science Program Organization FX We would like to thank Johannes Walter, Patrizia Vinciguerra, Younghoon Kee, and Mahesh Madhavan for helpful discussions and comments, and Lisa Moreau for providing Figure 1a. We ire grateful to our colleagues for sharing Unpublished results. The work was supported by NIH grants RO1DK43889, RO1HL52725, PO1DK50654, U19A1067751, and 5PO1CA092584. GLM is supported by a postdoctoral fellowship from the International Human Frontiers Science Program Organization. NR 171 TC 305 Z9 315 U1 4 U2 33 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 BN 978-0-8243-1243-5 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2009 VL 43 BP 223 EP 249 DI 10.1146/annurev-genet-102108-134222 PG 27 WC Genetics & Heredity SC Genetics & Heredity GA 543LW UT WOS:000273580300010 PM 19686080 ER PT J AU Dougan, M Dranoff, G AF Dougan, Michael Dranoff, Glenn TI Immune Therapy for Cancer SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE monoclonal (antibody); inflammation; vaccine; adjuvants; immunotherapy ID REGULATORY T-CELLS; COLONY-STIMULATING FACTOR; GROWTH-FACTOR RECEPTOR; METASTATIC BREAST-CANCER; BACILLUS-CALMETTE-GUERIN; TUMOR-NECROSIS-FACTOR; PHASE-III TRIAL; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RECOMBINANT INTERLEUKIN-2 THERAPY; HELICOBACTER-PYLORI ERADICATION AB Over the past decade, immune therapy has become a standard treatment for a variety of cancers. Monoclonal antibodies, immune adjuvants, and vaccines against oncogenic viruses are now well-established cancer therapies. Immune modulation is a principal element of supportive care for many high-dose chemotherapy regimens. In addition, immune activation is now appreciated as central to the therapeutic mechanism of bone marrow transplantation for hematologic malignancies. Advances in our understanding of the molecular interactions between tumors and the immune system have led to many novel investigational therapies and continue to inform efforts for devising more potent therapeutics. Novel approaches to immune-based cancer treatment strive to augment antitumor immune responses by expanding tumor-reactive T cells, providing exogenous immune-activating stimuli, and antagonizing regulatory pathways that induce immune tolerance. The future of immune therapy for cancer is likely to combine many of these approaches to generate more effective treatments. C1 [Dougan, Michael] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dougan, M (reprint author), Brigham & Womens Hosp, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu NR 238 TC 306 Z9 323 U1 14 U2 97 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 EI 1545-3278 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2009 VL 27 BP 83 EP 117 DI 10.1146/annurev.immunol.021908.132544 PG 35 WC Immunology SC Immunology GA 471PW UT WOS:000268071600004 PM 19007331 ER PT S AU Mathis, D Benoist, C AF Mathis, Diane Benoist, Christophe TI Aire SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE T cell tolerance; autoimmunity; thymus; transcription factor ID CANDIDIASIS-ECTODERMAL DYSTROPHY; THYMIC EPITHELIAL-CELLS; AUTOIMMUNE REGULATOR AIRE; POLYGLANDULAR SYNDROME TYPE-1; PROMISCUOUS GENE-EXPRESSION; ORGAN-SPECIFIC AUTOIMMUNITY; ANTIGEN-PRESENTING CELL; DISEASE TYPE-I; T-CELLS; CENTRAL TOLERANCE AB Mutations in the transcriptional regulator, Aire, cause APECED, a polyglandular autoimmune disease with monogenic transmission. Animal models of APECED have revealed that Aire plays an important role in T cell tolerance induction in the thymus, mainly by promoting ectopic expression of a large repertoire of transcripts encoding proteins normally restricted to differentiated organs residing in the periphery. The absence of Aire results in impaired clonal deletion of self-reactive thymocytes, which escape into the periphery and attack a variety of organs. In addition, Aire is a proapoptotic factor, expressed at the final maturation stage of thymic medullary epithelial cells, a function that may promote cross-presentation of the antigens encoded by Aire-induced transcripts in these cells. Transcriptional regulation by Aire is unusual in being very broad, context-dependent, probabilistic, and noisy. Structure/function analyses and identification of its interaction partners suggest that Aire may impact transcription at several levels, including nucleosome displacement during elongation and transcript splicing or other aspects of maturation. C1 [Mathis, Diane] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. EM cbdm@joslin.harvard.edu FU NIH [RO1 DK60027]; William T Young Chair in Diabetes Research FX The CBDM labs work on Aire has been supported by NIH RO1 DK60027 and by the William T Young Chair in Diabetes Research. For their important contributions, we thank H. Yoshida, J. Villasenor, E. Venanzi, J. Lopes, A. Koh, J. Johnnidis, W Jiang, E. Husebye, M. Guerau-de-Arellano, D. Gray, M. Giraud, I. Gavanescu, M.S. Anderson, and J. Abramson. NR 151 TC 323 Z9 331 U1 0 U2 33 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3027-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2009 VL 27 BP 287 EP 312 DI 10.1146/annurev.immunol.25.022106.141532 PG 26 WC Immunology SC Immunology GA 471PW UT WOS:000268071600011 PM 19302042 ER PT J AU Kuter, DJ AF Kuter, David J. TI Thrombopoietin and Thrombopoietin Mimetics in the Treatment of Thrombocytopenia SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE romiplostim; eltrombopag; immune thrombocytopenic purpura (ITP); platelets ID HUMAN MEGAKARYOCYTE GROWTH; RECOMBINANT HUMAN THROMBOPOIETIN; TPO RECEPTOR AGONIST; FACTOR PEG-RHUMGDF; C-MPL; PLATELET PRODUCTION; CYTOKINE RECEPTOR; HEALTHY-VOLUNTEERS; ANTIBODY FRAGMENT; CONTROLLED-TRIAL AB Although the thrombopoietin receptor was discovered in 1991 and thrombopoietin (TPO) was purified in 1994, the development of a clinically useful TPO was hampered by the appearance of neutralizing antibodies to some forms of recombinant TPO. However, in 2008 two new drugs that mimic the effect of TPO became available to treat thrombocytopenia. Romiplostim is a TPO peptide mimetic given by Subcutaneous injection that activates the TPO receptor by binding to the distal hematopoietic receptor domain just like TPO. Eltrombopag is a TPO nonpeptide mimetic administered orally that activates the TPO receptor by binding to the transmembrane domain. Both increase the platelet count in healthy humans as well as in > 80% of patients with immune thrombocytopenic purpura (ITP). Although initially restricted to the second-line treatment of ITP, both agents could help treat many thrombocytopenic disorders. Both agents are well tolerated, with mild headache being the most common complaint. Potential long-term complications include thrombosis, increased bone marrow reticulin, rebound worsening of thrombocytopenia upon discontinuation, and increased blast formation. Ongoing studies should establish the incidence of these complications and determine the efficacy of these new agents in a variety of other thrombocytopenic conditions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM kuter.david@MGH.harvard.edu FU National Institutes of Health [HL72299, HL82889] FX This work was supported in part by the National Institutes of Health (grants HL72299 and HL82889). NR 60 TC 83 Z9 86 U1 0 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2009 VL 60 BP 193 EP 206 DI 10.1146/annurev.med.60.042307.181154 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 471PS UT WOS:000268071100015 PM 19642221 ER PT S AU Costigan, M Scholz, J Woolf, CJ AF Costigan, Michael Scholz, Joachim Woolf, Clifford J. TI Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage SO ANNUAL REVIEW OF NEUROSCIENCE SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE neural plasticity; synaptic facilitation; disinhibition; neuroimmune interaction; pain phenotype ID SPINAL DORSAL-HORN; CHRONIC CONSTRICTION INJURY; PRIMARY SENSORY NEURONS; GATED SODIUM-CHANNELS; ROOT GANGLION NEURONS; SUBSTANTIA-GELATINOSA NEURONS; PERIPHERAL-NERVE; CENTRAL SENSITIZATION; SCIATIC-NERVE; UP-REGULATION AB Neuropathic pain is triggered by lesions to the somatosensory, nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely Suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk. C1 [Costigan, Michael] Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Costigan, M (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. EM mcostigan@partners.org; scholz.joachim@mgh.harvard.edu; cwoolf@partners.org FU NINDS NIH HHS [R01 NS050408, R01 NS050408-02] NR 192 TC 577 Z9 595 U1 11 U2 107 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X BN 978-0-8243-2432-2 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2009 VL 32 BP 1 EP 32 DI 10.1146/annurev.neuro.051508.135531 PG 32 WC Neurosciences SC Neurosciences & Neurology GA 477FM UT WOS:000268504100001 PM 19400724 ER PT S AU Ibrahim, N Haluska, FG AF Ibrahim, Nageatte Haluska, Frank G. TI Molecular Pathogenesis of Cutaneous Melanocytic Neoplasms SO ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE melanoma genetics; familial melanoma; BRAF; MAPK pathway; CDKN2A; apoptosis ID CELL-CYCLE ARREST; C-KIT EXPRESSION; FACTOR RECEPTOR PROTOONCOGENE; TRANSCRIPTION FACTOR GENE; KINASE-4 INHIBITOR GENE; MELANOMA-PRONE FAMILIES; PHASE-II TRIAL; MALIGNANT-MELANOMA; METASTATIC MELANOMA; GERMLINE MUTATIONS AB Melanoma is the deadliest form of skin cancer without an effective treatment. An understanding of the genetic basis of melanoma has recently shed light on some of the mechanisms of melanomagenesis. This review explores the major genes involved in familial and sporadic Cutaneous melanoma with an emphasis on CDKN2A, CDK4, MC1R, and MAPK pathway targets (e.g., RAS and BRAF), apoptosis regulators (e.g., BCL-2, AKT, and APAF-1),and the tumor-suppressor genes TP53 and PTEN. New directions for therapeutics based on our current knowledge of the genes implicated in melanoma are also discussed. C1 [Ibrahim, Nageatte] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Haluska, Frank G.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. RP Ibrahim, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM nibrahim@partners.org NR 187 TC 68 Z9 69 U1 1 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1553-4006 BN 978-0-8243-4304-0 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech. Dis. PY 2009 VL 4 BP 551 EP 579 DI 10.1146/annurev.pathol.3.121806.151541 PG 29 WC Pathology SC Pathology GA 471PX UT WOS:000268071700022 PM 19400696 ER PT S AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Neuroendocrine Control of the Gut During Stress: Corticotropin-Releasing Factor Signaling Pathways in the Spotlight SO ANNUAL REVIEW OF PHYSIOLOGY SE Annual Review of Physiology LA English DT Review; Book Chapter DE motility; CRF antagonists; colon; stomach; urocortin ID IRRITABLE-BOWEL-SYNDROME; CENTRAL-NERVOUS-SYSTEM; COLONIC MOTOR FUNCTION; DORSAL VAGAL COMPLEX; FACTOR-RECEPTOR SUBTYPE-1; HORMONE TYPE-1 RECEPTOR; WATER-AVOIDANCE STRESS; FACTOR CRF ANTAGONIST; BINDING-PROTEIN; RAT-BRAIN AB Stress affects the gastrointestinal tract as part of the visceral response. Various stressors induce similar profiles Of gut motor function alterations, including inhibition of gastric emptying, stimulation of colonic propulsive motility, and hypersensitivity to colorectal distension. In recent years, substantial progress has been made in our understanding of the underlying mechanisms of stress's impact on gut function. Activation of corticotropin-releasing factor (CRF) signaling pathways mediates both the inhibition of upper gastrointestinal (GI) and the stimulation of lower GI motor function through interaction with different CRF receptor subtypes. Here, we review how various stressors affect the gut, with special emphasis on the central and peripheral CRF signaling systems. C1 [Stengel, Andreas] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Neurobiol Stress, Cure Digest Dis Res Ctr, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Stengel, A (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIAMS NIH HHS [P50 AR 049550]; NIDDK NIH HHS [DK-41301, P30 DK041301, R01 DK033061, R01 DK057238, R01 DK057238-08, R01 DK-33061, DK57238] NR 174 TC 51 Z9 59 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 BN 978-0-8243-0371-6 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2009 VL 71 BP 219 EP 239 DI 10.1146/annurev.physiol.010908.163221 PG 21 WC Physiology SC Physiology GA 423II UT WOS:000264489600011 PM 18928406 ER PT S AU Bennett, GG Glasgow, RE AF Bennett, Gary G. Glasgow, Russell E. TI The Delivery of Public Health Interventions via the Internet: Actualizing Their Potential SO ANNUAL REVIEW OF PUBLIC HEALTH SE Annual Review of Public Health LA English DT Review; Book Chapter DE eHealth; World Wide Web; treatment; interactive; interactive health communication; health behavior ID RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY INTERVENTION; SMOKING-CESSATION PROGRAM; WEB-BASED INTERVENTION; WEIGHT-LOSS PROGRAM; COGNITIVE-BEHAVIORAL THERAPY; GLUCOSE MONITORING-SYSTEM; CONTROLLED CLINICAL-TRIAL; CONGESTIVE-HEART-FAILURE; SHORT-MESSAGE SERVICE AB The Internet increasingly serves as a platform for the delivery of public health interventions. The efficacy of Internet interventions has been demonstrated across a wide range of conditions. Much more work remains, however, to enhance the potential for broad population dissemination of Internet interventions. In this article, we examine the effectiveness of Internet interventions, with particular attention to their dissemination potential. We discuss several considerations (characterizing reach rates, minimizing attrition, promoting Web site utilization, use of tailored messaging and social networking) that may improve the implementation of Internet interventions and their associated outcomes. We review factors that may influence the adoption of Internet interventions in a range of potential dissemination settings. Finally, we present several recommendations for future research that highlight the potential importance of better understanding intervention reach, developing consensus regarding Web site usage metrics, and more broadly integrating Web 2.0 functionality. C1 [Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Glasgow, Russell E.] Kaiser Permanente Colorado, Clin Res Unit, Denver, CO 80237 USA. RP Bennett, GG (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM gbennett@hsph.harvard.edu NR 162 TC 296 Z9 297 U1 8 U2 88 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 BN 978-0-8243-2730-9 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2009 VL 30 BP 273 EP 292 DI 10.1146/annurev.publhealth.031308.100235 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 471PZ UT WOS:000268071900016 PM 19296777 ER PT J AU Finegold, SM Molitoris, D Vaisanen, ML AF Finegold, S. M. Molitoris, D. Vaisanen, M.-L. TI Study of the In Vitro Activities of Rifaximin and Comparator Agents against 536 Anaerobic Intestinal Bacteria from the Perspective of Potential Utility in Pathology Involving Bowel Flora SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID VOLUNTEERS AB Rifaximin, ampicillin-sulbactam, neomycin, nitazoxanide, teicoplanin, and vancomycin were tested against 536 strains of anaerobic bacteria. The overall MIC of rifaximin at which 50% of strains were inhibited was 0.25 mu g/ml. Ninety percent of the strains tested were inhibited by 256 mu g/ml of rifaximin or less, an activity equivalent to those of teicoplanin and vancomycin but less than those of nitazoxanide and ampicillin-sulbactam. C1 [Finegold, S. M.] VA Greater Angeles Healthcare Syst, Med Serv, Los Angeles, CA USA. [Finegold, S. M.; Molitoris, D.; Vaisanen, M.-L.] VA Greater Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Finegold, S. M.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Finegold, S. M.] Univ Calif Los Angeles, Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA. RP Finegold, SM (reprint author), Greater Los Angeles VAMC, 11301 Wilshire Blvd,Bldg 304,Rm E3-237, Los Angeles, CA 90073 USA. EM sidfinegol@aol.com FU Salix Pharmaceuticals, Inc., Morrisville, NC FX This study was supported in part by a grant from Salix Pharmaceuticals, Inc., Morrisville, NC. NR 12 TC 15 Z9 15 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 JAN PY 2009 VL 53 IS 1 BP 281 EP 286 DI 10.1128/AAC.00441-08 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 387JW UT WOS:000261949500040 PM 18955526 ER PT J AU Thompson, GR Wiederhold, NP Fothergill, AW Vallor, AC Wickes, BL Patterson, TF AF Thompson, George R., III Wiederhold, Nathan P. Fothergill, Annette W. Vallor, Ana C. Wickes, Brian L. Patterson, Thomas F. TI Antifungal Susceptibilities among Different Serotypes of Cryptococcus gattii and Cryptococcus neoformans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO SUSCEPTIBILITIES; 2 VARIETIES; EPIDEMIOLOGY; INFECTION; DRUGS; HOST AB We measured antifungal activity against 128 cryptococcal isolates (86 of C. neoformans and 42 of C. gattii) to determine if differences in serotype susceptibility exist. Contrary to previous results, we found no serotype susceptibility differences. Isavuconazole, posaconazole, and voriconazole demonstrated excellent potency against each isolate and serotype, including isolates with reduced fluconazole susceptibilities. C1 [Thompson, George R., III; Wiederhold, Nathan P.; Vallor, Ana C.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, Div Infect Dis, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Fothergill, Annette W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. [Wickes, Brian L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol, San Antonio, TX 78229 USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Thompson, George R., III; Wiederhold, Nathan P.; Vallor, Ana C.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Thompson, GR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM thompsong2@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU NIH [NOI-A1-25475]; Pfizer; ScheringPlough; Merck; Nektar Therapeutics FX G. R. T., A. W. F, A. C. V., and B. L. W. report no conflicts of interest. N. P. W. has received research support from Pfizer and ScheringPlough. T. F. P. has received research support from Merck, Pfizer, ScheringPlough, and Nektar Therapeutics and has served on the speaker's bureau for Merck and Pfizer and as a consultant for Basilea, Merck, Nektar, Pfizer, and Toyama. NR 20 TC 70 Z9 71 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 JAN PY 2009 VL 53 IS 1 BP 309 EP 311 DI 10.1128/AAC.01216-08 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 387JW UT WOS:000261949500047 PM 18955539 ER PT B AU Lopez-Ribot, JL Patterson, TF AF Lopez-Ribot, Jose L. Patterson, Thomas F. BE Mayers, DL TI Fungal Drug Resistance: Azoles SO ANTIMICROBIAL DRUG RESISTANCE, VOL 1: MECHANISMS OF DRUG RESISTANCE SE Infectious Disease LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; CANDIDA-ALBICANS STRAINS; YEAST MULTIDRUG-RESISTANCE; AMINO-ACID SUBSTITUTIONS; ABC TRANSPORTERS CDR1; MESSENGER-RNA LEVELS; ANTIFUNGAL AGENTS; FLUCONAZOLE RESISTANCE; OROPHARYNGEAL CANDIDIASIS; INFECTED PATIENTS C1 [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Lopez-Ribot, Jose L.] Univ Texas San Antonio, Dept Biol, San Antonio, TX USA. [Lopez-Ribot, Jose L.] Univ Texas San Antonio, S Texas Ctr Emerging Infect Dis, San Antonio, TX USA. RP Patterson, TF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio, TX 78229 USA. EM patterson@uthscsa.edu NR 61 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-592-7 J9 INFECT DIS PY 2009 BP 307 EP 312 DI 10.1007/978-1-59745-180-2_26 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA BKN91 UT WOS:000268730400026 ER PT J AU Gowen, BB Fairman, J Dow, S Troyer, R Wong, MH Jung, KH Melby, PC Morrey, JD AF Gowen, Brian B. Fairman, Jeff Dow, Steven Troyer, Ryan Wong, Min-Hui Jung, Kie-Hoon Melby, Peter C. Morrey, John D. TI Prophylaxis with cationic liposome-DNA complexes protects hamsters from phleboviral disease: Importance of liposomal delivery and CpG motifs SO ANTIVIRAL RESEARCH LA English DT Article DE Liposomes; Antiviral; CpG; Rift Valley fever; Punta Toro virus; Phlebovirus ID RIFT-VALLEY FEVER; PUNTA-TORO-VIRUS; INNATE IMMUNE-RESPONSE; BACTERIAL-DNA; TLR9-INDEPENDENT PATHWAYS; HEMORRHAGIC-FEVER; DENDRITIC CELLS; RHESUS-MONKEYS; INFECTION; PATHOGENESIS AB Cationic liposome-DNA complexes (CLDC) are cationic/neutral lipid carriers complexed with plasmid DNA that when administered systemically results in a robust T(H)1 cytokine response. CLDC have been shown to be effective in prophylaxis and therapeutic treatment of animal models of viral disease. To determine the contribution of liposomal delivery and CpG content of the plasmid DNA to the efficacy of CLDC; plasmid, CpG-free plasmid DNA, or CpG-containing oligodeoxynucleotides (ODN) with and without liposomes, as well as poly(I:C(12)U), were evaluated for their ability to elicit protection against lethal Punta Toro virus (PTV, Bunyaviridae, phlebovirus) challenge in hamsters. CLDC-containing plasmid significantly improved survival, decreased systemic and liver viral loads, and reduced liver damage due to progression of viral infection. Mouse-reactive ODNs complexed with liposomes failed to protect hamsters, whereas ODNs known to cross-react with human and mouse (CpG 2006) or non-liposomal poly(I:C(12)U) showed survival benefit but did not limit liver injury. Liposomes complexed with a non-CpG motif-containing plasmid reduced liver viral load and tissue damage, but did not protect hamsters from death. To evaluate the mechanisms of the enhanced activity of CLDC, microarray experiments examined differences in the gene expression profile. The results suggest a broad T(H)1 response elicited by liposomal delivery of a diverse sequence containing CpG and non-CpG elements may be a more effective antiviral treatment than other nucleic acid based immunotherapeutics. (C) 2008 Elsevier B.V. All rights reserved. C1 [Gowen, Brian B.; Wong, Min-Hui; Jung, Kie-Hoon; Morrey, John D.] Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA. [Gowen, Brian B.; Wong, Min-Hui; Jung, Kie-Hoon; Morrey, John D.] Utah State Univ, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA. [Fairman, Jeff] Juvaris BioTherapeut, Buringame, CA USA. [Dow, Steven; Troyer, Ryan] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Melby, Peter C.] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Gowen, BB (reprint author), Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA. EM bgowen@cc.usu.edu FU Virology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health [N01-AI-15435]; National Institute of Allergy and Infectious Diseases, National Institutes of Health [1R43AI060146-01A2] FX This work was supported by contract grant N01-AI-15435 from the Virology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health and grant 1R43AI060146-01A2 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health NR 43 TC 16 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 2009 VL 81 IS 1 BP 37 EP 46 DI 10.1016/j.antiviral.2008.09.001 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 396KF UT WOS:000262589900005 PM 18840471 ER PT J AU Orrell, C Walensky, RP Losina, E Pitt, J Freedberg, KA Wood, R AF Orrell, Catherine Walensky, Rochelle P. Losina, Elena Pitt, Jennifer Freedberg, Kenneth A. Wood, Robin TI HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme SO ANTIVIRAL THERAPY LA English DT Article ID RESOURCE-LIMITED SETTINGS; FIXED-DOSE COMBINATION; SOUTH-AFRICA; SUBTYPE-C; DRUG-RESISTANCE; HIV-1-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE; INITIAL REGIMEN; PREVALENCE; K65R AB Background: This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa. Methods: This was an observational cohort. Genotypic resistance testing was performed on treatment-naive individuals and those failing first-line ART (confirmed HIV-1 RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002-2007). Resistance profiles and mutations relative to timing of known virological failure were examined. Results: In total, 230 patients (120 treatment-naive and I 10 with virological failure) were included: 98% had clade C virus. Among treatment-naive patients, prevalence of primary resistance was 2.5% (95% confidence interval 0.0-5.3). Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A. Among treatment-experienced patients, 95 (86%) individuals had therapy-limiting NNRTI mutations, including K103N (55%), V106M (31%) and Y181C (9%). The M184V mutation was the most common mutation, found in 86 (78%) patients. In total, 10 (9%) patients had the K65R mutation. More individuals tended to develop thymidine analogue mutations when sampling occurred after 6 months of detected therapy failure (10/31 [32%] individuals) compared with those who had genotyping before 6 months (115/79 [19%] patients; P=0.246). Conclusions: Prevalence of primary resistance in a sample of ART-naive clade C HIV-1-infected individuals in South Africa was low during the study period. Patients failing first-line ART most often developed resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, the two drug classes used in first-line therapy. Viral load monitoring in this setting is crucial and individual genotypes in those failing first-line therapy should be considered. C1 [Orrell, Catherine; Pitt, Jennifer; Wood, Robin] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Fdn, ZA-7925 Cape Town, South Africa. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med & Infect Dis, Boston, MA USA. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Harvard Ctr AIDS Res, Div Gen Med & Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Losina, Elena] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA USA. RP Orrell, C (reprint author), Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Fdn, ZA-7925 Cape Town, South Africa. EM catherine.orrell@hiv-research.org.za RI Wood, Robin/G-8509-2011; OI Walensky, Rochelle P./0000-0002-8795-379X; Orrell, Catherine/0000-0003-1134-7475 FU National Institute of Allergy and Infectious Diseases [R01 A1058736, K24 A1062476, P30 A10603S4]; Doris Duke Charltable Foundation Clinical Scientist Development Award FX This work was supported by the National Institute of Allergy and Infectious Diseases (R01 A1058736, K24 A1062476, P30 A10603S4) and the Doris Duke Charltable Foundation Clinical Scientist Development Award. NR 31 TC 68 Z9 69 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 BP 523 EP 531 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900006 PM 19578237 ER PT J AU Chaix, ML Messou, E Gabillard, D Minga, A Losina, E N'Dri-Yoman, T Freedberg, K Rouzioux, C Danel, C Anglaret, X AF Chaix, M. L. Messou, E. Gabillard, D. Minga, A. Losina, E. N'Dri-Yoman, T. Freedberg, K. Rouzioux, C. Danel, C. Anglaret, X. TI Association between medication possession ratio and virological M6 and M12 outcomes in HIV-1-infected adults on antiretroviral treatment in Abidjan, Cote d'Ivoire SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Chaix, M. L.; Rouzioux, C.] Univ Paris 05, CHU Necker, EA 3620, Paris, France. [Messou, E.; Minga, A.; N'Dri-Yoman, T.; Danel, C.] Ctr Rech Epidemiol & Biostat, INSERM, U897, Bordeaux, France. [Gabillard, D.; Anglaret, X.] Programme PACCI, Abidjan, Cote Ivoire. [Losina, E.; Freedberg, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Anglaret, Xavier/F-7333-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 164 BP A187 EP A187 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900181 ER PT J AU Lo, J You, SM Liebau, J Wei, J Hemphill, L Lee, H Grinspoon, S AF Lo, J. You, S. M. Liebau, J. Wei, J. Hemphill, L. Lee, H. Grinspoon, S. TI Effects of treatment and discontinuation of low dose physiologic growth hormone in HIV patients with abdominal fat accumulation: a randomized, placebo-controlled 36-month crossover trial SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 11th International Workshop on AdverseDrug Reactions and Co-Morbidities in HIV CY OCT 26-28, 2009 CL Philadelphia, PA C1 [Lo, J.; You, S. M.; Liebau, J.; Wei, J.; Grinspoon, S.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Lo, J.; You, S. M.; Liebau, J.; Wei, J.; Grinspoon, S.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Hemphill, L.] Boston Heart Fdn, Boston, MA USA. [Lee, H.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 7 BP A3 EP A4 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 523GH UT WOS:000272060000019 ER PT J AU Palmer, S King, M Wiegand, A Miura, T Block, B Pereyra, F Maldarelli, F Dahl, V Mellors, J Walker, B Coffin, JM AF Palmer, S. King, M. Wiegand, A. Miura, T. Block, B. Pereyra, F. Maldarelli, F. Dahl, V. Mellors, J. Walker, B. Coffin, J. M. TI Longitudinal dynamics of persistent viremia in elite controller patients versus patients on suppressive therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Palmer, S.; Dahl, V.] Karolinska Inst, Swedish Inst Infect Dis Control, S-10401 Stockholm, Sweden. [Palmer, S.; Wiegand, A.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [King, M.] Abbott Labs, Abbott Pk, IL 60064 USA. [Miura, T.; Block, B.; Pereyra, F.; Walker, B.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Coffin, J. M.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 4 BP A6 EP A6 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900021 ER PT J AU Turner, RR McColl, SL Falutz, J Testa, MA Potvin, D Mamputu, JC Michaud, SE Marsolais, C Soulban, G Assaad, H Su, M Grinspoon, S AF Turner, R. R. McColl, S. L. Falutz, J. Testa, M. A. Potvin, D. Mamputu, J-C Michaud, S-E Marsolais, C. Soulban, G. Assaad, H. Su, M. Grinspoon, S. TI The impact and clinical relevance of tesamorelin (TH9507), a growth hormone-releasing factor analogue, on belly and weight image and health-related quality of life (HRQOL) in HIV-infected patients with excess abdominal fat: a combined analysis of two Phase III studies SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 11th International Workshop on AdverseDrug Reactions and Co-Morbidities in HIV CY OCT 26-28, 2009 CL Philadelphia, PA C1 [Turner, R. R.; Su, M.] Phase V Technol Inc, Wellesley, MA USA. [McColl, S. L.; Potvin, D.; Mamputu, J-C; Michaud, S-E; Marsolais, C.; Soulban, G.; Assaad, H.] Theratechnologies Inc, Montreal, PQ, Canada. [Falutz, J.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Falutz, J.] Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. [Testa, M. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Grinspoon, S.] Harvard Univ, Sch Med, Boston, MA USA. [Grinspoon, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 7 BP A4 EP A4 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 523GH UT WOS:000272060000020 ER PT J AU Salters-Pedneault, K Vine, V Mills, MA Park, C Litz, BT AF Salters-Pedneault, Kristalyn Vine, Vera Mills, Mary Alice Park, Crystal Litz, Brett T. TI The experience of intrusions scale: A preliminary examination SO ANXIETY STRESS AND COPING LA English DT Article DE anxiety; intrusions; trauma; cognitive processing; cognition; information processing ID THOUGHT SUPPRESSION; PSYCHOMETRIC PROPERTIES; INDIVIDUAL-DIFFERENCES; STRESSFUL FILM; MEMORIES; IMAGERY; DEPRESSION; CHECKLIST; EMOTION AB Intrusive thoughts (i.e., unwelcome, distressing, involuntary thoughts) are prevalent in a variety of clinical conditions and are increasingly a focus of translational research. The goal of this study was to develop and preliminarily examine a brief self-report measure designed to assess clinically relevant aspects of the experience of intrusive thoughts related to a particular target. The Experience of Intrusions Scale (EIS) is a five-item measure that assesses the frequency, unpredictability, and unwantedness of intrusive thoughts, as well as the interference and distress caused by the intrusions, each on a five-point Likert-type scale. Five times over a four-] period, female undergraduates (N=160) completed the EIS in response to intrusive thoughts regarding a film clip depicting a sexual assault. On the first and last days, participants completed the EIS five minutes after watching the clip. In between film clip viewings, participants completed the EIS once per day. The EIS demonstrated good internal consistency, good to excellent test-retest reliability using both immediate post-stimulus and 24-hour time intervals, and convergent validity with two existing measures of intrusive phenomena: the White Bear Suppression Inventory (Wegner Zanakos, 1994) and the Post-traumatic Stress Disorder Checklist-Civilian Version (Weathers, Litz, Herman, Huska, Keane, 1993). C1 [Salters-Pedneault, Kristalyn; Vine, Vera; Litz, Brett T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Mills, Mary Alice; Park, Crystal] Univ Connecticut, Storrs, CT USA. RP Salters-Pedneault, K (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. EM kristalyn.salters@va.gov NR 40 TC 7 Z9 7 U1 3 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2009 VL 22 IS 1 BP 27 EP 37 AR PII 904507571 DI 10.1080/10615800802403823 PG 11 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 385XW UT WOS:000261847900003 PM 18937103 ER PT J AU Sloan, DM Feinstein, BA Marx, BP AF Sloan, Denise M. Feinstein, Brian A. Marx, Brian P. TI The durability of beneficial health effects associated with expressive writing SO ANXIETY STRESS AND COPING LA English DT Article DE expressive writing; written disclosure; stress; anxiety; depression; physical health ID WRITTEN EMOTIONAL DISCLOSURE; ANXIETY STRESS SCALES; DEPRESSIVE SYMPTOMS; BOOSTER SESSIONS; PSYCHOMETRIC PROPERTIES; RANDOMIZED-TRIAL; PHYSICAL HEALTH; SELF-REGULATION; IMMUNE FUNCTION; PSYCHONEUROIMMUNOLOGY AB This study examined the durability of benefits associated with expressive writing. Sixty-eight college undergraduates completed measures of physical and psychological health at the beginning of their first year and were then randomized to either an expressive writing or a control writing condition. Changes in physical health, psychological health (i.e., depression, stress, and anxiety), and academic performance were assessed two, four, and six months later. Findings indicated that participants assigned to the expressive writing condition reported less depression symptom severity at the two-month follow-up assessment relative to participants assigned to the control condition. However, these symptom reductions were not observed at any of the subsequent follow-up assessments. No significant changes were reported for physical health complaints, stress symptoms, anxiety symptoms, or academic performance. These findings suggest that, among first-year college students, expressive writing may provide some short-term relief for certain symptoms. C1 [Sloan, Denise M.; Feinstein, Brian A.; Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Sloan, Denise M.; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM dsloan@bu.edu OI Sloan, Denise/0000-0002-0962-478X FU NIMH NIH HHS [L30 MH072216, R03 MH068223] NR 46 TC 9 Z9 9 U1 3 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2009 VL 22 IS 5 BP 509 EP 523 DI 10.1080/10615800902785608 PG 15 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 492LF UT WOS:000269657900003 PM 19333797 ER PT J AU Hula, WD Hula, SNA Doyle, PJ AF Hula, William D. Hula, Shannon N. Austermann Doyle, Patrick J. TI A preliminary evaluation of the reliability and validity of a self-reported communicative functioning item pool SO APHASIOLOGY LA English DT Article CT 38th Annual Clinical Aphasiology Conference CY MAY 27-JUN 01, 2008 CL Jackson Hole, WY DE Assessment; Aphasia; Psychometrics ID QUALITY-OF-LIFE; STROKE SURVIVORS; RASCH ANALYSIS; SCALE; RATINGS; BURDEN AB Background: Item banking, an approach to test development based in item response theory (IRT), is beginning to be applied to the measurement of communicative functioning in aphasia. This approach involves calibrating a set of test items responding to a particular latent trait to a common measurement scale. One method for validating such scales is to examine the degree to which obtained item calibration estimates agree with a priori item rankings based on theory or expert opinion. Aims: The purpose of this study was to evaluate the utility of magnitude estimation (ME) procedures for validating item banks containing self-reported functional performance items, and to make a preliminary analysis of the validity of a proposed item pool for measuring self-reported communicative functioning in aphasia. Methods Procedures: A total of 14 raters made ME ratings of physical and communicative functioning items. These ratings were evaluated for their intra and inter-observer reliability and, for subsets of the items, their correspondence with previously published IRT calibration estimates was also evaluated. Outcomes Results: Intra-rater reliability was moderate to high, and inter-rater reliability was high. Correspondence with IRT calibrations was high for physical items, and moderate for communication items. The distribution of ME ratings for the communication items was negatively skewed. Conclusions: ME procedures have utility for investigating the validity of functional performance items. The results suggest that communicative functioning may have a more complex latent structure than physical functioning, and that the proposed item pool might benefit from the inclusion of additional items at the lower end of the scale. C1 [Hula, William D.; Hula, Shannon N. Austermann; Doyle, Patrick J.] Dept Vet Affairs Med Ctr, Pittsburgh, PA USA. [Hula, William D.; Doyle, Patrick J.] Univ Pittsburgh, Pittsburgh, PA USA. RP Hula, WD (reprint author), Ctr Geriatr Res Educ & Clin, VA Pittsburgh Healthcare Syst, 7180 Highland Dr,132A-H Pittsburgh, Pittsburgh, PA 15206 USA. EM William.hula@va.gov NR 27 TC 2 Z9 2 U1 1 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2009 VL 23 IS 7-8 BP 783 EP 796 AR PII 909565759 DI 10.1080/02687030802526064 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 468QR UT WOS:000267835400002 ER PT J AU McAllister, T Bachrach, A Waters, G Michaud, J Caplan, D AF McAllister, Tara Bachrach, Asaf Waters, Gloria Michaud, Jennifer Caplan, David TI Production and comprehension of unaccusatives in aphasia SO APHASIOLOGY LA English DT Article CT 38th Annual Clinical Aphasiology Conference CY MAY 27-JUN 01, 2008 CL Jackson Hole, WY DE Unaccusative verbs; Argument structures; Movement constructions ID SENTENCE PRODUCTION; AGRAMMATIC APHASIA; BROCAS APHASIA; LANGUAGE; DEFICITS; VERBS; CUES AB Background: Recent studies have reported impairments in the production of sentences containing unaccusative verbs (e.g., The ball bounced down the street) in agrammatic patients. In these sentences, the subject is the theme of the verb, resulting in a non-standard order of thematic roles (often called non-canonical thematic role order). Aims: We tested the hypothesis that aphasic patients would be affected by these features of unaccusatives in both production and comprehension, and that they would show similar deficits in sentences with unaccusative verbs and passive sentences, which also have non-canonical thematic role order. Methods Procedures: Single-word naming, sentence production, and sentence-picture matching tasks were administered to a group of 9 aphasic participants and 12 age- and education-matched control participants. Outcomes Results: The aphasic patients performed less well than the controls, and there were effects of the presence of movement in both groups and an interaction between group and sentence type in the sentence production task. Conclusions: These findings support the view that non-canonical thematic role order makes action naming, sentence production, and sentence comprehension more difficult, and that aphasic patients are more affected by the demands of these tasks than controls. C1 [McAllister, Tara; Bachrach, Asaf] MIT, Cambridge, MA 02139 USA. [McAllister, Tara; Waters, Gloria] Boston Univ, Boston, MA 02215 USA. [Michaud, Jennifer; Caplan, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McAllister, T (reprint author), MIT Linguist & Philosophy, 77 Massachusetts Ave,Bldg 32-D808, Cambridge, MA 02139 USA. EM mcallis@mit.edu NR 25 TC 15 Z9 15 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2009 VL 23 IS 7-8 BP 989 EP 1004 AR PII 912006664 DI 10.1080/02687030802669518 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 468QR UT WOS:000267835400017 ER PT J AU Sung, JE McNeil, MR Pratt, SR Dickey, MW Hula, WD Szuminsky, NJ Doyle, PJ AF Sung, Jee Eun McNeil, Malcolm R. Pratt, Sheila R. Dickey, Michael Walsh Hula, William D. Szuminsky, Neil J. Doyle, Patrick J. TI Verbal working memory and its relationship to sentence-level reading and listening comprehension in persons with aphasia SO APHASIOLOGY LA English DT Article CT 38th Annual Clinical Aphasiology Conference CY MAY 27-JUN 01, 2008 CL Jackson Hole, WY DE Working memory; Aphasia; Sentence comprehension; Aphasia severity ID INDIVIDUAL-DIFFERENCES; CAPACITY; ADULTS; TASK AB Background: Working memory (WM) has gained recent attention as a cognitive construct that may account for language comprehension deficits in persons with aphasia (PWA) (Caspari, Parkinson, LaPointe, Katz, 1998; Martin, Kohen, Kalinyak-Fliszar, 2008; Wright, Downey, Gravier, Love, Shapiro, 2007). However, few studies have investigated individual differences in performance on sentence comprehension tasks as a function of WM capacity in PWA when WM demands are manipulated. Aims: The purposes of the current study were: (1) to examine the relationships among verbal WM, sentence comprehension, and severity of impairment in PWA and (2) to investigate the differential performance of high versus low verbal WM groups on sentence comprehension tasks in which task demands were manipulated by the length of the sentence stimuli, complexity of syntactic structure, and by presentation method which varied the time over which the linguistic material was available for computation. Methods Procedures: A total of 20 PWA were divided into high and low WM groups based on a listening version of a WM sentence span task. Each participant completed a listening version (CRTT) and three reading versions (CRTT-R) of the Computerised Revised Token Test as the sentence comprehension tasks. Outcomes Results: The WM task significantly predicted performance on the CRTT conditions in which information was only temporarily available, thereby imposing greater WM demands on sentence comprehension. The verbal WM task was significantly correlated with aphasia severity and a principal components analysis revealed that the WM task, overall aphasia severity, and overall reading impairment level loaded on a single factor with 76% of shared variance. The low WM group's performance was significantly lower than the high WM group on the CRTT subtests with syntactically more complex structures and on the CRTT conditions with temporally restricted presentation methods. Conclusions: This verbal WM task was significantly and moderately correlated with the overall severity of aphasia as well as with both listening and reading sentence comprehension. The WM group differences emerged only in sentence comprehension tasks with greater WM demands. These results are consistent with the notion that WM effects are most evident when WM capacity is sufficiently taxed by the task demands (e.g., Caplan Waters, 1999; Just Carpenter, 1992). C1 [Sung, Jee Eun] Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Sung, JE (reprint author), Univ Pittsburgh, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. EM jee311@gmail.com RI Pratt, Sheila/H-7139-2013; OI Dickey, Michael Walsh/0000-0002-9068-3313 NR 25 TC 18 Z9 18 U1 1 U2 13 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2009 VL 23 IS 7-8 BP 1040 EP 1052 AR PII 909574662 DI 10.1080/02687030802592884 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 468QR UT WOS:000267835400021 ER PT J AU Yang, C Yang, S Wood, KB Hornicek, FJ Schwab, JH Fondren, G Mankin, H Duan, ZF AF Yang, Cao Yang, Shuhua Wood, Kirkham B. Hornicek, Francis J. Schwab, Joseph H. Fondren, Gertrude Mankin, Henry Duan, Zhenfeng TI Multidrug resistant osteosarcoma cell lines exhibit deficiency of GADD45 alpha expression SO APOPTOSIS LA English DT Article DE GADD45 alpha; Multidrug resistance; Osteosarcoma; Apoptosis ID DRUG-RESISTANCE; COLORECTAL-CANCER; OSTEOGENIC-SARCOMA; INDUCED APOPTOSIS; CARCINOMA CELLS; DOWN-REGULATION; FAMILY-MEMBERS; CHEMOTHERAPY; ACTIVATION; SUPPRESSION AB To identify apoptosis genes involved in the multidrug resistance of osteosarcoma, a multidrug resistant human osteosarcoma cell line (U-2 OS MR) was established. Apoptosis gene microarray analysis demonstrated that GADD45 alpha was significantly induced in U-2 OS cells after exposure to paclitaxel (P < 0.0001). However, the induction of GADD45 alpha did not occur in U-2 OS MR cells. Subsequent analysis by Western blot confirmed that the expression of GADD45 alpha could be significantly induced by paclitaxel and doxorubicin in U-2 OS cells but not in U-2 OS MR cells. Furthermore, the paclitaxel or doxorubicin treated U-2 OS and KH OS cells have a higher percentage of apoptotic cells when compared with U-2 OS MR and KH OS R2 cells treated with the same drugs. When GADD45 alpha was transfected into U-2 OS MR or KH OS R2 and expressed, the cells became more sensitive to chemotherapeutic drugs. These results suggest that GADD45 alpha may play a role in drug-induced apoptosis, as well as multidrug resistance in osteosarcoma cells. C1 [Yang, Cao; Wood, Kirkham B.; Hornicek, Francis J.; Schwab, Joseph H.; Fondren, Gertrude; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Yang, Cao; Hornicek, Francis J.; Schwab, Joseph H.; Fondren, Gertrude; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Yang, Cao; Yang, Shuhua] Huazhong Univ Sci & Technol, Dept Orthopaed Surg, Union Hosp, Tongji Med Coll, Wuhan 430022, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM zduan@partners.org FU National Cancer Institute; NIH (Nanotechnology Platform Partnership) [R01-CA119617]; Gaetagno and Wechsler FX Dr. C. Yang is supported through a grant from the Chinese Council of Scholarship. Dr. Z. Duan is supported, in part, through a grant from the National Cancer Institute, NIH (Nanotechnology Platform Partnership), R01-CA119617. Support has also been provided by the Gaetagno and Wechsler funds. NR 36 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JAN PY 2009 VL 14 IS 1 BP 124 EP 133 DI 10.1007/s10495-008-0282-x PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 387LW UT WOS:000261954700011 PM 19052873 ER PT S AU Derdak, Z Garcia, TA Baffy, G AF Derdak, Zoltan Garcia, Tamako A. Baffy, Gyorgy BE Erhardt, P Toth, A TI Detection of Uncoupling Protein-2 (UCP2) As a Mitochondrial Modulator of Apoptosis SO APOPTOSIS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE UCP2; Mitochondria; Oxidative stress; Superoxide; Mitochondrial isolation; Submitochondrial fractionation; Digitonin; Alkali treatment; Immunohistochemistry; Apoptosis ID OXIDATIVE STRESS; EXPRESSION; OVEREXPRESSION; DEATH; CELLS; DYSFUNCTION; REVEALS; OBESITY; GENE; MICE AB There is an increasing evidence that Uncoupling protein-2 (UCP2), a recently identified molecular sensor and Suppressor of mitochondrial reactive oxygen species (ROS), plays an important role in regulating apoptosis in different cell systems. A great technical difficulty that many groups have encountered is the reliable detection of endogenously or exogenously expressed UCP2 protein. The goal of this chapter is to introduce the reader to techniques that we have successfully used over the years to detect UCP2 protein in various Mouse and human specimens. These techniques include mitochondrial isolation and submitochondrial fractionation followed by Western blotting and UCP2 immunohistochemistry. We find that sample preparation is a key to success and it allows one to produce relevant and important data using commercially available antibodies. C1 [Derdak, Zoltan; Garcia, Tamako A.; Baffy, Gyorgy] Brown Med Sch, Div Gastroenterol, Providence, RI 02912 USA. [Derdak, Zoltan; Garcia, Tamako A.; Baffy, Gyorgy] Brown Med Sch, Liver Res Ctr, Providence, RI USA. [Derdak, Zoltan; Garcia, Tamako A.; Baffy, Gyorgy] Rhode Isl Hosp, Providence, RI USA. [Baffy, Gyorgy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Baffy, Gyorgy] VA Boston Healthcare Syst, Boston, MA USA. RP Derdak, Z (reprint author), Brown Med Sch, Div Gastroenterol, Providence, RI 02912 USA. FU NCRR NIH HHS [RR-17695]; NIDDK NIH HHS [DK-61890] NR 27 TC 7 Z9 7 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-016-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 559 BP 205 EP 217 DI 10.1007/978-1-60327-017-5_15 D2 10.1007/978-1-60327-017-5 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY96 UT WOS:000269656100015 PM 19609759 ER PT J AU Olson, CK Kutner, LA Baer, L Beresin, EV Warner, DE Nicholi, AM AF Olson, Cheryl K. Kutner, Lawrence A. Baer, Lee Beresin, Eugene V. Warner, Dorothy E. Nicholi, Armand M., II TI M-Rated Video Games and Aggressive or Problem Behavior Among Young Adolescents SO APPLIED DEVELOPMENTAL SCIENCE LA English DT Article ID MEDIA VIOLENCE; TRAIT ANGER; QUESTIONNAIRE; PARENTS; YOUTH; PLAY; EXPOSURE; CHILDREN; RISK; BOYS AB This research examined the potential relationship between adolescent problem behaviors and amount of time spent with violent electronic games. Survey data were collected from 1,254 7th and 8th grade students in two states. A odoseo of exposure to Mature-rated games was calculated using Entertainment Software Rating Board ratings of titles children reported playing oa lot in the past six months,o and average days per week of video game play. Analyses were conducted using simultaneous logistic regression for binary outcome variables, and simultaneous multiple linear regression for continuous outcome variables, controlling for a series of potential confounders. M-rated game dose predicted greater risk for bullying (p.01) and physical fights (p.001), but not for delinquent behaviors or being a victim of bullies. When analyzed separately, these associations became weaker for boys and stronger for girls. C1 [Olson, Cheryl K.] Massachusetts Gen Hosp, Ctr Mental Hlth & Media, Boston, MA 02114 USA. RP Olson, CK (reprint author), Massachusetts Gen Hosp, Ctr Mental Hlth & Media, Wang 812,Parkman St, Boston, MA 02114 USA. EM cheryl_olson@hms.harvard.edu RI Liang, Ting-chih/A-8858-2010 NR 72 TC 16 Z9 16 U1 5 U2 45 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1088-8691 J9 APPL DEV SCI JI Appl. Dev. Sci. PY 2009 VL 13 IS 4 BP 188 EP 198 AR PII 916185024 DI 10.1080/10888690903288748 PG 11 WC Psychology, Developmental SC Psychology GA 515ZL UT WOS:000271511300003 ER PT J AU Allen, DN Goldstein, G Caponigro, JM Donohue, B AF Allen, Daniel N. Goldstein, Gerald Caponigro, Janelle M. Donohue, Bradley TI The Effects of Alcoholism Comorbidity on Neurocognitive Function Following Traumatic Brain Injury SO APPLIED NEUROPSYCHOLOGY LA English DT Article DE alcoholism; Halstead-Reitan Neuropsychological Battery; traumatic brain injury ID YOUNG-ADULTS; ABUSE; SCHIZOPHRENIA; INTOXICATION; CONSUMPTION; DYSFUNCTION; LEVEL AB Alcoholism and traumatic brain injury (TBI) often produce neuropsychological deficits. However, the extent and manner by which these factors interact is unclear. In this study, it was hypothesized that alcoholism would have compounding cognitive effects in individuals with TBI and alcoholism. Participants were divided into three groups, including a patient comparison (PC) group and groups with TBI with or without alcoholism histories. Participants were administered the Wechsler Adult Intelligence Scale-Revised and major components of the Halstead-Reitan Neuropsychological Test Battery. Comparing the groups on test performance, the TBI groups performed significantly worse than the PC group but did not significantly differ from each other. Thus, the effects of TBI on cognitive function overshadow preexisting deficits from the alcoholism. C1 [Allen, Daniel N.; Donohue, Bradley] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. [Goldstein, Gerald; Caponigro, Janelle M.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Allen, DN (reprint author), Univ Nevada, Dept Psychol, 4505 Maryland Pkwy, Las Vegas, NV 89154 USA. EM daniel.allen@unlv.edu NR 30 TC 3 Z9 3 U1 2 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0908-4282 J9 APPL NEUROPSYCHOL JI Appl. Neuropsychol. PY 2009 VL 16 IS 3 BP 186 EP 192 DI 10.1080/09084280903098687 PG 7 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA 500LD UT WOS:000270301000007 PM 20183171 ER PT J AU Moghadam-Kia, S Chilek, K Gaines, E Costner, M Rose, M Okawa, J Werth, VP AF Moghadam-Kia, Siamak Chilek, Katherine Gaines, Elizabeth Costner, Melissa Rose, Mathew Okawa, Joyce Werth, Victoria P. TI A Cutaneous Lupus Erythematosus Database: Review of The First 116 Prospectively Enrolled Patients SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Meeting Abstract C1 [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Moghadam-Kia, Siamak; Chilek, Katherine; Gaines, Elizabeth; Rose, Mathew; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD JAN PY 2009 VL 301 IS 1 BP 45 EP 45 PG 1 WC Dermatology SC Dermatology GA 387QG UT WOS:000261966100050 ER PT J AU Weinstock, MA Bingham, SF Lew, RA Hall, R Eilers, D Kirsner, R Naylor, M Kalivas, J Cole, G Marcolivio, K Collins, J DiGiovanna, JJ Vertrees, JE AF Weinstock, Martin A. Bingham, Stephen F. Lew, Robert A. Hall, Russell Eilers, David Kirsner, Robert Naylor, Mark Kalivas, James Cole, Gary Marcolivio, Kimberly Collins, Joseph DiGiovanna, John J. Vertrees, Julia E. CA VATTC Trial Grp TI Topical Tretinoin Therapy and All-Cause Mortality SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; SQUAMOUS-CELL CARCINOMA; RETINOIC ACID SYNDROME; LUNG-CANCER; BETA-CAROTENE; SKIN-CANCER; PERCUTANEOUS-ABSORPTION; TRANSPLANT RECIPIENTS; PREVENTION; ISOTRETINOIN AB Objective: To evaluate the relation of topical tretinoin, a commonly used retinoid cream, with all-cause mortality in the Veterans Affairs Topical Tretinoin Chemoprevention Trial (VATTC). The planned outcome of this trial was risk of keratinocyte carcinoma, and systemic administration of certain retinoid compounds has been shown to reduce risk of this cancer but has also been associated with increased mortality risk among smokers. Design: The VATTC Trial was a blinded randomized chemoprevention trial, with 2- to 6-year follow-up. Oversight was provided by multiple independent committees. Setting: US Department of Veterans Affairs medical centers. Patients: A total of 1131 veterans were randomized. Their mean age was 71 years. Patients with a very high estimated short-term risk of death were excluded. Interventions: Application of tretinoin, 0.1%, or vehicle control cream twice daily to the face and ears. Main Outcome Measures: Death, which was not contemplated as an end point in the original study design. Results: The intervention was terminated 6 months early because of an excessive number of deaths in the tretinoin-treated group. Post hoc analysis of this difference revealed minor imbalances in age, comorbidity, and smoking status, all of which were important predictors of death. After adjusting for these imbalances, the difference in mortality between the randomized groups remained statistically significant. Conclusions: We observed an association of topical tretinoin therapy with death, but we do not infer a causal association that current evidence suggests is unlikely. C1 [Weinstock, Martin A.; Marcolivio, Kimberly] VA Med Ctr, Dermatoepidemiol Unit, Providence, RI 02908 USA. [Weinstock, Martin A.; DiGiovanna, John J.] Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA. [Weinstock, Martin A.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Bingham, Stephen F.; Collins, Joseph] VA Maryland Hlth Care Syst, Cooperat Studies Program, Perry Point, MD USA. [Lew, Robert A.] VA Boston Hlth Care Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Hall, Russell] Duke Univ, VA Med Ctr, Div Dermatol, Dept Med,Sch Med, Durham, NC USA. [Eilers, David] Edward Hines Jr VA Med Ctr, Dept Dermatol, Hines, IL USA. [Kirsner, Robert] Univ Miami, Miller Sch Med, Dept Dermatol & Cutaneous Surg,VA Med Ctr, Dept Epidemiol & Publ Hlth,Sylvester Comprehens C, Miami, FL 33136 USA. [Naylor, Mark] VA Med Ctr, Oklahoma City, OK USA. [Kalivas, James] VA Med Ctr, Phoenix, AZ USA. [Cole, Gary] VA Med Ctr, Dept Dermatol, Long Beach, CA USA. [Vertrees, Julia E.] VA Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA. RP Weinstock, MA (reprint author), VA Med Ctr, Dermatoepidemiol Unit, 111D 830 Chalkstone Ave, Providence, RI 02908 USA. EM maw@brown.edu FU Cooperative Studies Program (CSP) of the Office of Research and Development; US Department of Veterans Affairs; American Cancer Society FX This study was supported by the Cooperative Studies Program (CSP) of the Office of Research and Development, US Department of Veterans Affairs, and the American Cancer Society. OrthoNeutrogena, a division of Ortho-McNeil Pharmaceutical, Inc, provided the tretinoin, 0.1%, and the vehicle creams. NR 25 TC 32 Z9 32 U1 1 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 JAN PY 2009 VL 145 IS 1 BP 18 EP 24 PG 7 WC Dermatology SC Dermatology GA 395YL UT WOS:000262559300003 PM 19153339 ER PT J AU Idriss, SZ Kvedar, JC Watson, AJ AF Idriss, Shereene Z. Kvedar, Joseph C. Watson, Alice J. TI The Role of Online Support Communities Benefits of Expanded Social Networks to Patients With Psoriasis SO ARCHIVES OF DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; DIGITAL DIVIDE; INTERNET; PREVALENCE; POPULATION; ARTHRITIS; DISEASE; ISSUES; WORLD AB Objective: To determine the demographics, usage patterns, attitudes, and experiences of online support site users. Design: Online survey. Patients: A total of 260 subjects recruited from 5 online psoriasis support groups. Main Outcome Measures: An exploratory analysis was performed to determine demographic and disease characteristics of online support site users. Perceived benefits were also documented. Results: The mean (SD) age of respondents was 40.1 (11.5) years ( range, 18-75 years), most (75.7%) were white, female (60.4%), and college educated (84.3%). Key factors associated with use of online support sites included availability of resources (95.3%), convenience (94.0%), access to good advice (91.0%), and the lack of embarrassment when dealing with personal issues (90.8%). The most common activities were posting messages (65.0%) and searching for information (63.1%). Nearly half of all respondents perceived improvements in their quality of life (49.5%) and psoriasis severity (41.0%) since joining the site. Intensity of participation in online support activities was associated with improved quality of life (P =. 002), but not with improvements in psoriasis severity. Conclusions: Our data demonstrate that psoriasis virtual communities offer users both a valuable educational resource and a source of psychological and social support. Such benefits could be further enhanced by physician engagement within these communities. C1 [Idriss, Shereene Z.; Kvedar, Joseph C.; Watson, Alice J.] Massachusetts Gen Hosp, Ctr Connected Hlth, Boston, MA 02114 USA. [Idriss, Shereene Z.; Kvedar, Joseph C.; Watson, Alice J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kvedar, Joseph C.; Watson, Alice J.] Harvard Univ, Sch Med, Boston, MA USA. RP Watson, AJ (reprint author), 25 New Chardon St,Suite 400D, Boston, MA 02114 USA. EM AJWatson@partners.org RI Gutowski, Emily/N-1491-2015 FU Center for Connected Health FX This study was supported by the Center for Connected Health. NR 40 TC 39 Z9 40 U1 0 U2 8 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 JAN PY 2009 VL 145 IS 1 BP 46 EP 51 PG 6 WC Dermatology SC Dermatology GA 395YL UT WOS:000262559300006 PM 19153342 ER PT J AU Gorman, MP Healy, BC Polgar-Turcsanyi, M Chitnis, T AF Gorman, Mark P. Healy, Brian C. Polgar-Turcsanyi, Mariann Chitnis, Tanuja TI Increased Relapse Rate in Pediatric-Onset Compared With Adult-Onset Multiple Sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RECURRENT EVENTS; NATURAL-HISTORY; CLINICAL-TRIALS; DISEASE; CHILDHOOD; PROGNOSIS; MS; INTERFERON-BETA-1A AB Objective: To investigate whether or not the disparity in disease progression in those with pediatric-onset compared with adult-onset multiple sclerosis ( MS) is due to differences in relapse rates. Design: Inception cohort. Mean follow-up times were 3.67 ( standard deviation, 1.64) and 3.98 (standard deviation, 1.17) years in the pediatric and adult groups, respectively. Setting: Comprehensive MS centers. Patients: Patients with relapsing-remitting MS who were seen at the pediatric and adult MS centers at Massachusetts General and Brigham and Women's Hospitals, respectively, 12 months or less from onset of first symptom in July 2001 or later and were followed up for 12 months or longer. One hundred ten patients with adult-onset and 21 patients with pediatric-onset MS were included. Three eligible patients with adult-onset MS were excluded owing to incomplete records. Main Outcome Measure: Annualized relapse rates were compared between pediatric-onset and adult-onset patients using the proportional means model. Results: The annualized relapse rate in the pediatric-onset group was significantly higher than that in the adult-onset group (1.13 vs 0.40; P <. 001) with an adjusted rate ratio of 2.81 (95% confidence interval, 2.07-3.81). When we controlled for time spent undergoing disease-modifying treatment in the analysis, the difference between the groups remained highly significant ( adjusted rate ratio, 2.82; 95% confidence interval, 2.08-3.83; P <. 001). When age at disease onset was treated as a continuous variable, a highly significant association between age and relapse rate was observed ( P <. 001). Conclusions: Relapses are more frequent in patients with pediatric-onset compared with adult-onset MS in the disease-modifying treatment era. This finding suggests that patients with pediatric-onset MS experience a more inflammatory disease course than patients with adult onset of the disease. C1 [Gorman, Mark P.; Chitnis, Tanuja] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Gorman, Mark P.; Healy, Brian C.; Polgar-Turcsanyi, Mariann] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA. RP Chitnis, T (reprint author), Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, ACC-708,55 Fruit St, Boston, MA 02114 USA. EM tchitnis@partners.org FU Pediatric Multiple Sclerosis Centers of Excellence; National Multiple Sclerosis Society FX This study was supported by the Pediatric Multiple Sclerosis Centers of Excellence Grant from the National Multiple Sclerosis Society ( Dr Chitnis). Dr Gorman is supported by a National Multiple Sclerosis Society ( Central New England Chapter) Clinical Fellowship. NR 38 TC 121 Z9 123 U1 1 U2 6 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 JAN PY 2009 VL 66 IS 1 BP 54 EP 59 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 393UM UT WOS:000262398900006 PM 19139299 ER PT J AU Patel, PV FitzMaurice, E Nandigam, K Auluck, P Viswanathan, A Goldstein, JN Rosand, J Greenberg, SM Smith, EE AF Patel, Pratik V. FitzMaurice, Emilie Nandigam, Kaveer Auluck, Pavan Viswanathan, Anand Goldstein, Joshua N. Rosand, Jonathan Greenberg, Steven M. Smith, Eric E. TI Association of Subdural Hematoma With Increased Mortality in Lobar Intracerebral Hemorrhage SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; ARTERIAL ORIGIN; SUBARACHNOID HEMORRHAGE; CRITERIA; WARFARIN; RISK AB Objective: To determine the prevalence of subdural hematoma (SDH) in patients presenting with primary non-traumatic lobar intracerebral hemorrhage (ICH) and characteristics associated with the presence of SDH. Design: Retrospective analysis of data collected in a prospective cohort study. Setting: Hospital. Patients: Consecutive sample of 200 patients with primary lobar ICH and 75 patients with deep hemispheric ICH. Main Outcome Measures: Presence of SDH and mortality. Results: Subdural hematoma was present in 40 of 200 patients (20%) with primary lobar ICH. By contrast, SDH was not present in any of 75 consecutive patients with deep hemispheric ICH ( P <. 001 for comparison with lobar ICH). Intracerebral hemorrhage volume higher than 60 cm(3) was the only independent predictor of SDH ( odds ratio [ OR], 2.69; 95% confidence interval [CI], 1.14-6.34; P=. 02). Subdural hematoma thickness more than 5 mm was an independent predictor of increased 30-day mortality ( OR, 7.60; 95% CI, 1.86-30.99; P=. 005) after controlling for other factors including ICH volume. Further analysis showed that the effect of SDH on mortality depended on ICH volume, with larger odds for mortality in those with low ICH volume ( OR, 12.85; 95% CI, 2.42-68.23; P=. 003 for those with ICH volume < 30 cm3). Cerebral amyloid angiopathy was present in 8 of 9 patients with pathological specimens. Conclusions: Nontraumatic SDH frequently accompanies primary lobar ICH and is associated with higher 30-day mortality, particularly when the ICH volume is relatively low. Rupture of an amyloid-laden leptomeningeal vessel, with extravasation into the brain parenchyma and subdural space, may be the pathogenic mechanism. C1 [Patel, Pratik V.; FitzMaurice, Emilie; Nandigam, Kaveer; Viswanathan, Anand; Rosand, Jonathan; Greenberg, Steven M.; Smith, Eric E.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Auluck, Pavan] Massachusetts Gen Hosp, Neuropathol Serv, Dept Pathol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM eesmith@partners.org RI Auluck, Pavan/A-1160-2010; Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016 OI Smith, Eric/0000-0003-3956-1668; FU National Institute of Neurological Disorders and Stroke; National Institute of Aging; American Heart Association FX This work was supported by grant funding from the National Institute of Neurological Disorders and Stroke ( Drs Smith and Rosand), National Institute of Aging ( Dr Greenberg), and American Heart Association ( Dr Rosand). NR 29 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2009 VL 66 IS 1 BP 79 EP 84 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 393UM UT WOS:000262398900010 PM 19139303 ER PT J AU Klein, JP Cohen, AB Kimberly, WT Shah, AS Leiderman, YI Cestari, DM Dinkin, MJ AF Klein, Joshua P. Cohen, Adam B. Kimberly, W. Taylor Shah, Ankoor S. Leiderman, Yannek I. Cestari, Dean M. Dinkin, Marc J. TI Diffusion-Weighted Magnetic Resonance Imaging of Bilateral Simultaneous Optic Nerve Infarctions SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID NEUROPATHY C1 [Klein, Joshua P.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Klein, JP (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM jpklein@partners.org NR 4 TC 15 Z9 15 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 JAN PY 2009 VL 66 IS 1 BP 132 EP 133 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 393UM UT WOS:000262398900020 PM 19139313 ER PT J AU Boudoux, C Leuin, SC Oh, WY Suter, MJ Desjardins, AE Vakoc, BJ Bouma, BE Hartnick, CJ Tearney, GJ AF Boudoux, Caroline Leuin, Shelby C. Oh, Wang Yuhl Suter, Melissa J. Desjardins, Adrien E. Vakoc, Benjamin J. Bouma, Brett E. Hartnick, Christopher J. Tearney, Guillermo J. TI Optical Microscopy of the Pediatric Vocal Fold SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 02-04, 2008 CL Orlando, FL SP Amer Soc Pediat Otolaryngol ID ENCODED CONFOCAL MICROSCOPY; COHERENCE TOMOGRAPHY; IN-VIVO; HIGH-SPEED; LAMINA PROPRIA; LASER; CANCER; EXPERIENCE; EPITHELIUM; MICROFLAP AB Objectives: To compare and contrast 4 optical imaging techniques for evaluating the developing microstructure of the pediatric vocal fold and to identify the optimal strategy for in vivo imaging. Design: Prospective study. Setting: Academic medical center. Patients: A total of 6 laryngeal specimens: 5 pediatric (ages 10 months to 16 years) (4 from cadavers and 1 from a living patient immediately after laryngectomy) and 1 cadaveric young adult specimen (age, 23 years). Intervention: Sequential noninvasive optical imaging of pediatric vocal fold specimens using optical frequency domain imaging (OFDI), angle-resolved OFDI (AR-OFDI), spectrally encoded confocal microscopy (SECM), and full-field optical coherence microscopy (FF-OCM), followed by fixation, sectioning, and histologic analysis of the same specimen for comparison. Main Outcome Measure: Correlation between the microstructure observed using the 4 noninvasive optical imaging techniques and with the results of histopathologic analysis for the same specimen. Results: A successful in vivo imaging technique for developmental assessment of the pediatric vocal fold would include visualization of distinct layers (epithelium, lamina propria, and muscularis mucosa) and allow for identification of the individual cells composing the layers. The OFDI and AR-OFDI techniques provide a global assessment of the microstructure of the pediatric vocal fold to a depth of 1200 mu m but lack the ability to distinguish cellular and subcellular structures. The FF-OCM technique allows for visualization with improved cellular detail (1-mu m resolution), but the image acquisition speed is too slow for clinical use. The SECM technique has a faster acquisition rate and shows good cellular and subcellular detail to a depth of 250 mu m. Conclusions: The OFDI and SECM techniques were identified as promising and complementary candidates for in vivo cellular and subcellular imaging of the epithelium, basement membrane, and lamina propria of the pediatric vocal fold. To further validate the clinical potential of these techniques, a handheld SECM probe has been developed and demonstrated for in vivo evaluation of the pediatric vocal fold. C1 [Leuin, Shelby C.; Hartnick, Christopher J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Boudoux, Caroline; Oh, Wang Yuhl; Suter, Melissa J.; Desjardins, Adrien E.; Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Boudoux, Caroline; Desjardins, Adrien E.; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu RI Oh, Wang-Yuhl/C-2055-2011; Boudoux, Caroline/A-6399-2012 NR 49 TC 10 Z9 10 U1 0 U2 4 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 JAN PY 2009 VL 135 IS 1 BP 53 EP 64 PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 395XI UT WOS:000262556400009 PM 19153308 ER PT J AU White, WM Randolph, GW Hartnick, CJ Cunningham, MJ AF White, W. Matthew Randolph, Gregory W. Hartnick, Christopher J. Cunningham, Michael J. TI Recurrent Laryngeal Nerve Monitoring During Thyroidectomy and Related Cervical Procedures in the Pediatric Population SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 27-30, 2005 CL Las Vegas, NV SP Amer Soc Pediat Otolaryngol ID PATENT DUCTUS-ARTERIOSUS; PARATHYROID SURGERY; ADOLESCENTS; CHILDREN; IDENTIFICATION; EXPERIENCE; CARCINOMA; PARALYSIS; ANOMALIES AB Objectives: To gather data on, and assess the applicability of, intraoperative recurrent laryngeal nerve (RLN) monitoring during thyroidectomy and related cervical procedures in children and adolescents. Recurrent laryngeal nerve trauma is one of the most serious complications of surgery in the anterior neck compartment. Numerous studies have demonstrated the utility of intraoperative monitoring of the RLN in adult thyroid surgery to prevent such injury. Although the risk of RLN injury is reportedly higher in the pediatric population, little data exist regarding the use of intraoperative RLN monitoring in children and adolescents. Design: Retrospective case series review. Setting: A pediatric otolaryngology practice in a tertiary care hospital. Patients: Five patients undergoing surgical excision of thyroid neoplasms or branchial pouch anomalies. Interventions: During surgical excision, intraoperative RLN monitoring was performed with use of the Xomed NIM II monitor and Xomed RLN monitoring endotracheal tube, which allow for both passive and stimulation-evoked electromyographic monitoring of the thyroarytenoid muscle. Main Outcome Measures: True vocal fold mobility as assessed by postoperative flexible laryngoscopy. Results: Intraoperative RLN monitoring was performed successfully for up to 4 hours. Such monitoring facilitated the identification of the RLN and was predictive of the subsequent presence or absence of postoperative RLN paresis. Conclusions: Intraoperative RLN monitoring can be a useful tool during cervical procedures that place the RLN at risk in children and adolescents. As has been demonstrated in adults, it is a safe and reliable technique that can be predictive of and may lessen the risk of RLN morbidity in this younger patient population. C1 [Cunningham, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Michael_Cunningham@meei.harvard.edu NR 24 TC 14 Z9 15 U1 0 U2 6 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 JAN PY 2009 VL 135 IS 1 BP 88 EP 94 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 395XI UT WOS:000262556400014 PM 19153313 ER PT J AU Brigger, MT Misdraji, J Hardy, SC Hartnick, CJ AF Brigger, Matthew T. Misdraji, Joseph Hardy, Stephen C. Hartnick, Christopher J. TI Eosinophilic Esophagitis in Children A Pathologic or Clinicopathologic Diagnosis? SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 02-04, 2008 CL Orlando, FL SP Amer Soc Pediat Otolaryngol ID GASTROESOPHAGEAL-REFLUX; ALLERGIC ESOPHAGITIS; FEATURES; ADULTS; PATHOGENESIS; ASSOCIATION; THERAPY; MUCOSA; DIET AB Objective: To determine the accuracy of histopathologic diagnosis in distinguishing eosinophilic esophagitis (EE) from gastroesophageal reflux disease (GERD) in children with upper aerodigestive symptoms. Design: Masked review of esophageal biopsy findings and comparison with each child's established clinical diagnosis. Setting: A tertiary care multidisciplinary aerodigestive center. Patients: Children were selected from a longitudinal database of all children referred for upper aerodigestive symptoms who underwent a comprehensive evaluation between September 1, 2004, and September 1, 2007. Three groups were recognized based on clinical presentation, initial histologic review, and therapeutic response: children with EE, GERD, or neither. Intervention: Review of esophageal biopsy findings by a pathologist masked to the child's clinical or previous pathologic diagnosis. Main Outcome Measure: Masked histopathologic diagnosis of EE, GERD, or neither. Results: Medical records from 31 patients were reviewed ( 11 children with EE, 10 with GERD, and 10 with neither). Diagnostic concurrence between the masked pathologic diagnosis and the established clinicopathologic diagnosis was 64% in children with EE, 70% in children with GERD, and 100% in children with neither. The 4 cases of EE that did not concur were misclassified as GERD when esophageal specimens were evaluated by histopathologic means alone. A clinicopathologic schema for EE developed by gastroenterologists accurately identified 82% of children with EE. Conclusions: The distinction between EE and GERD cannot be reliably made on histopathologic evidence alone in children with upper aerodigestive symptoms. Despite the recent gastroenterology consensus statement regarding the clinicopathologic diagnosis of EE, children with primary airway symptoms in whom EE is suspected represent a diagnostic dilemma. C1 [Brigger, Matthew T.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Misdraji, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Hardy, Stephen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gastroenterol & Nutr, Boston, MA USA. RP Brigger, MT (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM matt.brigger@alumni.vanderbilt.edu NR 22 TC 7 Z9 7 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 JAN PY 2009 VL 135 IS 1 BP 95 EP 100 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 395XI UT WOS:000262556400015 PM 19153314 ER PT J AU Lester, SC Bose, S Chen, YY Connolly, JL de Baca, ME Fitzgibbons, PL Hayes, DF Kleer, C O'Malley, FP Page, DL Smith, BL Weaver, DL Winer, E AF Lester, Susan C. Bose, Shikha Chen, Yunn-Yi Connolly, James L. de Baca, Monica E. Fitzgibbons, Patrick L. Hayes, Daniel F. Kleer, Celina O'Malley, Frances P. Page, David L. Smith, Barbara L. Weaver, Donald L. Winer, Eric CA Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Ductal Carcinoma In Situ of the Breast SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NUYS PROGNOSTIC INDEX; TERM-FOLLOW-UP; MARGIN ASSESSMENT; LOCAL RECURRENCE; 6TH EDITION; CONSERVING THERAPY; TUMOR SIZE; CANCER; DCIS; CONSERVATION C1 [Lester, Susan C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Connolly, James L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [Winer, Eric] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bose, Shikha] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Chen, Yunn-Yi] UCSF Med Ctr, Dept Pathol, San Francisco, CA USA. [de Baca, Monica E.] Phys Lab, Sioux Falls, SD USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Hayes, Daniel F.] Univ Michigan, Med Ctr, Dept Med Oncol, Ann Arbor, MI USA. [Kleer, Celina] Univ Michigan, Med Ctr, Dept Pathol, Ann Arbor, MI 48109 USA. [O'Malley, Frances P.] Univ Toronto, Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [Page, David L.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Weaver, Donald L.] Univ Vermont, Vermont Reg Canc Ctr, Burlington, VT USA. RP Lester, SC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM slester@partners.org OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 48 TC 55 Z9 57 U1 2 U2 5 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2009 VL 133 IS 1 BP 15 EP 25 PG 11 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 391XK UT WOS:000262267300003 PM 19123730 ER PT J AU Crothers, BA Moriarty, AT Fatheree, LA Booth, CN Tench, WD Wilbur, DC AF Crothers, Barbara A. Moriarty, Ann T. Fatheree, Lisa A. Booth, Christine N. Tench, William D. Wilbur, David C. TI Appeals in Gynecologic Cytology Proficiency Testing Review and Analysis of Data From the 2006 College of American Pathologists Gynecologic Cytology Proficiency Testing Program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INTERLABORATORY COMPARISON PROGRAM; SQUAMOUS INTRAEPITHELIAL LESION; CERVICOVAGINAL CYTOLOGY; VALIDATION AB Context.-In 2006, 9643 participants took the initial College of American Pathologists (CAP) Proficiency Test (PT). Failing participants may appeal results on specific test slides. Appeals are granted if 3 referee pathologists do not unanimously agree on the initial reference diagnosis in a masked review process. Objectives.-To investigate causes of PT failures, subsequent appeals, and appeal successes in 2006. Design.-Appeals were examined, including patient demographic information, Centers for Medicare and Medicaid Services category ( A, B, C, or D), exact reference diagnosis, examinees per appeal, examinee's Centers for Medicare and Medicaid Services category, referee's Centers for Medicare and Medicaid Services category, slide preparation type, and slide field validation rate. Results.-There was a 94% passing rate for 2006. One hundred fifty-five examinees (1.6%) appealed 86 slides of all preparation types. Forty-five appeals (29%) were granted on 21 slides; 110 appeals (72%) were denied on 65 slides. Reference category D and B slides were most often appealed. The highest percentage of granted appeals occurred in category D (35% slides; 42% of participants) and the lowest occurred in category B (9% slides; 8% of participants). The field validation rate of all appealed slides was greater than 90%. Conclusions.-Despite rigorous field validation of slides, 6% of participants failed. Thirty percent of failing participants appealed; most appeals involved misinterpretation of category D as category B. Referees were never unanimous in their agreement with the participant. The participants and referees struggled with the reliability and reproducibility of finding rare cells, "overdiagnosis'' of benign changes, and assigning the morphologically dynamic biologic changes of squamous intraepithelial lesions to static categories. C1 [Crothers, Barbara A.] Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. [Crothers, Barbara A.] Walter Reed Army Med Ctr, Lab Serv, Washington, DC 20307 USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Pathol, Indianapolis, IN USA. [Fatheree, Lisa A.] Coll Amer Pathologists, Dept Cytol Surveys, Northfield, IL USA. [Booth, Christine N.] Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. [Tench, William D.] Palomar Med Ctr, Escondido, CA USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Crothers, BA (reprint author), Walter Reed Army Med Ctr, Dept Pathol, MCHL UAP Ward 47,6900 Georgia Ave NW, Washington, DC 20307 USA. EM barbara.crothers@na.amedd.army.mil NR 15 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2009 VL 133 IS 1 BP 44 EP 48 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 391XK UT WOS:000262267300007 PM 19123735 ER PT J AU Kwarciak, AM Sisto, SA Yarossi, M Price, R Komaroff, E Boninger, ML AF Kwarciak, Andrew M. Sisto, Sue Ann Yarossi, Mathew Price, Robert Komaroff, Eugene Boninger, Michael L. TI Redefining the Manual Wheelchair Stroke Cycle: Identification and Impact of Nonpropulsive Pushrim Contact SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Biomechanics; Rehabilitation; Wheelchair ID SPINAL-CORD-INJURY; SHOULDER JOINT KINETICS; UPPER EXTREMITY PAIN; 2 SPEEDS; PROPULSION BIOMECHANICS; MECHANICAL EFFICIENCY; SEAT POSITION; USERS; INDIVIDUALS; PARAPLEGIA AB Objectives: To create a comprehensive definition of the manual wheelchair stroke cycle, which includes multiple periods of pushrim contact, and to show its improved clinical benefit to wheelchair propulsion analyses. Design: Cross-sectional biomechanics study. Setting: Three motion analysis laboratories. Participants: Persons (N=54) with paraplegia who use a manual wheelchair. Interventions: Not applicable. Main Outcome Measures: Pushrim forces, axle moments, and contact angles measured during wheelchair propulsion. Results: Total force on the pushrim was used to define pushrim contact and positive axle moment was used to identify the included period of propulsive contact. During most strokes, periods of nonpropulsive contact existed before and after propulsive contact. Within these periods, braking moments were applied to the pushrim, resulting in negative power output, or power loss. Including nonpropulsive data decreased mean stroke moment and power. The magnitude and the angle over which braking moments and power loss occurred increased with wheel speed. Mean braking moment and power loss within the initial contact period were significantly (P<.001) related to stroke pattern. Conclusions: The proposed definition of the stroke cycle provides a thorough and practical description of wheelchair propulsion. Researchers and clinicians should use this definition to understand and minimize the impact of nonpropulsive contact throughout the stroke. C1 [Kwarciak, Andrew M.; Sisto, Sue Ann; Yarossi, Mathew; Komaroff, Eugene] Kessler Med Rehabil Res & Educ Ctr, W Orange, NJ 07052 USA. [Sisto, Sue Ann; Komaroff, Eugene] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. [Sisto, Sue Ann] SUNY Stony Brook, Dept Rehabil Sci, Stony Brook, NY 11794 USA. [Price, Robert] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Boninger, Michael L.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn & Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Med Ctr Hlth Syst, Pittsburgh, PA USA. RP Kwarciak, AM (reprint author), Kessler Med Rehabil Res & Educ Ctr, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM akwarciak@kesslerfoundation.net OI Boninger, Michael/0000-0001-6966-919X FU National Institute on Disability and Rehabilitation Research [H133A011107]; Henry H. Kessler Foundation. FX Supported by the National Institute on Disability and Rehabilitation Research (grain no. H133A011107) and by the Henry H. Kessler Foundation. NR 37 TC 20 Z9 20 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2009 VL 90 IS 1 BP 20 EP 26 DI 10.1016/j.apmr.2008.07.013 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 397IY UT WOS:000262657600004 PM 19154825 ER PT J AU Muehlenkamp, JJ Williams, KL Gutierrez, PM Claes, L AF Muehlenkamp, Jennifer J. Williams, Kirsten L. Gutierrez, Peter M. Claes, Laurence TI Rates of Non-Suicidal Self-Injury in High School Students Across Five Years SO ARCHIVES OF SUICIDE RESEARCH LA English DT Article DE adolescents; deliberate self-harm; high-school students; non-suicidal self-injury; suicide ID SUICIDE ATTEMPTS; COMMUNITY SAMPLE; RISK-FACTORS; ADOLESCENTS; HARM; BEHAVIOR; TRENDS AB It is believed that the rate of non-suicidal self-injury (NSSI) among high school students is increasing. However, no known research has examined the rates of NSSI among non-clinical, high school samples of adolescents across several years. The current study utilized archival data from five academic years [2001 to 2005 (N = 1393)] to address this limitation by examining the lifetime prevalence rates of NSSI in urban high school students within the Midwestern United States. Results indicate a significant difference in rates across years by gender. Females showed a significant increase in their rates of NSSI compared to males, who showed a significant decline, during the last 3 years of the study. Implications of these findings for school personnel and directions for future research discussed. C1 [Muehlenkamp, Jennifer J.] Univ Wisconsin, Dept Psychol, Eau Claire, WI 54702 USA. [Muehlenkamp, Jennifer J.; Williams, Kirsten L.] Univ N Dakota, Grand Forks, ND 58201 USA. [Gutierrez, Peter M.] Mental Illness Res Educ & Clin Ctr, Denver VA Med Ctr, Denver, CO USA. [Claes, Laurence] Catholic Univ Louvain, B-3000 Louvain, Belgium. RP Muehlenkamp, JJ (reprint author), Univ Wisconsin, Dept Psychol, 277 Hibbard Hall, Eau Claire, WI 54702 USA. EM muehlejj@uwec.edu NR 25 TC 20 Z9 21 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1381-1118 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PY 2009 VL 13 IS 4 BP 317 EP 329 DI 10.1080/13811110903266368 PG 13 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 579XO UT WOS:000276410900002 PM 19813109 ER PT J AU Amstadter, AB Koenen, KC Ruggiero, KJ Acierno, R Galea, S Kilpatrick, DG Gelernter, J AF Amstadter, Ananda B. Koenen, Karestan C. Ruggiero, Kenneth J. Acierno, Ron Galea, Sandro Kilpatrick, Dean G. Gelernter, Joel TI Variation in RGS2 is Associated with Suicidal Ideation in an Epidemiological Study of Adults Exposed to the 2004 Florida Hurricanes SO ARCHIVES OF SUICIDE RESEARCH LA English DT Article DE gene association; RGS2; suicidal ideation; suicide; trauma ID POPULATION GROUP ASSIGNMENT; POSTTRAUMATIC-STRESS; GENE POLYMORPHISMS; SOCIAL SUPPORT; RISK-FACTORS; BEHAVIOR; ANXIETY; MARKERS; MODULATORS; GENOTYPE AB This study examined whether rs4606, a single nucleotide polymorphism (SNP) in the translated region at the 3' end of RGS2, was related to suicidal ideation in an epidemiologic sample of adults living in areas affected by the 2004 Florida hurricanes. An epidemiologic sample of residents of Florida was recruited via random digit-dial procedures after the 2004 Florida hurricanes; participants were interviewed about suicidal ideation, hurricane exposure, and social support. Participants who returned buccal DNA samples via mail (n = 607) were included here. Rs4606 in RGS2 was associated with increased symptoms of current suicidal ideation (p < 0.01). Each "C" allele was associated with 5.59 times increased risk of having current ideation. No gene-by-environment interactions were found, perhaps due to low power. RGS2 rs4606 is related to risk of current suicidal ideation in stressor-exposed adults. C1 [Amstadter, Ananda B.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ruggiero, Kenneth J.; Acierno, Ron; Kilpatrick, Dean G.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.; Acierno, Ron] Ralph Johnson VA Med Ctr, Charleston, SC USA. [Galea, Sandro] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. RP Amstadter, AB (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,2-S, Charleston, SC 29425 USA. EM amstadt@musc.edu FU NIDA NIH HHS [K24 DA015105, K24 DA15105]; NIMH NIH HHS [MH07055, K08 MH070627-06, K08 MH070627, MH078928, R01 MH078928, R01 MH078928-01A1, K08-MH070627, R21 MH074469-02, MH05220, F32 MH083469-01, F32 MH083469]; PHS HHS [083469] NR 31 TC 6 Z9 6 U1 3 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1381-1118 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PY 2009 VL 13 IS 4 BP 349 EP 357 DI 10.1080/13811110903266541 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 579XO UT WOS:000276410900005 PM 19813112 ER PT J AU Regenbogen, SE Ehrenfeld, JM Lipsitz, SR Greenberg, CC Hutter, MM Gawande, AA AF Regenbogen, Scott E. Ehrenfeld, Jesse M. Lipsitz, Stuart R. Greenberg, Caprice C. Hutter, Matthew M. Gawande, Atul A. TI Utility of the Surgical Apgar Score Validation in 4119 Patients SO ARCHIVES OF SURGERY LA English DT Article ID PERIOPERATIVE RISK; BLOOD-PRESSURE; CLASSIFICATION; QUALITY; SYSTEM; COMPLICATIONS; HANDWRITTEN; RECORDS AB Objectives: To confirm the utility of a 10-point Surgical Apgar Score to rate surgical outcomes in a large cohort of patients. Design: Using electronic intraoperative records, we calculated Surgical Apgar Scores during a period of 2 years (July 1, 2003, through June 30, 2005). Setting: Major academic medical center. Patients: Systematic sample of 4119 general and vascular surgery patients enrolled in the National Surgical Quality Improvement Program surgical outcomes database at a major academic medical center. Main Outcome Measures: Incidence of major postoperative complications and/or death within 30 days of surgery. Results: Of 1441 patients with scores of 9 to 10, 72 (5.0%) developed major complications within 30 days, including 2 deaths (0.1%). By comparison, among 128 patients with scores of 4 or less, 72 developed major complications (56.3%; relative risk, 11.3; 95% confidence interval, 8.6-14.8; P<.001), of whom 25 died (19.5%; relative risk, 140.7; 95% confidence interval, 33.7-587.4; P<.001). The 3-variable score achieves C statistics of 0.73 for major complications and 0.81 for deaths. Conclusions: The Surgical Apgar Score provides a simple, immediate, objective means of measuring and communicating patient outcomes in surgery, using data routinely available in any setting. The score can be effective in identifying patients at higher- and lower-than average likelihood of major complications and/or death after surgery and may be useful for evaluating interventions to prevent poor outcomes. C1 [Regenbogen, Scott E.; Greenberg, Caprice C.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Regenbogen, Scott E.; Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ehrenfeld, Jesse M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Lipsitz, Stuart R.; Greenberg, Caprice C.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Regenbogen, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM sregenbogen@partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140 FU Harvard Medical Institutions; Agency for Healthcare Research and Quality [T32-HS000020] FX This research was supported by a grant from the Risk Management Foundation of the Harvard Medical Institutions. Dr Regenbogen was also supported by Kirschstein National Research Service Award T32-HS000020 from the Agency for Healthcare Research and Quality. NR 31 TC 51 Z9 52 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JAN PY 2009 VL 144 IS 1 BP 30 EP 36 PG 7 WC Surgery SC Surgery GA 395VK UT WOS:000262551400007 PM 19153322 ER PT J AU Manning-Tobin, JJ Moore, KJ Seimon, TA Bell, SA Sharuk, M Alvarez-Leite, JI de Winther, MPJ Tabas, I Freeman, MW AF Manning-Tobin, Jennifer J. Moore, Kathryn J. Seimon, Tracie A. Bell, Susan A. Sharuk, Maia Alvarez-Leite, Jacqueline I. de Winther, Menno P. J. Tabas, Ira Freeman, Mason W. TI Loss of SR-A and CD36 Activity Reduces Atherosclerotic Lesion Complexity Without Abrogating Foam Cell Formation in Hyperlipidemic Mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE scavenger receptor; atherosclerosis; apoptosis; necrosis; inflammation ID LOW-DENSITY-LIPOPROTEIN; SCAVENGER-RECEPTOR-A; MACROPHAGE APOPTOSIS; THERAPEUTIC IMPLICATIONS; PLAQUE STABILITY; MURINE MODELS; LIPID UPTAKE; PATHWAYS; ATHEROGENESIS; PHAGOCYTOSIS AB Objective-The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis and in the regulation of inflammatory signaling pathways, including those leading to lesional macrophage apoptosis and plaque necrosis. To test the impact of deleting these receptors, we generated Apoe(-/-) mice lacking both SR-A and CD36 and fed them a Western diet for 12 weeks. Methods and Results-We analyzed atheroma in mice, assessing lesion size, foam cell formation, inflammatory gene expression, apoptosis, and necrotic core formation. Aortic root atherosclerosis in Apoe(-/-) Cd36(-/-) Msr1(-/-) mice, as assessed by morphometry, electron microscopy, and immunohistochemistry, showed no decrease in lesion area or in vivo foam cell formation when compared to Apoe(-/-) mice. However, Apoe(-/-) Cd36(-/-) Msr1(-/-) lesions showed reduced expression of inflammatory genes and morphological analysis revealed a approximate to 30% decrease in macrophage apoptosis and a striking approximate to 50% decrease in plaque necrosis in aortic root lesions of these mice. Conclusions-Although targeted deletion of SR-A and CD36 does not abrogate macrophage foam cell formation or substantially reduce atherosclerotic lesion area in Apoe(-/-) mice, loss of these pathways does reduce progression to more advanced necrotic lesions. These data suggest that targeted inhibition of these pathways in vivo may reduce lesional inflammation and promote plaque stability. (Arterioscler Thromb Vasc Biol. 2009; 29: 19-26.) C1 [Manning-Tobin, Jennifer J.; Moore, Kathryn J.; Bell, Susan A.; Sharuk, Maia; Alvarez-Leite, Jacqueline I.; Freeman, Mason W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. [Freeman, Mason W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Seimon, Tracie A.; Tabas, Ira] Columbia Univ, Dept Med, New York, NY USA. [Tabas, Ira] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Tabas, Ira] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA. [Alvarez-Leite, Jacqueline I.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [de Winther, Menno P. J.] Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Mol Genet, Maastricht, Netherlands. RP Freeman, MW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. EM freeman@molbio.mgh.harvard.edu RI de Winther, Menno/E-8721-2012; OI de Winther, Menno/0000-0002-4038-6636; Moore, kathryn/0000-0003-2505-2547 FU NIH [HL45098, RR20345, AG20255, HL75662, HL57560]; American Heart Association Scientist Development [0735594T]; CNPq [200140/2006-0] FX This work was supported by NIH grants HL45098 and RR20345 (M. W. F.), AG20255 (K. J. M.), HL75662 and HL57560 (I. T.), an American Heart Association Scientist Development Grant 0735594T (T. A. S.) and grant # 200140/2006-0 from CNPq (J. L.). NR 39 TC 123 Z9 127 U1 0 U2 8 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 JAN PY 2009 VL 29 IS 1 BP 19 EP U51 DI 10.1161/ATVBAHA.108.176644 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 385EV UT WOS:000261797200006 PM 18948635 ER PT J AU Gaffo, AL Edwards, NL Saag, KG AF Gaffo, Angelo L. Edwards, N. Lawrence Saag, Kenneth G. TI Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link? SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID SERUM URIC-ACID; INTIMA-MEDIA THICKNESS; ALL-CAUSE MORTALITY; GLOMERULAR HYPERTENSION; BLOOD-PRESSURE; LONG-TERM; INDEPENDENT PREDICTOR; METABOLIC SYNDROME; OXIDATIVE STRESS; KIDNEY-FUNCTION AB An association between high levels of serum urate and cardiovascular disease has been proposed for many decades. However, it was only recently that compelling basic science data, small clinical trials, and epidemiological studies have provided support to the idea of a true causal effect. In this review we present recently published data that study the association between hyperuricemia and selected cardiovascular diseases, with a final conclusion about the possibility of this association being causal. C1 [Saag, Kenneth G.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Edwards, N. Lawrence] Univ Florida, Div Rheumatol, Gainesville, FL 32610 USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Saag, KG (reprint author), Univ Alabama, Div Clin Immunol & Rheumatol, FOT 820,1530 3rd Ave S, Birmingham, AL 35294 USA. EM ksaag@uab.edu FU Takeda; Savient; Merck FX Research grants were received from Takeda, Savient and Merck. NR 51 TC 30 Z9 32 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 4 AR 240 DI 10.1186/ar2761 PG 7 WC Rheumatology SC Rheumatology GA 508MU UT WOS:000270936400011 PM 19725932 ER PT J AU Hueber, W Tomooka, BH Batliwalla, F Li, WT Monach, PA Tibshirani, RJ Van Vollenhoven, RF Lampa, J Saito, K Tanaka, Y Genovese, MC Klareskog, L Gregersen, PK Robinson, WH AF Hueber, Wolfgang Tomooka, Beren H. Batliwalla, Franak Li, Wentian Monach, Paul A. Tibshirani, Robert J. Van Vollenhoven, Ronald F. Lampa, Jon Saito, Kazuyoshi Tanaka, Yoshiya Genovese, Mark C. Klareskog, Lars Gregersen, Peter K. Robinson, William H. TI Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID CONCOMITANT METHOTREXATE; MONOCLONAL-ANTIBODY; CLINICAL-TRIALS; INFLIXIMAB; PROTEIN; ETANERCEPT; TNF; IMPROVEMENT; ADALIMUMAB; REGISTRY AB Introduction Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis ( RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers. Methods Here we present a multi-step proteomics approach using arthritis antigen arrays, a multiplex cytokine assay, and conventional ELISA, with the objective to identify a biomarker signature in three ethnically diverse cohorts of RA patients treated with the anti-TNF therapy etanercept. Results We identified a 24-biomarker signature that enabled prediction of a positive clinical response to etanercept in all three cohorts ( positive predictive values 58 to 72%; negative predictive values 63 to 78%). Conclusions We identified a multi-parameter protein biomarker that enables pretreatment classification and prediction of etanercept responders, and tested this biomarker using three independent cohorts of RA patients. Although further validation in prospective and larger cohorts is needed, our observations demonstrate that multiplex characterization of autoantibodies and cytokines provides clinical utility for predicting response to the anti-TNF therapy etanercept in RA patients. C1 [Hueber, Wolfgang; Tomooka, Beren H.; Genovese, Mark C.; Robinson, William H.] Stanford Univ, Div Rheumatol & Immunol, Dept Med, Stanford, CA 94305 USA. [Hueber, Wolfgang; Tomooka, Beren H.; Robinson, William H.] VA Palo Alto Hlth Care Syst, GRECC, Palo Alto, CA 94304 USA. [Batliwalla, Franak; Li, Wentian; Gregersen, Peter K.] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Monach, Paul A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Monach, Paul A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tibshirani, Robert J.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Van Vollenhoven, Ronald F.; Lampa, Jon; Klareskog, Lars] Karolinska Inst, SE-17176 Stockholm, Sweden. [Saito, Kazuyoshi; Tanaka, Yoshiya] Univ Occupat & Environm Hlth, Dept Internal Med 1, Kitakyushu, Fukuoka 8078555, Japan. RP Hueber, W (reprint author), Stanford Univ, Div Rheumatol & Immunol, Dept Med, 269 Campus Dr,Mail Code 5166, Stanford, CA 94305 USA. EM whueber@stanford.edu OI Li, Wentian/0000-0003-1155-110X; Klareskog, Lars/0000-0001-9601-6186 FU Arthritis Foundation Investigator Award; NIH NHLBI [N01 HV 28183]; NIH NIAMS [AI069160]; Veterans Affairs Health Care System FX The authors are grateful to Maya BenBarak for technical help with data analysis, to Markus Britschgi for critically reading the manuscript, and to the members of the Robinson laboratory for scientific input. The present work was funded by an Arthritis Foundation Investigator Award, NIH NHLBI contract N01 HV 28183, NIH NIAMS AI069160, and Veterans Affairs Health Care System funding to WHR. NR 29 TC 53 Z9 59 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 3 AR R76 DI 10.1186/ar2706 PG 13 WC Rheumatology SC Rheumatology GA 484BW UT WOS:000269019300042 PM 19460157 ER PT J AU Karlson, EW Chibnik, LB McGrath, M Chang, SC Keenan, BT Costenbader, KH Fraser, PA Tworoger, S Hankinson, SE Lee, IM Buring, J De Vivo, I AF Karlson, Elizabeth W. Chibnik, Lori B. McGrath, Monica Chang, Shun-Chiao Keenan, Brendan T. Costenbader, Karen H. Fraser, Patricia A. Tworoger, Shelley Hankinson, Susan E. Lee, I-Min Buring, Julie De Vivo, Immaculata TI A prospective study of androgen levels, hormone-related genes and risk of rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID BREAST-CANCER RISK; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PROGESTERONE-RECEPTOR GENE; RANDOMIZED CONTROLLED-TRIAL; GENOME-WIDE ASSOCIATION; LOW-DOSE ASPIRIN; POSTMENOPAUSAL WOMEN; PRIMARY PREVENTION; FUNCTIONAL POLYMORPHISM; CARDIOVASCULAR-DISEASE AB Introduction Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. We conducted a case-control study nested within two prospective studies to determine the associations between plasma steroid hormones measured prior to RA onset and polymorphisms in the androgen receptor (AR), estrogen receptor 2 (ESR2), aromatase (CYP19) and progesterone receptor (PGR) genes and RA risk. Methods We genotyped AR, ESR2, CYP19, PGR SNPs and the AR CAG repeat in RA case-control studies nested within the Nurses' Health Study (NHS), NHS II (449 RA cases, 449 controls) and the Women's Health Study (72 cases, and 202 controls). All controls were matched on cohort, age, Caucasian race, menopausal status, and postmenopausal hormone use. We measured plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin in 132 pre-RA samples and 396 matched controls in the NHS cohorts. We used conditional logistic regression models adjusted for potential confounders to assess RA risk. Results Mean age of RA diagnosis was 55 years in both cohorts; 58% of cases were rheumatoid factor positive at diagnosis. There was no significant association between plasma DHEAS, total testosterone, or calculated free testosterone and risk of future RA. There was no association between individual variants or haplotypes in any of the genes and RA or seropositive RA, nor any association for the AR CAG repeat. Conclusions Steroid hormone levels measured at a single time point prior to RA onset were not associated with RA risk in this study. Our findings do not suggest that androgens or the AR, ESR2, PGR, and CYP19 genes are important to RA risk in women. C1 [Karlson, Elizabeth W.; Chibnik, Lori B.; Keenan, Brendan T.; Costenbader, Karen H.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Buring, Julie] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. [Tworoger, Shelley; Hankinson, Susan E.; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Chang, Shun-Chiao; Tworoger, Shelley; Hankinson, Susan E.; Lee, I-Min; Buring, Julie] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fraser, Patricia A.] Immune Dis Inst, Boston, MA 02115 USA. [Fraser, Patricia A.] Genzyme Corp, Cambridge, MA 02115 USA. [Lee, I-Min; Buring, Julie] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. RP Karlson, EW (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA. EM ekarlson@partners.org OI Tworoger, Shelley/0000-0002-6986-7046 FU NIH [R01 AR49880, CA87969, HL43851, HL 080467, CA47988, P60 AR047782, K24 AR0524-01, BIRCWH K12 HD051959]; Arthritis Foundation/American College of Rheumatology Arthritis Investigator; Katherine Swan Ginsburg Memorial Award FX The authors thank the participants in the NHS and the WHS cohorts for their dedication and continued participation in these longitudinal studies, and thank the staff of the NHS and WHS for their assistance with this project. The present work was supported by NIH grants R01 AR49880, CA87969, HL43851, HL 080467 CA47988, P60 AR047782, K24 AR0524-01 and BIRCWH K12 HD051959 (supported by NIMH, NIAID, NICHD, and OD). KHC is the recipient of an Arthritis Foundation/American College of Rheumatology Arthritis Investigator Award and a Katherine Swan Ginsburg Memorial Award. NR 69 TC 26 Z9 27 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 3 AR R97 DI 10.1186/ar2742 PG 12 WC Rheumatology SC Rheumatology GA 484BW UT WOS:000269019300063 PM 19555469 ER PT B AU Griffith, MH Asnis, PD AF Griffith, Matthew H. Asnis, Peter D. BE Gill, TJ TI Positioning and Set-Up SO ARTHROSCOPIC TECHNIQUES OF THE KNEE: A VISUAL GUIDE SE Visual Arthroscopy Series LA English DT Article; Book Chapter ID MONOPOLAR RADIOFREQUENCY DEVICES; THERMAL CHONDROPLASTY; KNEE ARTHROSCOPY; COMPARTMENT SYNDROME; CHONDROCYTE DEATH; IN-VITRO; ENERGY; BIPOLAR; TEMPERATURE; CARTILAGE C1 [Griffith, Matthew H.; Asnis, Peter D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Sports Med, Boston, MA 02115 USA. RP Griffith, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Sports Med, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-858-6 J9 VIS ARTHROSC SER PY 2009 BP 1 EP 12 PG 12 WC Orthopedics SC Orthopedics GA BKC79 UT WOS:000267778400001 ER PT B AU Wollman, L AF Wollman, Lisa BE Gill, TJ TI Anesthesia for Knee Surgery SO ARTHROSCOPIC TECHNIQUES OF THE KNEE: A VISUAL GUIDE SE Visual Arthroscopy Series LA English DT Article; Book Chapter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Wollman, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-858-6 J9 VIS ARTHROSC SER PY 2009 BP 15 EP 24 PG 10 WC Orthopedics SC Orthopedics GA BKC79 UT WOS:000267778400002 ER PT B AU Oh, LS Gill, TJ AF Oh, Luke S. Gill, Thomas. J. BE Gill, TJ TI Microfracture SO ARTHROSCOPIC TECHNIQUES OF THE KNEE: A VISUAL GUIDE SE Visual Arthroscopy Series LA English DT Article; Book Chapter C1 [Oh, Luke S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oh, LS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-858-6 J9 VIS ARTHROSC SER PY 2009 BP 63 EP 70 PG 8 WC Orthopedics SC Orthopedics GA BKC79 UT WOS:000267778400005 ER PT B AU Oh, LS Gill, TJ AF Oh, Luke S. Gill, Thomas J. BE Gill, TJ TI Single-Bundle Posterior Cruciate Ligament Reconstruction Arthroscopic Transtibial Technique SO ARTHROSCOPIC TECHNIQUES OF THE KNEE: A VISUAL GUIDE SE Visual Arthroscopy Series LA English DT Article; Book Chapter C1 [Oh, Luke S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oh, LS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-858-6 J9 VIS ARTHROSC SER PY 2009 BP 147 EP 169 PG 23 WC Orthopedics SC Orthopedics GA BKC79 UT WOS:000267778400012 ER PT B AU Parnes, N Rolf, RH Friedman, DJ Warner, JJP AF Parnes, Nata Rolf, Robert H. Friedman, Darren J. Warner, Jon J. P. BE David, TS Andrews, JR TI Arthroscopic Capsular Release SO ARTHROSCOPIC TECHNIQUES OF THE SHOULDER: A VISUAL GUIDE SE Visual Arthroscopy Series LA English DT Article; Book Chapter ID FROZEN SHOULDER; CONTRACTURE; REPAIR C1 [Parnes, Nata; Rolf, Robert H.; Warner, Jon J. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Friedman, Darren J.] Seaport Orthopaed Associates, New York, NY USA. RP Parnes, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-838-8 J9 VIS ARTHROSC SER PY 2009 BP 139 EP 146 PG 8 WC Orthopedics SC Orthopedics GA BKC77 UT WOS:000267777600012 ER PT S AU Metsis, V Huang, H Makedon, F Tzika, A AF Metsis, Vangelis Huang, Heng Makedon, Fillia Tzika, Aria BE ILiadis, L Vlahavas, I Bramer, M TI Heterogeneous Data Fusion to Type Brain Tumor Biopsies SO ARTIFICIAL INTELLIGENCE APPLICATIONS AND INNOVATIONS III SE International Federation for Information Processing LA English DT Proceedings Paper CT 5th IFIP Conference on Artificial Intelligence Applications and Innovations CY APR 23-25, 2009 CL Thessaloniki, GREECE SP IFIP ID MAGNETIC-RESONANCE SPECTROSCOPY; GLIOBLASTOMA-MULTIFORME; SURVIVAL AB Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources Such as gene ontology. Analysis of these data sets Could lead to better disease diagnosis, prognosis, treatment and drug discovery. In this paper, we use machine learning algorithms to create a novel framework to perform the heterogeneous data fusion oil both metabolic and molecular datasets, including state-of-the-art high-resolution magic angle spinning (HRMAS) proton (1H) Magnetic Resonance Spectroscopy and gene transcriptome profiling, to intact brain tumor biopsies and to identify different profiles of brain tumors. Our experimental results show Our novel framework outperforms any analysis using individual dataset. C1 [Metsis, Vangelis; Huang, Heng; Makedon, Fillia] Univ Texas Arlington, Arlington, TX 76019 USA. [Tzika, Aria] Massachusetts Gen Hosp, Harvard Med Sch, NMR Surg Lab, Dept Surg, Boston, MA USA. RP Metsis, V (reprint author), Univ Texas Arlington, Arlington, TX 76019 USA. EM vangjel.meci@mavs.uta.edu; heng@uta.edu; makedon@uta.edu; tzika@hms.harvard.edu NR 23 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-5736 BN 978-1-4419-0220-7 J9 INT FED INFO PROC PY 2009 BP 233 EP + PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BJG92 UT WOS:000265736800026 ER PT S AU Shin, JH Smith, D Swiniarski, R Dudek, FE White, A Staley, K Cios, KJ AF Shin, Joo-Heon Smith, Dave Swiniarski, Roman Dudek, F. Edward White, Andrew Staley, Kevin Cios, Krzysztof J. BE Combi, C Shahar, Y AbuHanna, A TI Analysis of EEG Epileptic Signals with Rough Sets and Support Vector Machines SO ARTIFICIAL INTELLIGENCE IN MEDICINE, PROCEEDINGS SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT 12th Conference on Artificial Intelligence in Medicine (AIME 2009) CY JUL 18-22, 2009 CL Verona, ITALY SP European Soc Artificial Intelligence Med DE epileptic seizures detection; medical signal processing; rough sets ID AUTOMATIC SEIZURE DETECTION; NEURAL-NETWORK; STRATEGIES; VALIDATION; ALGORITHMS; BRAIN; RATS AB Epilepsy, is a common chronic neurological disorder that impacts over 1% of the population. Animal models are used to better understand epilepsy, particularly the mechanisms and the basic for better antiepileptic therapies. For animal studies, the ability to identify, accurately seizures in electroencephalographic (EEG) recordings is critical, and the use of Computational tools is likely to play in important role. Electrical recording electrodes were implanted in rats before kaillate-induced status epilepticus (one in each hippocampus and one on the surface of the cortex), and EEG data were collected with radio-telemetry. Several data mining methods, such as wavelets, and neural net,works, were used to develop algorithms for detecting seizures. Rough sets, which were used as an additional feature selection technique in addition to the Daubechies wavelets and the FFTs, were also used in the detection algorithm. Compared with the seizure-at-once method by using the R.BF neural network classifier used earlier oil the same data [12], the new method achieved higher recognition rates (i.e., 9.1%). Furthermore, when the entire dataset was used, as compared to only 50% used earlier, preprocessing using wavelets, Principal Component Analysis, and rough sets in concert with Support Vector Machines resulted in accuracy of 94% in identifying epileptic seizures. C1 [Shin, Joo-Heon; Cios, Krzysztof J.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Smith, Dave; White, Andrew] Univ Colorado Denver, Denver, CO USA. [Swiniarski, Roman] San Diego State Univ, San Diego, CA USA. [Cios, Krzysztof J.] IITiS polish Acad sci, Gliwice, Poland. [Dudek, F. Edward] Univ Utah, Salt Lake City, UT 84112 USA. [Staley, Kevin] Massachusetts Gen Hosp, Massachusetts Harvard Med, Boston, MA USA. RP Shin, JH (reprint author), Virginia Commonwealth Univ, Richmond, VA 23284 USA. EM kcios@vcu.edu NR 24 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-02975-2 J9 LECT NOTES ARTIF INT PY 2009 VL 5651 BP 325 EP + PG 3 WC Computer Science, Artificial Intelligence; Engineering, Biomedical SC Computer Science; Engineering GA BKT59 UT WOS:000269199500045 ER PT B AU Kim, SP Simeral, JD Hochberg, LR Donoghue, JP Black, MJ AF Kim, Sung-Phil Simeral, John D. Hochberg, Leigh R. Donoghue, John P. Black, Michael J. GP IEEE TI Computer cursor control by motor cortical signals in humans with tetraplegia SO ASCC: 2009 7TH ASIAN CONTROL CONFERENCE, VOLS 1-3 LA English DT Proceedings Paper CT 7th Asian Control Conference (ASCC 2009) CY AUG 27-29, 2009 CL Hong Kong, PEOPLES R CHINA SP Asian Control Assoc, IEEE Control Sys Soc, Hong Kong Inst Engineers, Hong Kong Univ Sci & Technol, KC Wong Educ Fdn, Res Grant Council Hong Kong ID ARM MOVEMENTS; NEURAL ACTIVITY; CORTEX; DISCHARGE; DIRECTION; PATTERNS; VELOCITY AB A direct neural interface system (NIS) promises to provide communication and independence to persons with paralysis by harnessing intact motor cortical signals to enable controlling prosthetic devices. An intracortical NIS aims to achieve this by sensing extracellular neuronal signals through chronically implanted microelectrodes and by decoding the spiking activity of neurons into prosthetic control signals. In non-human primate studies, decoding has been performed by finding a relationship between neuronal signals and actual limb movements. However, such decoding approaches face challenges in the case of paralyzed persons where there is no true movement information. Specifically, we have focused on dealing with several key questions in decoding of neural activity in humans with paralysis: what movement parameters should be decoded?; which decoding algorithms lead to more accurate estimation of movement parameters?; how do we train decoding algorithms without observing actual movement parameters?; and how many control parameters can be decoded from a single neural ensemble? In this paper, we summarize our recent studies to address these questions to improve decoding performance, which enables a human with tetraplegia to drive a 2D computer cursor to an arbitrary position and execute a "click" on the area of interest. C1 [Kim, Sung-Phil; Black, Michael J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA. [Simeral, John D.; Hochberg, Leigh R.] Ctr Restorat & Regenerat, Dept Veterans Affairs Med, Med Rehabilitat R & D Serv, Providence, RI USA. [Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI USA. [Hochberg, Leigh R.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. [Donoghue, John P.] Cyberkinet Neurotechnol Syst Inc, Foxboro, MA 02035 USA. [Donoghue, John P.] Brown Univ, Providence, RI 02912 USA. RP Kim, SP (reprint author), Brown Univ, Dept Comp Sci, Providence, RI 02912 USA. EM spkim@cs.brown.edu; John_Simcral@brown.edu; Leigh_Hochberg@brown.edu; John_Donoghue@brown.edu FU MGH-Deane Institute; NIH/NINDS-Javits [NS-25074/NICHD-NCMRR, N01-HD-53403/NIBIB]; Dept. of Veterans Affairs; Rehabilitation RD Service; ONR [N00014-07-1-0803]; Cyberkinetics Neurotechnology Systems; Doris Duke Charitable Foundation; Katie Samson Foundation; National Center for Research Resources [C06-16549-01A1] FX This work was supported in part by MGH-Deane Institute, NIH/NINDS-Javits (NS-25074)/NICHD-NCMRR (N01-HD-53403)/NIBIB, Dept. of Veterans Affairs, Rehabilitation R&D Service, ONR (N00014-07-1-0803), Cyberkinetics Neurotechnology Systems, Inc., Doris Duke Charitable Foundation, Katie Samson Foundation, National Center for Research Resources (NCRR C06-16549-01A1). Disclosures: LRH: Clinical trial support, Cyberkinetics Neurotechnology Systems, Inc. (CYKN); JDS: Consultant, CYKN; JPD: prior Chief Scientific Officer and director, stock holdings, CYKN. NR 26 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-5440-2 PY 2009 BP 988 EP 993 PG 6 WC Automation & Control Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Automation & Control Systems; Computer Science GA BNF20 UT WOS:000274323100172 ER PT J AU Greene, R Shibuya, K Ando, T AF Greene, Reginald Shibuya, Kazutoshi Ando, Tsunihiro BE Latge, JP Steinbach, WJ TI Histology and Radiology SO ASPERGILLUS FUMIGATUS AND ASPERGILLOSIS LA English DT Article; Book Chapter ID INVASIVE PULMONARY ASPERGILLOSIS; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; AIR CRESCENT SIGN; HALO SIGN; PATHOLOGICAL CORRELATION; CLINICAL-SIGNIFICANCE; IMAGING FINDINGS; CYSTIC-FIBROSIS; AMPHOTERICIN-B; CASE SERIES C1 [Greene, Reginald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Shibuya, Kazutoshi; Ando, Tsunihiro] Toho Univ, Sch Med, Dept Surg Pathol, Ota Ku, Tokyo 1438541, Japan. RP Greene, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-552-3 PY 2009 BP 353 EP + PG 12 WC Microbiology; Mycology SC Microbiology; Mycology GA BOY46 UT WOS:000278059700028 ER PT J AU Camargo, CA Rowe, BH AF Camargo, Carlos A., Jr. Rowe, Brian H. BE Barnes, PJ Drazen, JM Rennard, SI Thomson, NC TI Asthma Exacerbations SO ASTHMA AND COPD: BASIC MECHANISMS AND CLINICAL MANAGEMENT, 2ND EDITION LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND TRIAL; CARE FOLLOW-UP; EMERGENCY-DEPARTMENT; PROSPECTIVE MULTICENTER; IPRATROPIUM BROMIDE; NEBULIZED ALBUTEROL; ACUTE BRONCHOSPASM; MAGNESIUM-SULFATE; ORAL MONTELUKAST C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. [Rowe, Brian H.] Capital Hlth, Edmonton, AB, Canada. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. NR 80 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092060-3 PY 2009 BP 775 EP 789 DI 10.1016/B978-0-12-374001-4.00064-X PG 15 WC Respiratory System SC Respiratory System GA BCT27 UT WOS:000311345000065 ER PT J AU Kuhlencordt, PJ Padmapriya, P Rutzel, S Schodel, J Hu, K Schafer, A Huang, PL Ertl, G Bauersachs, J AF Kuhlencordt, Peter J. Padmapriya, P. Ruetzel, S. Schoedel, J. Hu, K. Schaefer, A. Huang, P. L. Ertl, G. Bauersachs, J. TI Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice SO ATHEROSCLEROSIS LA English DT Article DE Nitric oxide; Endothelial vasodilator function; Ezetimibe; Atherosclerosis; Endothelial activation ID NITRIC-OXIDE SYNTHASE; CHOLESTEROL ABSORPTION INHIBITOR; CORONARY-HEART-DISEASE; SUPEROXIDE ANION PRODUCTION; LOW-DENSITY-LIPOPROTEIN; DOUBLE-KNOCKOUT MICE; APOLIPOPROTEIN-E; SMOOTH-MUSCLE; ACCELERATED ATHEROSCLEROSIS; ENDOTHELIAL FUNCTION AB Objective: Hypercholesterolemia is associated with decreased vascular nitric oxide bioavailability and deletion of endothelial nitric oxide synthase (eNOS) markedly accelerates atherosclerosis development in apolipoprotein E knockout (apoE ko) mice. The current study tests whether atheroprotection provided by a lipid lowering therapy with Ezetimibe depends on eNOS. Methods/results: ApoE ko and apoE/eNOS double ko (dko) mice received a high fat diet with or without 0.05% Ezetimibe. Ezetimibe significantly reduced plasma cholesterol concentrations and atherogenic lipoproteins in both genotypes to a similar extent. Moreover, the drug reduced vascular inflammation, as it significantly reduced vascular cell adhesion molecule-1 (VCAM-1) expression and vascular CD14 expression, a market for mononuclear cell infiltration. in both genotypes. Neither NOS protein expression nor vascular reactivity of aortic rings was changed in apoE ko mice following Ezetimibe treatment. Significant lesion reduction was seen in Ezetimibe-treated male and female apoE ko and apoE/eNOS dko animals (p <= 0.05). Interestingly, the drug-mediated additional atheroprotection in male apoE ko, compared to male eNOS dko mice. suggesting that lipid lowering does provide additional eNOS-dependent atheroprotection in this experimental group. Conclusion: Lipid lowering with Ezetimibe potently reduces atherosclerosis and vascular inflammation independent of eNOS. Moreover, Ezetimibe did not exert any effects on eNOS protein expression or enzyme activity. However, additional atheroprotection by Ezetimibe was observed in eNOS competent apoE ko mice, suggesting that some of the drug's anti-atherosclerotic effects are mediated by the eNOS pathway. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Kuhlencordt, Peter J.; Padmapriya, P.; Ruetzel, S.; Schoedel, J.; Hu, K.; Schaefer, A.; Ertl, G.; Bauersachs, J.] Univ Wurzburg, Univ Klinikum, Med Klin 1, Herz Kreislaufzentrum, D-97080 Wurzburg, Germany. [Huang, P. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Huang, P. L.] Harvard Univ, Sch Med, Boston, MA USA. RP Kuhlencordt, PJ (reprint author), Univ Wurzburg, Univ Klinikum, Med Klin 1, Herz Kreislaufzentrum, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM kuhlencord_p@klinik.uni-wuerzburg.de OI Schodel, Johannes/0000-0002-3587-8839 FU MSD; Essex Pharma GmbH; Deutsche-Forschungsgemeinschaft [KU-1206(1), 1206(2)]; IZKF-Wurzburg; National Institute of Neurological Disorders and Stroke (NINDS) [NS33335]; National Heart, Lung, and Blood Institute (NHLBI) [HL57818] FX This work was supported by a grant from MSD and Essex Pharma GmbH to P.K. and J.B. and from the Deutsche-Forschungsgemeinschaft (KU-1206(1) and 1206(2) and the IZKF-Wurzburg to P.K., the National Institute of Neurological Disorders and Stroke (NINDS, NS33335) and the National Heart, Lung, and Blood Institute (NHLBI, HL57818) to P.L.H. P.L.H. is an established investigator of the American Heart Association. Ezetimibe was supplied from Schering-Plough Research Institute. We thank Bruker BioSpin GmbH, Karlsruhe, Germany for the use of their ESR facility and Ms. G. Riehl, Mrs. A. Ganscher and Ms. M. Leutke for excellent technical assistance. NR 45 TC 23 Z9 26 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2009 VL 202 IS 1 BP 48 EP 57 DI 10.1016/j.atherosclerosis.2008.03.021 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 398JW UT WOS:000262729400009 PM 18479686 ER PT J AU Tian, L Luo, NL Klein, RL Chung, BH Garvey, WT Fu, YC AF Tian, Ling Luo, Nanlan Klein, Richard L. Chung, B. Hong Garvey, W. Timothy Fu, Yuchang TI Adiponectin reduces lipid accumulation in macrophage foam cells SO ATHEROSCLEROSIS LA English DT Article DE Adiponectin; Lipid accumulation; Macrophage foam cells; Atherosclerosis ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; PLASMA-PROTEIN ADIPONECTIN; ACTIVATED RECEPTOR-GAMMA; PPAR-GAMMA; CHOLESTEROL EFFLUX; METABOLIC SYNDROME; DEFICIENT MICE; ATHEROSCLEROSIS; DIFFERENTIATION AB Adiponectin is one of several, important metabolically active cytokines secreted from adipocytes. Low circulating levels of this adipokine have been associated epidemiologically with obesity. insulin resistance, type 11 diabetes, and cardiovascular disease. To determine if adiponectin can modulate lipid metabolism in macrophages, we expressed the adiponectin gene in human THP-1 macrophage foam Cells using a lentiviral vector expression system and demonstrated that macrophages transduced with the adiponectin gene had decreased lipid accumulation compared with control macrophages transduced with the LacZ gene. Macrophages transduced with the adiponectin gene also exhibited decreased oxidized low-density lipoprotein (oxLDL) uptake and increased HDL-mediated cholesterol efflux. Additional studies Suggest two potential mechanisms for the reduced lipid accumulation in these adiponectin-transduced macrophage foam cells. The first mechanism involves the PPAR gamma and LXR signaling pathways which up-regulate the expression of ABCA1 and promote lipid efflux front these cells. The second mechanism involves decreased lipid uptake and increased lipid hydrolysis which may result front decreased SR-AI and increased SR-BI and HSL gene activities in the transformed macrophage foam cells. We also demonstrated that the expression of two proatherogenic cytokines, MCP-1 and TNF alpha. were decreased in the adiponectin-transduced macrophage foam cells. These results suggest that adiponectin may modulate Multiple pathways of lipid metabolism in macrophages. Our Studies provide new insights into potential mechanisms of adiponectin-mediated alterations in lipid metabolism and macrophage foam cell formation which may impact the development of atherosclerosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Tian, Ling; Luo, Nanlan; Chung, B. Hong; Garvey, W. Timothy; Fu, Yuchang] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Klein, Richard L.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Klein, Richard L.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Fu, YC (reprint author), Univ Alabama, Dept Nutr Sci, Shelby Bldg 1213, Birmingham, AL 35294 USA. EM yfu@uab.edu RI Tian, Ling/J-6417-2012 FU National Institutes of Health [PO1-HL55782, DK38764, P20 RR16434]; Medical Research Service of the Department of Veterans Affairs; American Diabetes Association [1-07-RA-49] FX This work was supported by grants from the National Institutes of Health (PO1-HL55782, DK38764) and the Merit Review Program of the Medical Research Service of the Department of Veterans Affairs to WTG and RLK: by grants from National Institutes of Health (P20 RR16434) and American Diabetes Association (1-07-RA-49) to YF NR 30 TC 60 Z9 66 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2009 VL 202 IS 1 BP 152 EP 161 DI 10.1016/j.atherosclerosis.2008.04.011 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 398JW UT WOS:000262729400021 PM 18511057 ER PT J AU Orakzai, SH Nasir, K Blaha, M Blumenthal, RS Raggi, P AF Orakzai, Sarwar H. Nasir, Khurram Blaha, Michael Blumenthal, Roger S. Raggi, Paolo TI Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals SO ATHEROSCLEROSIS LA English DT Article DE Coronary artery calcium; Atherosclerosis; Lipoproteins; Cholesterol; Non-high-density lipoprotein cholesterol ID DENSITY-LIPOPROTEIN CHOLESTEROL; HEART-DISEASE; APOLIPOPROTEIN-B; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; RISK; ATHEROSCLEROSIS; PREDICTOR; MEN; ANGIOGRAPHY AB Background: Growing evidence shows that non-high-density lipoprotein cholesterol (Non-HDL-C) is a strong and independent predictor of cardiovascular disease (CVD). Few studies have assessed the association between traditional lipid measures and subclinical end points. In this study we analyzed the association of Non-HDL-C, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) with coronary artery calcium (CAC), a marker Of subclinical atherosclerosis. Methods: The study population consisted of 1611 consecutive asymptomatic individuals (67% men, mean ape: 53 +/- 10 years) referred to a single electron beam tomography (EBT) facility for CAC screening. Multivariate logistic regression was used to test the association between increasing quartiles of lipid levels and presence of CAC score (CACS) > 0 and CACS >= 100, with the lowest levels (first quartile) of lipid values as reference. Results: Overall CACS of 0, 1-99, 100-399 and >= 400, were observed in 35%, 44%, 12% and 9% of the Study subjects, respectively. The prevalence of CAC increased significantly across increasing quartiles of LDL-C, TG and Non-HDL-C (all p < 0.0001), whereas CACS was significantly lower across increasing quartiles of HDL-C (p < 0.001). In a multivariate model controlling for age, gender, race, cigarette smoking, hypertension. family history of coronary artery disease and obesity, there was a significant increase in the prevalence of CAC with increasing values of each lipid variable. In a multivariate model simultaneously controlling for increasing quartiles of the remaining lipid variables. only the association of Non-HDL-C with CACS > 0 remained statistically significant (p = 0.002). Similar results were observed with CACS >= 100 (p = 0.038). Conclusion In this study Non-HDL-C was more strongly associated with subclinical atherosclerosis than all other conventional lipid values. These data suggests that Non-HDL-C may be an important treatment target in primary prevention. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Raggi, Paolo] Emory Univ, Sch Med, Div Cardiol, Dept Med Cardiol, Atlanta, GA 30322 USA. [Orakzai, Sarwar H.] St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Dept Cardiol, Houston, TX USA. [Nasir, Khurram] Harvard Univ, Sch Med, Boston, MA USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac PET CT MRI Program, Boston, MA 02114 USA. [Blaha, Michael; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. RP Raggi, P (reprint author), Emory Univ, Sch Med, Div Cardiol, Dept Med Cardiol, 1365 Clifton Rd,AT-504, Atlanta, GA 30322 USA. EM praggi@emory.edu NR 27 TC 42 Z9 48 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2009 VL 202 IS 1 BP 289 EP 295 DI 10.1016/j.atherosclerosis.2008.03.014 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 398JW UT WOS:000262729400040 PM 18452924 ER PT J AU O'Malley, JT Merchant, SN Burgess, BJ Jones, DD Adams, JC AF O'Malley, Jennifer T. Merchant, Saumil N. Burgess, Barbara J. Jones, Diane D. Adams, Joe C. TI Effects of Fixative and Embedding Medium on Morphology and Immunostaining of the Cochlea SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Cochlea; Immunostaining; Celloidin; Temporal bone ID TEMPORAL BONE SECTIONS; ELECTRON-MICROSCOPY; CELLOIDIN SECTIONS; ANTIGEN RETRIEVAL; IMMUNOHISTOCHEMISTRY; PROTEINS AB The localization of proteins by immunostaining is a powerful method to investigate otologic disorders. However, the use of fixatives and embedding media (necessary for the preservation of morphology) can obscure antigens, making it difficult to perform immunoassays. We performed a systematic investigation of the effects of fixative and embedding medium on morphology and immunostaining of the mouse cochlea. Three different fixative solutions [4% formaldehyde (F), 4% formaldehyde + 1% acetic acid (FA), and 4% formaldehyde + 1% acetic acid + 0.1% glutaraldehyde (FGA)] and 3 different embedding media (paraffin, polyester wax, and celloidin) were used. Morphology was assessed using light microscopy. Immunostaining was studied using a panel of 6 antibodies (to prostaglandin D synthase, aquaporin 1, connective tissue growth factor, 200-kDa neurofilament, tubulin and Na(+), K(+)-ATPase). Preservation of morphology was suboptimal with paraffin, adequate with polyester wax and superb with celloidin. Immunostaining was successful using all 6 antibodies in all 3 fixatives and all 3 embedding media. While there were differences in strength of signal and localization of antigen between the 3 fixatives, overall, FA and FGA gave the most uniform results. For a given fixative and antibody, there was surprisingly little difference in the quality of immunostaining between celloidin and paraffin, while results in polyester wax were not as good in some cases. These results suggest that celloidin may be the embedding medium of choice for both morphological and pathological studies, including immunostaining when morphology must be optimized. Copyright (C) 2008 S. Karger AG, Basel C1 [O'Malley, Jennifer T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Merchant, Saumil N.; Adams, Joe C.] Harvard Univ, Sch Med, Boston, MA USA. RP O'Malley, JT (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Jennifer_O'Malley@meei.harvard.edu FU NIDCD [U24 DC0008559] FX This work was supported by funding from the NIDCD U24 DC0008559. We also thank Mr. Axel Eliasen and Mr. Lakshmi Mittal for support of our work. NR 19 TC 18 Z9 18 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2009 VL 14 IS 2 BP 78 EP 87 DI 10.1159/000158536 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 391CC UT WOS:000262209500002 PM 18827478 ER PT J AU Handzel, O Wang, HB Fiering, J Borenstein, JT Mescher, MJ Swan, EEL Murphy, BA Chen, ZQ Peppi, M Sewell, WF Kujawa, SG McKenna, MJ AF Handzel, Ophir Wang, Haobing Fiering, Jason Borenstein, Jeffrey T. Mescher, Mark J. Swan, Erin E. Leary Murphy, Brian A. Chen, Zhiqiang Peppi, Marcello Sewell, William F. Kujawa, Sharon G. McKenna, Michael J. TI Mastoid Cavity Dimensions and Shape: Method of Measurement and Virtual Fitting of Implantable Devices SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Mastoid dimension; Mastoid size measurement method; Implantable device ID EAR DRUG-DELIVERY AB Temporal bone implants can be used to electrically stimulate the auditory nerve, to amplify sound, to deliver drugs to the inner ear and potentially for other future applications. The implants require storage space and access to the middle or inner ears. The most acceptable space is the cavity created by a canal wall up mastoidectomy. Detailed knowledge of the available space for implantation and pathways to access the middle and inner ears is necessary for the design of implants and successful implantation. Based on temporal bone CT scans a method for three-dimensional reconstruction of a virtual canal wall up mastoidectomy space is described. Using Amira (R) software the area to be removed during such surgery is marked on axial CT slices, and a three-dimensional model of that space is created. The average volume of 31 reconstructed models is 12.6 cm(3) with standard deviation of 3.69 cm(3), ranging from 7.97 to 23.25 cm(3). Critical distances were measured directly from the model and their averages were calculated: height 3.69 cm, depth 2.43 cm, length above the external auditory canal (EAC) 4.45 cm and length posterior to EAC 3.16 cm. These linear measurements did not correlate well with volume measurements. The shape of the models was variable to a significant extent making the prediction of successful implantation for a given design based on linear and volumetric measurement unreliable. Hence, to assure successful implantation, preoperative assessment should include a virtual fitting of an implant into the intended storage space. The above-mentioned three-dimensional models were exported from Amira to a Solidworks application where virtual fitting was performed. Our results are compared to other temporal bone implant virtual fitting studies. Virtual fitting has been suggested for other human applications. Copyright (C) 2009 S. Karger AG, Basel C1 [McKenna, Michael J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Handzel, Ophir; Wang, Haobing; Murphy, Brian A.; Chen, Zhiqiang; Peppi, Marcello; Sewell, William F.] Harvard Univ, Sch Med, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Handzel, Ophir; Chen, Zhiqiang; Peppi, Marcello; Sewell, William F.; Kujawa, Sharon G.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Sewell, William F.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Fiering, Jason; Borenstein, Jeffrey T.; Mescher, Mark J.; Swan, Erin E. Leary] MIT, Draper Lab, Cambridge, MA 02139 USA. [Swan, Erin E. Leary] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP McKenna, MJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02115 USA. EM michael_mckenna@meei.harvad.edu OI Handzel, Ophir/0000-0002-6905-3034 FU NIH/NIDCD [5R01DC006848]; American Physicians Fellowship FX Supported by NIH/NIDCD grant 5R01DC006848. Ophir Handzel is partially supported by the American Physicians Fellowship program. NR 12 TC 12 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2009 VL 14 IS 5 BP 308 EP 314 DI 10.1159/000212110 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 472DB UT WOS:000268108300006 PM 19372649 ER PT J AU Sewell, WF Borenstein, JT Chen, ZQ Fiering, J Handzel, O Holmboe, M Kim, ES Kujawa, SG McKenna, MJ Mescher, MM Murphy, B Swan, EEL Peppi, M Tao, S AF Sewell, William F. Borenstein, Jeffrey T. Chen, Zhiqiang Fiering, Jason Handzel, Ophir Holmboe, Maria Kim, Ernest S. Kujawa, Sharon G. McKenna, Michael J. Mescher, Mark M. Murphy, Brian Swan, Erin E. Leary Peppi, Marcello Tao, Sarah TI Development of a Microfluidics-Based Intracochlear Drug Delivery Device SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Direct delivery; Drugs; Inner ear; Microfluidics ID GUINEA-PIG; PERILYMPH; RELEASE; CELL AB Background: Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods: We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating innerear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results: We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion: We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases. Copyright (C) 2009 S. Karger AG, Basel C1 [Sewell, William F.; Chen, Zhiqiang; Handzel, Ophir; Kujawa, Sharon G.; McKenna, Michael J.; Murphy, Brian; Peppi, Marcello] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Borenstein, Jeffrey T.; Fiering, Jason; Holmboe, Maria; Kim, Ernest S.; Mescher, Mark M.; Murphy, Brian; Swan, Erin E. Leary; Tao, Sarah] Draper Lab, Cambridge, MA USA. [Swan, Erin E. Leary] MIT, Cambridge, MA 02139 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu OI Handzel, Ophir/0000-0002-6905-3034 FU NIDCD NIH HHS [5R01DC006848-03, R01 DC006848] NR 29 TC 20 Z9 21 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2009 VL 14 IS 6 BP 411 EP 422 DI 10.1159/000241898 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 520CT UT WOS:000271818300008 PM 19923811 ER PT J AU Higginbotham, DJ Beukelman, D Blackstone, S Bryen, D Caves, K Deruyter, F Jakobs, T Light, J McNaughton, D Moulton, B Shane, H Williams, M AF Higginbotham, D. Jeffery Beukelman, David Blackstone, Sarah Bryen, Diane Caves, Kevin Deruyter, Frank Jakobs, Thomas Light, Janice Mcnaughton, David Moulton, Bryan Shane, Howard Williams, Michael B. TI AAC Technology Transfer: An AAC-RERC Report SO AUGMENTATIVE AND ALTERNATIVE COMMUNICATION LA English DT Article DE Augmentative and Alternative Communication (AAC); Technology Transfer; Knowledge Transfer ID PERFORMANCE; PROTOTYPE AB Transferring innovative technologies from the university to the manufacturing sector can often be an elusive and problematic process. The Rehabilitation and Engineering Research Center on Communication Enhancement (AAC-RERC) has worked with the manufacturing community for the last 10 years. The purpose of this article is to discuss barriers to technology transfer, to outline some technology transfer strategies, and to illustrate these strategies with AAC-RERC related activities. C1 [Bryen, Diane] Temple Univ, Philadelphia, PA 19122 USA. [Higginbotham, D. Jeffery] SUNY Buffalo, Dept Communicat Disorders & Sci, Ctr Excellence Augmented Commun, Buffalo, NY 14216 USA. [Beukelman, David] Univ Nebraska, Lincoln, NE 68583 USA. [Caves, Kevin; Deruyter, Frank] Duke Univ, Durham, NC 27706 USA. [Light, Janice; Mcnaughton, David] Penn State Univ, University Pk, PA 16802 USA. [Shane, Howard] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Higginbotham, DJ (reprint author), SUNY Buffalo, Dept Communicat Disorders & Sci, Ctr Excellence Augmented Commun, 122 Cary Hall, Buffalo, NY 14216 USA. EM cdsjeff@buffalo.edu RI McNaughton, David/G-4822-2010 NR 18 TC 2 Z9 2 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0743-4618 J9 AUGMENT ALTERN COMM JI Augment. Altern. Commun. PY 2009 VL 25 IS 1 BP 68 EP 76 AR PII 909395931 DI 10.1080/07434610902724886 PG 9 WC Audiology & Speech-Language Pathology; Rehabilitation SC Audiology & Speech-Language Pathology; Rehabilitation GA 417RZ UT WOS:000264096400008 PM 19280423 ER PT J AU Nierenberg, AA Trivedi, MH Gaynes, BN Mitchell, J Davis, LL Husain, MM Wisniewski, SR Fava, M Warden, D Luther, JF van Nieuwenhuizen, AO Morris, DW Shelton, RC Rush, AJ AF Nierenberg, Andrew A. Trivedi, Madhukar H. Gaynes, Bradley N. Mitchell, Jeff Davis, Lori L. Husain, Mustafa M. Wisniewski, Stephen R. Fava, Maurizio Warden, Diane Luther, James F. van Nieuwenhuizen, Adrienne O. Morris, David W. Shelton, Richard C. Rush, A. John TI Effectiveness study of venlafaxine-XR combined with aripiprazole for chronic or recurrent major depressive disorder SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE Aripiprazole; major depressive disorder; venlafazine-XR ID SEROTONIN REUPTAKE INHIBITORS; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; MEDICATION ALGORITHM PROJECT; STAR-ASTERISK-D; REPORT QIDS-SR; DOUBLE-BLIND; CONTROLLED-TRIAL; QUICK INVENTORY; RATING-SCALE; ANTIPSYCHOTIC ARIPIPRAZOLE AB Objective: Although the second-generation antipsychotic, aripiprazole (ARI), has been approved as an adjunct for treatment-resistant major depressive disorder (MDD), neither ARI nor any second-generation antipsychotic has been assessed in combination with an antidepressant at the initiation of a treatment trial for non-treatment-resistant MDD. The aim of the present study was therefore to assess the safety, tolerability, and remission rate in the treatment of MDD using the specific combination of venlafaxine-XR (VEN-XR) and ARI in a generalizable, difficult-to-treat group with chronic or recurrent MDD. Methods: Self-declared participants in primary care or psychiatric settings who had chronic or recurrent MDD and a minimum score of 14 on the 17-item Hamilton Rating Scale for Depression were included. Up to 12 weeks of open treatment with the combination of VEN-XR and ARI was provided. Participants began with VEN-XR, and ARI was added at week 2. Maximum allowable doses were 300 mg day (1) for venlafaxine-XR and 30 mg day (1) for ARI. Remission was defined as <= 5 on the 16-item Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR(16)). Results: Fifty outpatients with non-psychotic MDD were enrolled ( mean age = 439 +/- 11 years; 38% male; QIDS-SR(16) = 15 +/- 3). Mean exit dose of VEN-XR was 227 +/- 97 mg day (1), and the mean exit dose of ARI was 11 +/- 7 mg day (1). The combination was well tolerated; 16% of participants discontinued due to side-effects. Approximately 70% achieved remission at some point during the trial, and 66% achieved remission at study exit. Conclusions: To the best of the authors' knowledge this is the first study to combine an antidepressant and second-generation antipsychotic at the beginning of a treatment trial for chronic or recurrent non-treatment resistant MDD. VEN-XR and ARI combination appears to warrant further study in controlled trials. C1 [Nierenberg, Andrew A.; Fava, Maurizio; van Nieuwenhuizen, Adrienne O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. [Trivedi, Madhukar H.; Husain, Mustafa M.; Warden, Diane; Morris, David W.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Gaynes, Bradley N.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Mitchell, Jeff] Univ Oklahoma, Coll Med, Tulsa, OK USA. [Mitchell, Jeff] Laureate Psychiat Clin & Hosp, Tulsa, OK USA. [Davis, Lori L.] Univ Alabama, Sch Med, Tuscaloosa, AL 35487 USA. [Davis, Lori L.] VA Med Ctr, Tuscaloosa, AL USA. [Wisniewski, Stephen R.; Luther, James F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Shelton, Richard C.] Vanderbilt Univ, Nashville, TN USA. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. EM anierenberg@partners.org OI Gaynes, Bradley/0000-0002-8283-5030; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU Robert Wood Johnson Foundation; National Institute of Mental Health; Stanley Foundation; Forest Pharmaceuticals; GlaxoSmithKline; Eli Lilly; Pfizer FX In the past 3 years, Dr Nierenberg consulted to and served on advisory boards of Abbott Laboratories, Appliance Computing, Brain Cells, Bristol Myers Squibb, EpiQ, Pam Labs, PGX Health, Forest Pharmaceuticals, Eli Lilly & Co, GlaxoSmithKline, Janssen, Pharmaceutica, Jazz Pharmaceuticals, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Schering-Plough, Sepracor, Shire, Somerset, Takeda, and Targacept. He has received research support from Cyberonics, Cederroth, Ortho-McNeil-Janssen, Pfizer, Pam Labs and Shire. He received honoraria from the MGH Psychiatry Academy (MGHPA are supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: Astra Zeneca, Eli Lilly, and Janssen Pharmaceuticals). Dr Nierenberg owns stock options in Appliance Computing. Dr Rush has provided scientific consultation to or served on Advisory Boards for Advanced Neuromodulation Systems; AstraZeneca; Best Practice Project Management; Bristol-Myers Squibb Company; Cyberonics; Forest Pharmaceuticals; Gerson Lehman Group; GlaxoSmithKline; Jazz Pharmaceuticals; Eli Lilly Magellan Health Services; Merck Neuronetics; Ono Pharmaceutical; Organon USA; PamLab, Personality Disorder Research Corp.; Pfizer; The Urban Institute; and Wyeth-Ayerst Laboratories. He has received royalties from Guilford Publications and Healthcare Technology Systems, and research/grant support from the Robert Wood Johnson Foundation, the National Institute of Mental Health, and the Stanley Foundation; has been on speaker bureaus for Cyberonics, Forest Pharmaceuticals, GlaxoSmithKline, and Eli Lilly and owns stock in Pfizer. NR 48 TC 6 Z9 6 U1 1 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PY 2009 VL 43 IS 10 BP 956 EP 967 DI 10.1080/00048670903001885 PG 12 WC Psychiatry SC Psychiatry GA 514PC UT WOS:000271406200009 ER PT J AU Byrne, FR Winters, A Brankow, D Hu, S Juan, T Steavenson, S Doellgast, G Kuchimanchi, K Brown, H Anderson, S Smelt, S Sullivan, T Alcorn, D Tocker, J Dean, C Macmaster, J Kirchner, J Buys, J Manoukian, R Jiao, E Zou, XM Campanella, G Siu, G AF Byrne, Fergus R. Winters, Aaron Brankow, David Hu, Sylvia Juan, Todd Steavenson, Shirley Doellgast, George Kuchimanchi, Kamesh Brown, Heather Anderson, Sharon Smelt, Sara Sullivan, Tim Alcorn, Dina Tocker, Joel Dean, Charley, Jr. Macmaster, John Kirchner, Jacqueline Buys, Janet Manoukian, Raffi Jiao, Eric Zou, Xiaoming Campanella, Gabriele S. Siu, Gerald TI An antibody to IP-10 is a potent antagonist of cell migration in vitro and in vivo and does not affect disease in several animal models of inflammation SO AUTOIMMUNITY LA English DT Article DE Inflammation; mouse; chemokine; IP-10; monoclonal antibody ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHEMOKINE RECEPTOR CXCR3; ACUTE ALLOGRAFT-REJECTION; IFN-INDUCIBLE PROTEIN-10; MULTIPLE-SCLEROSIS; INTERFERON-GAMMA; T-CELLS; AIRWAY HYPERREACTIVITY; RHEUMATOID-ARTHRITIS; LIGAND IP-10 AB IP-10 secretion is induced by pro-inflammatory cytokines and mediates the migration of CXCR3+ cells. Its elevation in clinical samples has been associated with multiple inflammatory diseases and its antagonism has been reported to be effective in several animal models of inflammatory disease. We generated a mouse anti-mouse IP-10 monoclonal antibody (mAb; Clone 20A9) that specifically bound murine IP-10 with high affinity and inhibited in vitro IP-10 induced BaF3/mCXCR3 cell migration with an IC50 of 4nM. The 20A9 mAb was completely absorbed in vivo and had dose proportional pharmacokinetic exposure with a serum half life of 2.4-6 days. The 20A9 mAb inhibited IP-10 mediated T-cell recruitment to the airways, indicating that it is effective in vivo. However, administration of the 20A9 mAb had no significant effect on disease in mouse models of delayed type hypersensitivity, collagen induced arthritis, cardiac allograft transplantation tolerance, EAE or CD4+ CD45RBHi T-cell transfer-induced IBD. These data suggest that the 20A9 mAb can antagonize IP-10 mediated chemotaxis in vitro and in vivo and that this is insufficient to cause a therapeutic benefit in multiple mouse models of inflammatory disease. C1 [Byrne, Fergus R.] Amgen Inc, Dept Inflammat Res, Thousand Oaks, CA 91320 USA. [Sullivan, Tim] Amgen Inc, San Francisco, CA USA. [Alcorn, Dina; Tocker, Joel; Dean, Charley, Jr.; Macmaster, John; Kirchner, Jacqueline] Amgen Inc, Seattle, WA USA. [Campanella, Gabriele S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Byrne, FR (reprint author), Amgen Inc, Dept Inflammat Res, Mail Stop 29-1-B, Thousand Oaks, CA 91320 USA. EM fbyrne@amgen.com NR 48 TC 17 Z9 17 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 PY 2009 VL 42 IS 3 BP 171 EP 182 AR PII 909714577 DI 10.1080/08916930802629547 PG 12 WC Immunology SC Immunology GA 421FY UT WOS:000264346000001 PM 19301198 ER PT J AU Huett, A McCarroll, SA Daly, MJ Xavier, RJ AF Huett, Alan McCarroll, Steven A. Daly, Mark J. Xavier, Ramnik J. TI On the level IRGM gene function is all about expression SO AUTOPHAGY LA English DT Article DE Crohn disease; inflammation; infection; bacteria; host-pathogen interaction; innate immunity ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; AUTOPHAGY; PATHOGENESIS; SCAN; SNPS AB Crohn disease is a complex, multigenic, chronic inflammatory bowel disease of uncertain etiology. Recent advances in genetics, including high-throughput single-nucleotide polymorphism typing platforms and deep sequencing technologies have begun to shed light upon disease predisposition and pathogenesis. Autophagy is emerging as a key player in both innate and adaptive immunity, as well as tissue homeostasis and development in the gut. Here we describe our recent studies into the Crohn disease-associated Immunity-Related GTPase family, M (IRGM) gene and our discovery of a large risk-conferring upstream deletion. We discuss the effects of this deletion upon expression levels of IRGM alleles and how tissue-specific expression might be affected by the promoter polymorphism. In addition, we comment upon the potential roles of IRGM in autophagy of intracellular pathogens, and the challenges ahead for further elucidating IRGM function. C1 [Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Cambridge, MA 02114 USA. [Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Cambridge, MA 02114 USA. [McCarroll, Steven A.; Daly, Mark J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA 02114 USA. [McCarroll, Steven A.; Daly, Mark J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Cambridge, MA 02114 USA. [McCarroll, Steven A.; Daly, Mark J.] MIT & Harvard, Broad Inst, Cambridge, MA USA. RP Xavier, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Cambridge, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu FU NIDDK NIH HHS [P30 DK040561-13, P30 DK040561] NR 19 TC 5 Z9 5 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JAN PY 2009 VL 5 IS 1 BP 96 EP 99 PG 4 WC Cell Biology SC Cell Biology GA 400CE UT WOS:000262844800014 PM 19029815 ER PT J AU Dickerson, BC Sperling, RA AF Dickerson, Bradford C. Sperling, Reisa A. TI Large-scale functional brain network abnormalities in Alzheimer's disease: Insights from functional neuroimaging SO BEHAVIOURAL NEUROLOGY LA English DT Review DE Alzheimer's disease; mild cognitive impairment; functional magnetic resonance imaging; hippocampus; parietal cortex ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; APOLIPOPROTEIN-E EPSILON-4; HIPPOCAMPAL ACTIVATION; GENETIC RISK; OLDER-ADULTS; DEFAULT-MODE; PARIETAL DEACTIVATION; RECOGNITION MEMORY; SUBSEQUENT MEMORY AB Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have begun to reveal abnormalities in large-scale memory and cognitive brain networks. Since the medial temporal lobe (MTL) memory system is a site of very early pathology in AD, a number of studies have focused on this region of the brain. Yet it is clear that other regions of the large-scale episodic memory network are affected early in the disease as well, and fMRI has begun to illuminate functional abnormalities in frontal, temporal, and parietal cortices as well in MCI and AD. Besides predictable hypoactivation of brain regions as they accrue pathology and undergo atrophy, there are also areas of hyperactivation in brain memory and cognitive circuits, possibly representing attempted compensatory activity. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. Additional work with "resting state" fMRI data is illuminating functional-anatomic brain circuits and their disruption by disease. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, which will hopefully one day be useful for demonstrating beneficial effects of treatments being tested in clinical trials. C1 [Dickerson, Bradford C.; Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Dickerson, Bradford C.; Sperling, Reisa A.] Harvard Univ, Sch Med, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02115 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Frontotemporal Dementia Unit, Boston, MA 02115 USA. [Dickerson, Bradford C.; Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Dickerson, Bradford C.; Sperling, Reisa A.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU NIA [R21-AG029840, R01-AG029411, R01-AG027435, P50-AG05134]; Alzheimer's Association FX The authors would like to thank our patients, coland study staff for continued inspiration. Supported, by grants from the NIA (R21-AG029840, R01-AG029411, R01-AG027435, P50-AG05134) and the Alzheimer's Association. NR 109 TC 97 Z9 98 U1 5 U2 20 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2009 VL 21 IS 1-2 BP 63 EP 75 DI 10.3233/BEN-2009-0227 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 525FZ UT WOS:000272201300008 PM 19847046 ER PT J AU Pihlajamaki, M Sperling, RA AF Pihlajamaki, Maija Sperling, Reisa A. TI Functional MRI assessment of task-induced deactivation of the default mode network in Alzheimer's disease and at-risk older individuals SO BEHAVIOURAL NEUROLOGY LA English DT Article DE Aging; Alzheimer's disease (AD); apolipoprotein E; default mode network; functional magnetic resonance imaging (fMRI); memory; mild cognitive impairment (MCI); posterior cingulate cortex; precuneus; task-induced deactivation ID MILD COGNITIVE IMPAIRMENT; RESTING-STATE NETWORKS; ENTORHINAL CORTEX NEURONS; VOXEL-BASED MORPHOMETRY; APOLIPOPROTEIN-E; POSTERIOR CINGULATE; HIPPOCAMPAL ACTIVATION; BASE-LINE; PARIETAL DEACTIVATION; CORTICAL AFFERENTS AB Alzheimer's disease (AD) is the most common form of dementia in old age, and is characterized by prominent impairment of episodic memory. Recent functional imaging studies in AD have demonstrated alterations in a distributed network of brain regions supporting memory function, including regions of the default mode network. Previous positron emission tomography studies of older individuals at risk for AD have revealed hypometabolism of association cortical regions similar to the metabolic abnormalities seen in AD patients. In recent functional magnetic resonance imaging (fMRI) studies of AD, corresponding brain default mode regions have also been found to demonstrate an abnormal fMRI task-induced deactivation response pattern. That is, the relative decreases in fMRI signal normally observed in the default mode regions in healthy subjects performing a cognitive task are not seen in AD patients, or may even be reversed to a paradoxical activation response. Our recent studies have revealed alterations in the pattern of deactivation also in elderly individuals at risk for AD by virtue of their APOE e4 genotype, or evidence of mild cognitive impairment (MCI). In agreement with recent reports from other groups, these studies demonstrate that the pattern of fMRI task-induced deactivation is progressively disrupted along the continuum from normal aging to MCI and to clinical AD and more impaired in e4 carriers compared to non-carriers. These findings will be discussed in the context of current literature regarding functional imaging of the default network in AD and at-risk populations. C1 [Pihlajamaki, Maija] Univ Kuopio, Neurol Unit, Inst Clin Med, FIN-70211 Kuopio, Finland. [Pihlajamaki, Maija; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Memory Disorders Unit, Sch Med,Dept Neurol, Boston, MA 02115 USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pihlajamaki, M (reprint author), Univ Kuopio, Neurol Unit, Inst Clin Med, POB 1627, FIN-70211 Kuopio, Finland. EM Maija.Pihlajamaki@uku.fi FU Academy of Finland [108188, 214050]; NINDS [K23-NS02189]; NIA [R01 AG027435, PO1-AG04953, P50-AG00513421] FX This study was supported by Academy of Finland grants #108188 and #214050 as well as the following grants: NINDS K23-NS02189, NIA R01 AG027435, NIA PO1-AG04953, and NIA P50-AG00513421. We thank the staff of the Massachusetts General Hospital Gerontology Research Unit and Brigham and Women's Hospital Memory Disorders Unit Clinical Research for assistance with subject recruitment, evaluation, and data management, as well as Mary Foley, Larry White, and the Athinoula A. Martinos Center staff for assistance with MRI data collection. We express special gratitude to the subjects who participated in this study. NR 96 TC 54 Z9 55 U1 1 U2 19 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2009 VL 21 IS 1-2 BP 77 EP 91 DI 10.3233/BEN-2009-0231 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 525FZ UT WOS:000272201300009 PM 19847047 ER PT J AU Drzezga, A AF Drzezga, Alexander TI Diagnosis of Alzheimer's disease with [18F]PET in mild and asymptomatic stages SO BEHAVIOURAL NEUROLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; TEMPORAL-LOBE ATROPHY; POSTERIOR CINGULATE CORTEX; QUALITY STANDARDS SUBCOMMITTEE; ACADEMY-OF-NEUROLOGY; COGNITIVE IMPAIRMENT; FDG-PET; F-18-FDG PET; APOLIPOPROTEIN-E AB With longer life expectancy, dementia based on the age-related Alzheimers' disease (AD) has turned into one of the most prevalent disorders of older age, representing a serious medical and socio-economic issue. There has been growing interest in early diagnosis of this disease, particularly regarding the initiation of new treatment strategies ahead of the onset of irreversible neuronal damage. It is accepted that the pathologic changes underlying AD appear in the brain years to decades before the symptomatic stages. Consequently, clinical measures of cognitive impairment, as used for definition of dementia, will not allow early diagnosis of AD-pathology in the mild or asymptomatic stages. Thus, a need for complementary sensitive biomarkers is apparent. Brain imaging markers are among the most promising candidates for this diagnostic challenge. Particularly, [18F]FDG PET as a marker of regional neuronal function has been demonstrated to represent a most sensitive and specific method for early identification of AD-pathology and thus for prediction of dementia of the Alzheimer type (DAT), even in the mild and asymptomatic stages. Currently, systematic data of comparable quality are hardly available for any other imaging procedure. The purpose of this article is to describe the typical findings of [18F]FDG PET in different stages of AD and to demonstrate its value for early and reliable diagnosis of Alzheimer's disease, particularly ahead of the stage of dementia of the Alzheimer's type. C1 [Drzezga, Alexander] Tech Univ Munich, Nukl Med Klin, Klinikum Rechts Isar, Dept Nucl Med, D-81675 Munich, Germany. [Drzezga, Alexander] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA. RP Drzezga, A (reprint author), Tech Univ Munich, Nukl Med Klin, Klinikum Rechts Isar, Dept Nucl Med, Ismaninger Str 22, D-81675 Munich, Germany. EM a.drzezga@lrz.tu-muenchen.de FU Deutsche Forschungsgemeinschaft [DR 445/3-1, DR 445/4-1] FX This work has been supported in part by DFG-grants (Deutsche Forschungsgemeinschaft) Project Numbers: DR 445/3-1, DR 445/4-1 (Drzezga). The author thanks Nicola Karina for the careful review of the manuscript. NR 119 TC 18 Z9 18 U1 3 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2009 VL 21 IS 1-2 BP 101 EP 115 DI 10.3233/BEN-2009-0228 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 525FZ UT WOS:000272201300011 PM 19847049 ER PT J AU Fishman, JA AF Fishman, Jay A. BE Savage, GT Fottler, MD TI MATRIX MENTORSHIP IN ACADEMIC MEDICINE: SUSTAINABILITY OF COMPETITIVE ADVANTAGE SO BIENNIAL REVIEW OF HEALTH CARE MANAGEMENT: MESO PERSPECTIVE SE Advances in Health Care Management LA English DT Article; Book Chapter ID PROFESSIONAL-DEVELOPMENT; FACULTY-DEVELOPMENT; EFFORTS FAIL; ROLE MODELS; PROGRAM; RESIDENCY; EDUCATION; BENEFITS; LESSONS; NETWORK AB The health care system is undergoing rapid change as medical centers are confronted with constricted reimbursements for healthcare services while adapting to growth in medical knowledge, major technological advances in medical practice, and a changing regulatory environment. Academic medical centers thought themselves immune to the forces that shape most service enterprises but are forced to compete based on customer service and the efficiency, quality, and safety of medical care, while continuing to compete in the academic world. These challenges are not unique to academic medicine, but these institutions are, perhaps, least suited to the leadership challenges posed by this environment. Certain attributes of these centers raise barriers to successful adaptation to the changing healthcare environment. The need for systemic change in academic medicine requires commitment to programs that create change agents willing to assume leadership roles and to guide institutional evolution. In academic medicine, traditional one-on-one relationships between mentors and trainees do not provide the breadth of guidance needed in the complex environment of research, medical practice, and teaching. A structured system of "matrix mentorship" and structured evaluation will advance institutional values, provide leaders with an essential set of skills and values consistent with institutional goals, and provide competitive advantage for medical centers in academic healthcare. C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Fishman, Jay A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Sch Med, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 64 TC 1 Z9 1 U1 0 U2 1 PU EMERALD GROUP PUBLISHING LIMITED PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY, W YORKSHIRE BD16 1WA, ENGLAND BN 978-1-84855-672-0 J9 ADV HEALTH CARE MANA PY 2009 VL 8 BP 155 EP 170 DI 10.1108/S1474-8231(2009)0000008010 PG 16 WC Health Policy & Services SC Health Care Sciences & Services GA BLS25 UT WOS:000270924000007 ER PT J AU Mujagic, Z Srabovic, N Mujagic, H AF Mujagic, Zlata Srabovic, Nahida Mujagic, Hamza TI The role of prolactin in human breast cancer SO BIOCHEMIA MEDICA LA English DT Review DE prolactin; breast cancer; prolactin receptors; prolactin signaling pathways; hyperprolactinemia ID MAMMARY EPITHELIAL-CELLS; CAPILLARY ENDOTHELIAL-CELLS; POLYMERASE-CHAIN-REACTION; GROWTH-HORMONE RECEPTOR; SIGNAL-TRANSDUCTION; PLASMA PROLACTIN; PREMENOPAUSAL WOMEN; BINDING-SITE; PRL RECEPTOR; STIMULATED PROLIFERATION AB Much of the literature on human breast cancer and prolactin (PRL)appears to be contradictory. PRL has been first recognized as a hormone that plays an important role in breast cancer initiation and development in rodents, and, at least partly, in humans. Bioactive PRL is synthesized by human breast cancer cells in culture and acts in an autocrine/paracrine stimulatory loop within breast tissue. The actions of this ligand are mediated by PRL receptor (PRLR) isoforms found on, or secreted by, human breast epithelium. The PRL/PRLR complex associates with, and activates, several signaling pathways that are shared with other members of the cytokine receptor superfamily. Proximal PRLR signaling is initiated by three tyrosine kinases, namely Jak2, Src, and Tec. Some recent literature data have indicated a functional role for PRL within the nucleus where it acts in a complex with cyclophilin B as a transcriptional inducer. Several epidemiological studies have indicated that PRL may also function as a progression fact or for human breast cancer. PRL might be an important local growth promoter involved in the pathogenesis of human breast cancer. Hyperprolactinemia could be an indicator of disease progression and poor prognosis and clinical approaches to controlling this disease need to incorporate antagonists of PRL/PRLR interaction or PRL receptor-associated signal transduction. C1 [Mujagic, Zlata; Srabovic, Nahida] Univ Tuzla, Fac Pharm, Dept Biochem, Tuzla 75000, Bosnia & Herceg. [Mujagic, Hamza] Harvard Univ, Boston, MA 02115 USA. [Mujagic, Hamza] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mujagic, Z (reprint author), Univ Tuzla, Fac Pharm, Dept Biochem, Univ Ska 1, Tuzla 75000, Bosnia & Herceg. EM zlata.mujagic@gmail.com NR 125 TC 2 Z9 3 U1 0 U2 2 PU CROATIAN SOC MEDICAL BIOCHEMISTS PI ZAGREB PA DOMAGOJEVA 2, ZAGREB, 10000, CROATIA SN 1330-0962 EI 1846-7482 J9 BIOCHEM MEDICA JI Biochem. Medica. PY 2009 VL 19 IS 3 BP 236 EP 249 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 505CV UT WOS:000270667000003 ER PT J AU Feng, SM Deng, LF Chen, W Shao, JZ Xu, GL Li, YP AF Feng, Shengmei Deng, Lianfu Chen, Wei Shao, Jianzhong Xu, Guoliang Li, Yi-Ping TI Atp6v1c1 is an essential component of the osteoclast proton pump and in F-actin ring formation in osteoclasts SO BIOCHEMICAL JOURNAL LA English DT Article DE acidification; Atp6v1c1 (C1); bone resorption; filamentous actin (F-actin) ring; osteoclast; vacuolar-type proton-translocating ATPase (V-ATPase) ID VACUOLAR H+-ATPASE; MEDIATED EXTRACELLULAR ACIDIFICATION; V-ATPASE; SUBUNIT ISOFORMS; BONE-RESORPTION; C-SUBUNIT; RESORBING OSTEOCLASTS; PLASMA-MEMBRANE; CROSS-LINKING; A3 ISOFORM AB Bone resorption relies oil the extracellular acidification function of V-ATPase (vacuolar-type proton-translocating ATPase) proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of the osteoclast-specific ruffled border V-ATPases remains largely unknown. In the present study, we found that the V-ATPase Subunit Atp6v1c1 (C1) is highly expressed in osteoclasts, whereas Subunits Atp6v1c2a (C2a) and Atp6v1c2b (C2b) are not. The expression level of C I is highly induced by RANKL [receptor activator for NF-kappa B (nuclear factor kappa B) ligand] during osteoclast differentiation; C1 interacts with Atp6v0a3 (a3) and is mainly localized on the ruffled border of activated osteoclasts. The results of the present study show for the first time that C1-silencing by lentivirus-mediated RNA interference severely impaired osteoclast acidification activity and bone resorption, whereas cell differentiation did not appear to be affected, which is similar to a3 silencing. The F-actin (filamentous actin) ring formation was severely defected in C1-depleted osteoclasts but not in a3-depleted and a3(-/-) osteoclasts. C1 co-localized with microtubules in the plasma membrane and its vicinity in mature osteoclasts. In addition, C1 co-localized with F-actin in the cytoplasm; however, the co-localization chiefly shifted to the cell periphery of Mature osteoclasts. The present study demonstrates that Atp6v1c1 is all essential component of the osteoclast proton pump at the osteoclast ruffled border and that it may regulate F-actin ring formation in osteoclast activation. C1 [Feng, Shengmei; Shao, Jianzhong; Li, Yi-Ping] Zhejiang Univ, Life Sci Coll, Hangzhou 310058, Peoples R China. [Feng, Shengmei; Chen, Wei; Li, Yi-Ping] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Deng, Lianfu; Li, Yi-Ping] Shanghai Inst Traumatol & Orthopaed, Shanghai 200025, Peoples R China. [Chen, Wei; Li, Yi-Ping] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Xu, Guoliang] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. [Li, Yi-Ping] Zhejiang Cell Biomed Res Coll, Hangzhou 310006, Zhejiang, Peoples R China. RP Li, YP (reprint author), Zhejiang Univ, Life Sci Coll, 388 Yuhang Rd, Hangzhou 310058, Peoples R China. EM ypli@forsyth.org FU Zhejiang Cell Biomedical Research College, CSC (China Scholarship Council); NIH (National Institutes of Health) [AR-44741] FX We thank Christie Taylor and Carrie Soltanoff for their assistance with the manuscript before submission. This work was supported by the fund provided by Zhejiang Cell Biomedical Research College, CSC (China Scholarship Council) and NIH (National Institutes of Health) Grant AR-44741 (to Y.-P.L.). NR 42 TC 38 Z9 40 U1 3 U2 10 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2009 VL 417 BP 195 EP 203 DI 10.1042/BJ20081073 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 391JX UT WOS:000262230700019 PM 18657050 ER PT J AU Joshi, AS Zhou, JM Gohil, VM Chen, SL Greenberg, ML AF Joshi, Amit S. Zhou, Jingming Gohil, Vishal M. Chen, Shuliang Greenberg, Miriam L. TI Cellular functions of cardiolipin in yeast SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Cardiolipin; Barth syndrome; Protein import; Aging; Mitochondrial bioenergetics and biogenesi; Cell wall ID SUPPRESSES TEMPERATURE SENSITIVITY; RESPIRATORY-CHAIN SUPERCOMPLEXES; LINKED CARDIOSKELETAL MYOPATHY; INNER MITOCHONDRIAL-MEMBRANE; ELECTRON-TRANSPORT CHAIN; BEEF-HEART MITOCHONDRIA; CYTOCHROME-C RELEASE; BARTH-SYNDROME; SACCHAROMYCES-CEREVISIAE; OXIDATIVE-STRESS AB Cardiolipin (CL), the signature lipid of mitochondria, plays a critical role in mitochondrial function and biogenesis. The availability of yeast mutants blocked in CL synthesis has facilitated studies of the biological role of this lipid. Perturbation of CL synthesis leads to growth defects not only during respiratory growth but also under conditions in which respiration is not essential. CL was shown to play a role in mitochondrial protein import, cell wall biogenesis, aging and apoptosis, ceramide synthesis, and translation of electron transport chain components. The genetic disorder Barth syndrome (BTHS) is caused by mutations in the tafazzin gene resulting in decreased total CL levels, accumulation of monolysocardiolipin (MLCL), and decreased unsaturated fatty acyl species of CL The variation in clinical presentation of BTHS indicates that other physiological factors play a significant role in modifying the phenotype resulting from tafazzin deficiency. Elucidating the functions of CL is expected to shed light on the role of this important lipid in BTHS and other disorders of mitochondrial dysfunction. (C) 2008 Elsevier B.V. All rights reserved. C1 [Joshi, Amit S.; Zhou, Jingming; Chen, Shuliang; Greenberg, Miriam L.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Gohil, Vishal M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Gohil, Vishal M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. RP Greenberg, ML (reprint author), Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. EM MLGREEN@sun.science.wayne.edu RI Chen, Shuliang/N-9498-2013 OI Chen, Shuliang/0000-0002-7175-7604 FU National Institutes of Health [HL 62263, HL084218]; Barth Syndrome Foundation FX The authors acknowledge support from the National Institutes of Health (Grants HL 62263 and HL084218) and The Barth Syndrome Foundation. NR 113 TC 80 Z9 80 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN PY 2009 VL 1793 IS 1 BP 212 EP 218 DI 10.1016/j.bbamcr.2008.07.024 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 398NH UT WOS:000262738300024 PM 18725250 ER PT J AU Garanger, E Weissleder, R Josephson, L AF Garanger, Elisabeth Weissleder, Ralph Josephson, Lee TI A Multifunctional Single-Attachment-Point Reagent for Controlled Protein Biotinylation SO BIOCONJUGATE CHEMISTRY LA English DT Article AB The biotin/avidin system is one of the most widely used affinity detection and affinity capture systems in biology. However, the determination of the exact number of biotin tags attached onto a substrate is complicated by the fact that biotin does not present any light-absorbing or -emitting properties. Here, we describe a fluorescent biotinylation reagent designed from the general multifunctional single-attachment-point (MSAP) reagent concept. A Lys-Cys dipeptide scaffold was used to display a biotin functional group and a fluorescein functional group along with an N-hydroxysuccinimide ester reactive group. The resulting bifunctional MSAP reagent, Fl-Biotin-NHS, was used to prepare a monobiotinylated version of cetuximab, which was further reacted with avidin to obtain a soluble avidin-based cetuximab oligomer. The MSAP peptide-scaffold approach allows fluorophores, chromophores, or reactive groups to be combined with biotin and provides a broad approach to obtain multifunctional biotin-based reagents. C1 [Garanger, Elisabeth; Weissleder, Ralph; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. [Garanger, Elisabeth; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Boston, MA 02129 USA. EM ljosephson@mgh.harvard.edu FU [R01 EB004472]; [R01 EB00662]; [P50 CA86355] FX This work was supported by R01 EB004472, R01 EB00662 and P50 CA86355. NR 3 TC 6 Z9 6 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2009 VL 20 IS 1 BP 170 EP 173 DI 10.1021/bc800392t PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 397JT UT WOS:000262659700022 PM 19072220 ER PT J AU Ferreira, MAR Purcell, SM AF Ferreira, Manuel A. R. Purcell, Shaun M. TI A multivariate test of association SO BIOINFORMATICS LA English DT Article ID QUANTITATIVE TRAITS; LINKAGE ANALYSES; POWER AB Although genetic association studies often test multiple, related phenotypes, few formal multivariate tests of association are available. We describe a test of association that can be efficiently applied to large population-based designs. C1 [Ferreira, Manuel A. R.; Purcell, Shaun M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ferreira, Manuel A. R.; Purcell, Shaun M.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Ferreira, Manuel A. R.; Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ferreira, Manuel A. R.; Purcell, Shaun M.] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Ferreira, Manuel A. R.; Purcell, Shaun M.] MIT, Cambridge, MA 02139 USA. [Ferreira, Manuel A. R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Purcell, Shaun M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Ferreira, MAR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI Ferreira, Manuel/D-3609-2013 FU National Health and Medical Research Council of Australia FX Sidney Sax Fellowship from the National Health and Medical Research Council of Australia (to M. A. R. F.). NR 7 TC 95 Z9 97 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2009 VL 25 IS 1 BP 132 EP 133 DI 10.1093/bioinformatics/btn563 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 388BX UT WOS:000261996400024 PM 19019849 ER PT B AU Chervitz, SA Parkinson, H Fostel, JM Causton, HC Sanson, SA Deutsch, EW Field, D Taylor, CF Rocca-Serra, P White, J Stoeckert, CJ AF Chervitz, Stephen A. Parkinson, Helen Fostel, Jennifer M. Causton, Helen C. Sanson, Susanna-Assunta Deutsch, Eric W. Field, Dawn Taylor, Chris F. Rocca-Serra, Philippe White, Joe Stoeckert, Christian J. BE Edwards, D Stajich, J Hansen, D TI Standards for Functional Genomics SO BIOINFORMATICS: TOOLS AND APPLICATIONS LA English DT Article; Book Chapter ID MINIMUM REPORTING STANDARDS; MICROARRAY DATA; GENE-EXPRESSION; PLANT METABOLOMICS; MASS-SPECTROMETRY; WORKING GROUP; DATA EXCHANGE; DATA FORMAT; MAGE-TAB; INFORMATION C1 [Chervitz, Stephen A.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Parkinson, Helen; Sanson, Susanna-Assunta; Taylor, Chris F.; Rocca-Serra, Philippe] European Bioinformat Inst, Cambridge, England. [Fostel, Jennifer M.] Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC 27709 USA. [Causton, Helen C.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England. [Deutsch, Eric W.] Inst Syst Biol, Seattle, WA 98105 USA. [Field, Dawn] Ctr Ecol & Hydrol, Nat Environm Res Council, Oxford OX1 3SR, England. [White, Joe] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Joe] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Stoeckert, Christian J.] Univ Penn, Sch Med, Dept Genet, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA. RP Chervitz, SA (reprint author), Affymetrix Inc, Santa Clara, CA 95051 USA. EM Steve_Chervitz@affymetrix.com; parkinson@ebi.ac.uk; fostel@niehs.nih.gov; helen.causton@csc.mrc.ac.uk; sansone@ebi.ac.uk; edeutsch@systemsbiology.org; dfield@cch.ac.uk; christ@ebi.ac.uk; rocca@ebi.ac.uk; jwhite@jimmy.harvard.edu; stoeckrt@pcbi.upenn.edu OI Taylor, Ronald/0000-0001-9777-9767 NR 73 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-92737-4 PY 2009 BP 293 EP 329 DI 10.1007/978-0-387-92738-1_15 D2 10.1007/978-0-387-92738-1 PG 37 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology GA BMH82 UT WOS:000272399500015 ER PT S AU Harris, E McNamara, P AF Harris, Erica McNamara, Patrick BE Voland, E Schiefenhovel, W TI Neurologic Constraints on Evolutionary Theories of Religion SO BIOLOGICAL EVOLUTION OF RELIGIOUS MIND AND BEHAVIOR SE Frontiers Collection LA English DT Article; Book Chapter ID PARKINSONS-DISEASE; PHYSICAL HEALTH; SPIRITUALITY; TEMPERAMENT; CHARACTER; EPILEPSY AB Patients with Parkinson's disease (PD) experience a selective depletion of neostriatal and meso-frontal dopamine and thus provide an ideal model for assessing potential dopaminergic influences on religious cognition and experience. We review three specific studies conducted in our laboratory focusing on reports of various facets of religiousness in patients with PD. We find that (1) there is a reduction in self-reported religiousness among these patients as compared to healthy age-matched controls; (2) PD patients with left-onset disease (right hemispheric impairment), report less detailed religious ritual action scripts; and (3) PD patients are less able to recall and access religious experiences. Our findings are consistent with adaptive theories of religion that point to evidence for functional design of religious cognition. C1 [Harris, Erica] Dept Neurol, Boston, MA 02130 USA. [Harris, Erica] Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02130 USA. [McNamara, Patrick] Inst Biocultural Study Relig, Dept Neurol, Boston, MA USA. RP Harris, E (reprint author), Dept Neurol, Jamaica Plain Campus, Boston, MA 02130 USA. EM erh8x@bu.edu; mcnamar@bu.edu NR 22 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1612-3018 BN 978-3-642-00127-7 J9 FRONT COLLECT PY 2009 BP 205 EP 215 DI 10.1007/978-3-642-00128-4_14 D2 10.1007/978-3-642-00128-4 PG 11 WC Evolutionary Biology; Religion SC Evolutionary Biology; Religion GA BLT27 UT WOS:000270976600014 ER PT J AU Gertz, MA Ghobrial, I Luc-Harousseau, J AF Gertz, Morie A. Ghobrial, Irene Luc-Harousseau, Jean TI Multiple Myeloma: Biology, Standard Therapy, and Transplant Therapy SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT Tandem Meeting on Biology of Blood and Marrow Transplantation CY FEB 11-15, 2009 CL Tampa, FL SP Amer Soc Blood & Marrow Transplantat DE multiple myeloma; Stem Cell Transplantation; Chemotherapy; genetics ID RANDOMIZED CONTROLLED-TRIAL; STEM-CELL TRANSPLANTATION; NEWLY-DIAGNOSED MYELOMA; AUTOLOGOUS TRANSPLANTATION; ELDERLY-PATIENTS; ORAL MELPHALAN; THALIDOMIDE; PREDNISONE; LENALIDOMIDE; BORTEZOMIB AB The understanding of the pathogenesis of multiple myeloma has undergone a major transformation over the past eight years. New insights into the microenvironment of the plasma cell as well as elucidation of signaling pathways that prevent plasma cell apoptosis are leading to rapid new drug development. The introduction of novel agents has led to a significant increase in survival. Combinations of novel agents are expected to provide higher complete response rate with anticipated prolongation of relapse free and overall survival. Autologous and allogeneic stem cell transplantation remains an integral part of therapy further improving the outcomes following induction with novel agents. C1 [Gertz, Morie A.] Mayo Clin, Div Hematol, Dept Med, Rochester, MN 55905 USA. [Ghobrial, Irene] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Luc-Harousseau, Jean] Univ Hosp Ctr, Dept Hematol, Nantes 01, France. RP Gertz, MA (reprint author), Mayo Clin, Div Hematol, Dept Med, 200 1st St SW, Rochester, MN 55905 USA. EM gertz.morie@mayo.edu FU NCI NIH HHS [R01 CA125690-01A2, R01 CA125690] NR 40 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2009 VL 15 IS 1 BP 46 EP 52 DI 10.1016/j.bbmt.2008.10.006 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 402SV UT WOS:000263034300012 PM 19147078 ER PT J AU Vesole, DH Zhang, LJ Flomenberg, N Greipp, PR Lazarus, HM AF Vesole, David H. Zhang, Lijun Flomenberg, Neal Greipp, Philip R. Lazarus, Hillard M. CA ECOG Myeloma BMT Committ TI A Phase II Trial of Autologous Stem Cell Transplantation Followed by Mini-Allogeneic Stem Cell Transplantation for the Treatment of Multiple Myeloma: An Analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol DE Multiple myeloma; Stem cell transplantation; Autologous; Allogeneic ID NEWLY-DIAGNOSED MYELOMA; COMPLETE REMISSION RATE; MARROW TRANSPLANTATION; PROGNOSTIC-FACTORS; RISK; THERAPY; BORTEZOMIB; BLOOD; DEXAMETHASONE; CURE AB Conventional allogeneic hematopoietic stem cell transplantation (HSCT) for multiple myeloma is associated with high transplantation-related mortality (TRM). Nonmyeloablative allogeneic transplantation (NST) uses the well-known graft-versus-myeloma (GVM) effect to eradicate minimal residual disease. The Eastern Cooperative Oncology Group conducted a Phase II trial of autologous HSCT followed by NST to provide maximal tumor cytoreduction to allow for a subsequent GVM effect. Patients received melphalan 200 mg/m(2) with autologous HSCT, followed by fludarabine 30 mg/m(2) in 5 daily doses and cyclophosphamide 1 g/m(2) in 2 daily doses with matched sibling donor NST Graft-versus-host disease (GVHD) prophylaxis included cyclosporine and corticosteroids. The primary endpoints were TRM, graft failure, acute GVHD, progression-free survival (PFS), and overall survival (OS). Thirty-two patients were enrolled into the study; 23 patients completed both transplantations (72%). Best responses post-NST were 7 (30%) complete remission (CR), 11 (48%) partial remission (PR), 2 (9%) no response, and 3 (13%) not evaluable. Acute grade III-IV GVHD was observed in 4 patients (17%), and chronic GVHD was seen in 13 patients (57%; 7 limited, 6 extensive). Chronic GVHD resulted in the following responses: 3 (23%) CR, I continuing CR, and 6 (46%) PR. Two patients (8.7%) had early TRM. With a median follow up of 4.6 years, the median PFS was 3.6 years, and the 2-year OS was 78%. Our findings indicate that autologous HSCT followed by NST is feasible, with a low early TRM in a cooperative group setting. The overall response rate was 78%, including 30% CR, similar to other reports for autologous HSCT-NST Because a plateau in PFS or OS was not observed with this treatment approach even in patients achieving CR, we suggest that future studies use posttransplantation maintenance therapy. C1 [Vesole, David H.] St Vincents Comprehens Canc Ctr, Dept Med, New York, NY USA. [Zhang, Lijun] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Flomenberg, Neal] Thomas Jefferson Univ, Dept Med, Kimmel Can Ctr, Philadelphia, PA 19107 USA. [Greipp, Philip R.] Mayo Clin, Dept Med, Rochester, MN USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. RP Vesole, DH (reprint author), Loyola Univ Chicago, Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. EM dvesole@lumc.edu FU NCI NIH HHS [U10 CA066636, U10 CA013650, U10 CA014548, U10 CA021115, U10 CA023318] NR 32 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2009 VL 15 IS 1 BP 83 EP 91 DI 10.1016/j.bbmt.2008.10.030 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 400NJ UT WOS:000262874700010 PM 19135946 ER PT J AU Tilly, JL Niikura, Y Rueda, BR AF Tilly, Jonathan L. Niikura, Yuichi Rueda, Bo R. TI The Current Status of Evidence for and Against Postnatal Oogenesis in Mammals: A Case of Ovarian Optimism Versus Pessimism? SO BIOLOGY OF REPRODUCTION LA English DT Review DE atresia; fertility; follicle; germ cell; oocyte; oogenesis; ovary; stem cells ID EMBRYONIC STEM-CELLS; BONE-MARROW-TRANSPLANTATION; HUMAN CEREBRAL-CORTEX; TOTAL-BODY IRRADIATION; INITIAL FOLLICLE POOL; PRIMORDIAL GERM-CELLS; ADULT-MOUSE OVARY; IN-VITRO; HEMATOLOGICAL MALIGNANCIES; PERIPHERAL-BLOOD AB Whether or not oogenesis continues in the ovaries of mammalian females during postnatal life was heavily debated from the late 1800s through the mid-1900s. However, in 1951 Lord Solomon Zuckerman published what many consider to be a landmark paper summarizing his personal views of data existing at the time for and against the possibility of postnatal oogenesis. In Zuckerman's opinion, none of the evidence he considered was inconsistent with Waldeyer's initial proposal in 1870 that female mammals cease production of oocytes at or shortly after birth. This conclusion rapidly became dogma, and remained essentially unchallenged until just recently, despite the fact that Zuckerman did not offer a single experiment proving that adult female mammals are incapable of oogenesis. Instead, 20 years later he reemphasized that his conclusion was based solely on an absence of data he felt would be inconsistent with the idea of a nonrenewable oocyte pool provided at birth. However, in the immortal words of Carl Sagan, an "absence of evidence is not evidence of absence.'' Indeed, building on the efforts of a few scientists who continued to question this dogma after Zuckerman's treatise in 1951, we reported several data sets in 2004 that were very much inconsistent with the widely held belief that germ cell production in female mammals ceases at birth. Perhaps not surprisingly, given the magnitude of the paradigm shift being proposed, this work reignited a vigorous debate that first began more than a century ago. Our purpose here is to review the experimental evidence offered in recent studies arguing support for and against the possibility that adult mammalian females replenish their oocyte reserve. "Never discourage anyone who continually makes progress, no matter how slow.''-Plato (427-347 BC). C1 [Tilly, Jonathan L.; Niikura, Yuichi; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Sch Med,Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Sch Med,Vincent Obstet & Gynecol Serv, THR-901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU National Institutes of Health [R01-AG024999, R37-AG012279, R01-CA98333]; Rubin Shulsky Philanthropic Fund; Henry and Vivian Rosenberg Philanthropic Fund; Sea Breeze Foundation; JM Foundation; Vincent Memorial Research Funds FX Supported by the National Institutes of Health grants R01-AG024999 and R37-AG012279 to J. L. T. and R01-CA98333 to B. R. R., the Rubin Shulsky Philanthropic Fund, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, the JM Foundation, and Vincent Memorial Research Funds. NR 122 TC 56 Z9 62 U1 3 U2 14 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2009 VL 80 IS 1 BP 2 EP 12 DI 10.1095/biolreprod.108.069088 PG 11 WC Reproductive Biology SC Reproductive Biology GA 388HE UT WOS:000262010100001 PM 18753611 ER PT J AU Eroglu, A Bailey, SE Toner, M Toth, TL AF Eroglu, Ali Bailey, Sarah E. Toner, Mehmet Toth, Thomas L. TI Successful Cryopreservation of Mouse Oocytes by Using Low Concentrations of Trehalose and Dimethylsulfoxide SO BIOLOGY OF REPRODUCTION LA English DT Article DE freezing; glass transition temperature; in vitro fertilization; microinjection; oocyte cryopreservation; sugar; trehalose ID EMBRYO TRANSFER PROGRAM; SLOW-FREEZING METHOD; IN-VITRO; SUCROSE CONCENTRATION; MICROINJECTED TREHALOSE; DESICCATION TOLERANCE; DIMETHYL-SULFOXIDE; PROTECTIVE ACTION; VITRIFICATION; SURVIVAL AB Sugars such as trehalose, sucrose, and glucose are effectively used by a variety of animals (e.g., brine shrimp, tardigrades, some frogs, and insects), as well as by bacteria, yeasts, and plant seeds to survive freezing and extreme drying. The objective of this study was to examine the potential application of sugars to mammalian oocyte cryopreservation. To this end, we used trehalose, a nonreducing disaccharide, and mouse metaphase II oocytes as models. Our experiments show that extracellular trehalose alone affords some protection at high subzero temperatures (e.g., -15 degrees C), which diminishes with further cooling of the oocytes to -30 degrees C and below. When present both intracellularly and extracellularly, trehalose dramatically improves the cryosurvival with increasing extracellular concentrations to 0.5 M, even after cooling to -196 degrees C. Furthermore, the combination of intracellular and extracellular trehalose with small amounts of a conventional penetrating cryoprotectant (i.e., 0.5 M dimethylsulfoxide) provide high survival, fertilization, and embryonic development rates statistically similar to untreated controls. When transferred to foster mothers, cryopreserved oocytes give rise to healthy offspring showing the proof of principle. Our experiments with differential scanning calorimetry indicate that when cooled using the same cryopreservation protocol, the mixture of 0.5 M trehalose and cryopreservation medium undergoes glass transition at high subzero temperatures, which further substantiates the use of sugars as intracellular and extracellular cryoprotectants. Taken together, our results are in agreement with the survival schemes in nature and demonstrate the successful use of sugars in cryopreservation of mammalian oocytes. C1 [Eroglu, Ali; Bailey, Sarah E.] Med Coll Georgia, Inst Mol Med & Genet, Dept Med, Augusta, GA 30912 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Toth, Thomas L.] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Eroglu, A (reprint author), 1120 15th St,CB-2803, Augusta, GA 30912 USA. EM aeroglu@mcg.edu FU National Institute Of Child Health and Human Development [R01HD049537] FX Supported by grant R01HD049537 from the National Institute Of Child Health and Human Development to A. E. NR 74 TC 33 Z9 34 U1 1 U2 15 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2009 VL 80 IS 1 BP 70 EP 78 DI 10.1095/biolreprod.108.070383 PG 9 WC Reproductive Biology SC Reproductive Biology GA 388HE UT WOS:000262010100008 PM 18815355 ER PT J AU Belleannee, C Da Silva, N Shum, WWC Marsolais, M Laprade, R Brown, D Breton, S AF Belleannee, C. Da Silva, N. Shum, W. W. C. Marsolais, M. Laprade, R. Brown, D. Breton, S. TI Segmental Expression of the Bradykinin Type 2 Receptor in Rat Efferent Ducts and Epididymis and Its Role in the Regulation of Aquaporin 9 SO BIOLOGY OF REPRODUCTION LA English DT Article DE bradykinin receptor; efferent ducts; epididymis; male reproductive tract; water channel ID MALE REPRODUCTIVE-TRACT; TRANSMEMBRANE CONDUCTANCE REGULATOR; ANGIOTENSIN-CONVERTING ENZYME; KALLIKREIN-KININ SYSTEM; V-ATPASE; MALE-FERTILITY; VAS-DEFERENS; ANION SECRETION; BLOOD-PRESSURE; B-2 RECEPTOR AB Water and solute transport in the efferent ducts and epididymis are important for the establishment of the appropriate luminal environment for sperm maturation and storage. Aquaporin 9 (AQP9) is the main water channel in the epididymis, but its regulation is still poorly understood. Components of the kinin-kallikrein system (KKS), leading to the production of bradykinin (BK), are highly expressed in the lumen of the male reproductive tract. We report here that the epididymal luminal fluid contains a significant amount of BK (2 nM). RT-PCR performed on epididymal epithelial cells isolated by laser capture microdissection (LCM) showed abundant BK type 2 receptor (Bdkrb2) mRNA expression but no type 1 receptor (Bdkrb1). Double-immunofluorescence staining for BDKRB2 and the anion exchanger AE2 (a marker of efferent duct ciliated cells) or the V-ATPase E subunit, official symbol ATP6V1E1 (a marker of epididymal clear cells), showed that BDKRB2 is expressed in the apical pole of nonciliated cells (efferent ducts) and principal cells (epididymis). Triple labeling for BDKRB2, AQP9, and ATP6V1E1 showed that BDKRB2 and AQP9 colocalize in the apical stereocilia of principal cells in the cauda epididymidis. While uniform Bdkrb2 mRNA expression was detected in the efferent ducts and along the epididymal tubule, marked variations were detected at the protein level. BDKRB2 was highest in the efferent ducts and cauda epididymidis, intermediate in the distal initial segment, moderate in the corpus, and undetectable in the proximal initial segment and the caput. Functional assays on tubules isolated from the distal initial segments showed that BK significantly increased AQP9-dependent glycerol apical membrane permeability. This effect was inhibited by BAPTA-AM, demonstrating the participation of calcium in this process. This study, therefore, identifies BK as an important regulator of AQP9. C1 [Belleannee, C.; Da Silva, N.; Shum, W. W. C.; Brown, D.; Breton, S.] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. [Marsolais, M.; Laprade, R.] Univ Montreal, Grp Etud Prot Membranaires, Montreal, PQ H3C 3J7, Canada. RP Breton, S (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Simches Res Ctr, 185 Cambridge St,CPZN 8-204, Boston, MA 02114 USA. EM breton.sylvie@mgh.harvard.edu FU National Institutes of Health [HD045821]; Center for the Study of Inflammatory Bowel Disease [DK43351]; Boston Area Diabetes and Endocrinology Research Center [DK57521] FX Supported by National Institutes of Health grant HD045821 to S. B. The work performed in the Microscopy Core Facility of the Massachusetts General Hospital Program in Membrane Biology was supported by Center for the Study of Inflammatory Bowel Disease grant DK43351 and Boston Area Diabetes and Endocrinology Research Center award DK57521. NR 64 TC 14 Z9 14 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2009 VL 80 IS 1 BP 134 EP 143 DI 10.1095/biolreprod.108.070797 PG 10 WC Reproductive Biology SC Reproductive Biology GA 388HE UT WOS:000262010100015 PM 18829705 ER PT J AU Belleannee, C Da Silva, N Shum, W Breton, S AF Belleannee, Clemence Da Silva, Nicolas Shum, Winnie Breton, Sylvie TI Role of Luminal ATP and Adenosine on V-ATPase Activation via Purinergic Receptors P1 and P2 in Mouse and Rat Epididymis. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Belleannee, Clemence; Da Silva, Nicolas; Shum, Winnie; Breton, Sylvie] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 21 BP 52 EP 52 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500021 ER PT J AU Selesniemi, K Lee, HJ Tilly, JL AF Selesniemi, Kaisa Lee, Ho-Joon Tilly, Jonathan L. TI Adult-Onset Calorie Restriction Prevents Age-Related Decline in Oocyte Yield and Quality SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Selesniemi, Kaisa; Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 138 BP 78 EP 78 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500137 ER PT J AU Rueda, BR Sakamoto, H Curley, MD Blok, LJ Taylor, RN AF Rueda, Bo R. Sakamoto, Hideo Curley, Michael D. Blok, Leen J. Taylor, Robert N. TI Cables 1 Interacts with p300 to Regulate Progesterone-Induced Endometrial Glycodelin Expression SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 315 BP 119 EP 119 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500303 ER PT J AU Bosukonda, A Rehman, F Mallette, SA Sluss, PM AF Bosukonda, Ashish Rehman, Farah Mallette, Sheila A. Sluss, Patrick M. TI Bone Morphogenetic Protein-6 (BMP-6) Efficacy and Its Mechanism of Action to Suppress Human Prostate Cancer Cell Growth. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. BioSci Res Labs, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 372 BP 132 EP 132 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500359 ER PT J AU Harel, NY Cudkowicz, ME Brown, RH Strittmatter, SM AF Harel, Noam Y. Cudkowicz, Merit E. Brown, Robert H. Strittmatter, Stephen M. TI Serum Nogo-A levels are not elevated in amyotrophic lateral sclerosis patients SO BIOMARKERS LA English DT Article DE ALS; Nogo-A; biomarker; DELFIA; ELISA ID MUSCLE; EXPRESSION; RECEPTOR; MARKER; ALS; IDENTIFICATION; SEVERITY; PROTEINS AB Improved biomarkers would facilitate the diagnosis and treatment of amyotrophic lateral sclerosis (ALS). Muscle content of the neuritic outgrowth inhibitor Nogo-A is increased in patients with ALS and other denervating conditions. Seeking a less invasive diagnostic method, we sought to determine whether or not Nogo increases in the serum of ALS patients. We developed a dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) protocol to screen serum samples from 172 ALS patients and 172 healthy controls for Nogo-A immunoreactivity. Unexpectedly, there was a trend toward decreased levels of serum Nogo-A in ALS. Mean serum Nogo-A level in ALS patients was 0.71 nM (95% confidence interval (CI) 0.42-1.00), as opposed to 1.15 nM (95% CI 0.72-1.59) in healthy controls. A significantly larger percentage of healthy control sera (11.0% vs 4.7%) displayed markedly elevated levels of Nogo-A. Additional study is required to determine the factors that lead to elevated Nogo-A levels in a subset of both ALS patients and healthy controls. C1 [Harel, Noam Y.; Strittmatter, Stephen M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Cudkowicz, Merit E.; Brown, Robert H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Strittmatter, Stephen M.] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT USA. RP Harel, NY (reprint author), Yale Univ, Sch Med, Dept Neurol, POB 208018, New Haven, CT 06520 USA. EM noam.harel@yale.edu OI Strittmatter, Stephen/0000-0001-8188-3092 FU NINDS [K08 NS056212]; Falk Medical Research Trust; ALS Association FX We thank Zhengrong Hao and William C. Sessa for sharing their Nogo-BELISA protocol, and Galen-Royce-Nagel and Patrick Butsch for assistance in obtaining serum samples. We thank the reviewers for excellent comments and suggestions. This work was supported by grants from the NINDS (K08 NS056212), the Falk Medical Research Trust, and the ALS Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. N.Y.H. and S. M. S. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All the authors certify that no financial conflicts of interest relative to this manuscript are present. NR 18 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PY 2009 VL 14 IS 6 BP 414 EP 417 DI 10.1080/13547500903056051 PG 4 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 507ON UT WOS:000270864100009 PM 19548774 ER PT J AU Melo, N Sheridan, R AF Melo, N. Sheridan, R. BE Orgill, DP Blanco, C TI Lyophilized xenogenic products for skin replacement SO BIOMATERIALS FOR TREATING SKIN LOSS SE Woodhead Publishing in Materials LA English DT Article; Book Chapter DE lyophilized xenogenic skin substitutes; porcine dermis; bovine dermis; porcine small intestine submucosa ID SMALL-INTESTINAL SUBMUCOSA; EXTRACELLULAR-MATRIX; ARTIFICIAL SKIN; HERNIA REPAIR; SUBSTITUTES; SURGISIS; WOUNDS; GRAFT; DRESSINGS; PATCHES AB This chapter describes the need for purified skin substitutes derived from animals. It discusses the difference in products for temporary and permanent skin replacement. Using both porcine and bovine derivatives, skin and tissue replacement has been performed safely, effectively and in most areas of the human body, with great results. C1 [Melo, N.; Sheridan, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Dept Surg,Div Burns, Boston, MA 02114 USA. RP Melo, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Dept Surg,Div Burns, 55 Fruit St, Boston, MA 02114 USA. EM nmelo@partners.org; sheridan.robert@mgh.harvard.edu NR 36 TC 0 Z9 0 U1 0 U2 0 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND BN 978-1-84569-363-3 J9 WOODHEAD PUBL MATER PY 2009 BP 174 EP 180 PG 7 WC Cell & Tissue Engineering; Materials Science, Biomaterials; Surgery SC Cell Biology; Materials Science; Surgery GA BOP70 UT WOS:000277247400011 ER PT S AU Mroz, P Castano, AP Hamblin, MR AF Mroz, Pawel Castano, Ana P. Hamblin, Michael R. BE Chen, WR TI Stimulation of dendritic cells enhances immune response after photodynamic therapy SO BIOPHOTONICS AND IMMUNE RESPONSES IV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses IV CY JAN 25-26, 2009 CL San Jose, CA SP SPIE DE CpG oligodeoxynucleotide; dendritic cells; toll like receptors; anti-tumor immunity; photodynamic therapy ID HEAT-SHOCK PROTEINS; ANTITUMOR IMMUNITY; IN-VIVO; CPG-DNA; TUMOR; ACTIVATION; OLIGONUCLEOTIDES; NEUTROPHILS; EXPRESSION; INDUCTION AB Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naive T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction. C1 [Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 34 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7424-7 J9 PROC SPIE PY 2009 VL 7178 AR 717803 DI 10.1117/12.809630 PG 10 WC Engineering, Biomedical; Immunology; Optics SC Engineering; Immunology; Optics GA BSS65 UT WOS:000285713800001 ER PT J AU Verdine, G AF Verdine, G. TI DRUGGING "UNDRUGGABLE" TARGETS USING STAPLED PEPTIDES SO BIOPOLYMERS LA English DT Meeting Abstract CT 21st American Peptide Symposium CY JUN 07-12, 2009 CL Bloomington, IN SP Amer Peptide Soc ID BH3 HELIX C1 [Verdine, G.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Verdine, G.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Verdine, G.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Verdine, G.] Dana Farber Canc Inst, Chem Biol Initiat, Cambridge, MA 02138 USA. [Verdine, G.] Dana Farber Canc Inst, Program Canc Chem Biol, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu NR 4 TC 1 Z9 1 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 4 BP 296 EP 296 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455IU UT WOS:000266753100020 ER PT J AU Chen, S Bouley, R Vilardaga, J Aussiello, D Khatri, A AF Chen, S. Bouley, R. Vilardaga, J. Aussiello, D. Khatri, A. TI SYNTHESIS AND BIOLOGICAL CHARACTERIZATION OF NOVEL FLUORESCENT ANALOGS OF VASOPRESSIN SO BIOPOLYMERS LA English DT Meeting Abstract CT 21st American Peptide Symposium CY JUN 07-12, 2009 CL Bloomington, IN SP Amer Peptide Soc C1 [Chen, S.; Bouley, R.; Vilardaga, J.; Aussiello, D.; Khatri, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, S.; Bouley, R.; Vilardaga, J.; Aussiello, D.; Khatri, A.] Harvard Univ, Sch Med, Boston, MA USA. [Vilardaga, J.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 4 BP 361 EP 362 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455IU UT WOS:000266753100339 ER PT J AU Khatri, A Potts, J Martin, TJ Gardella, T AF Khatri, A. Potts, J. Martin, T. J. Gardella, T. TI CHEMICAL SYNTHESIS OF FULL-LENGTH PARATHYROID HORMONE-RELATED PROTEIN-(1-141) SO BIOPOLYMERS LA English DT Meeting Abstract CT 21st American Peptide Symposium CY JUN 07-12, 2009 CL Bloomington, IN SP Amer Peptide Soc C1 [Khatri, A.; Potts, J.; Gardella, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Khatri, A.; Potts, J.; Gardella, T.] Harvard Univ, Sch Med, Boston, MA USA. [Martin, T. J.] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 4 BP 370 EP 370 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455IU UT WOS:000266753100384 ER PT J AU Donahoe, PK Noonan, KM Lage, K AF Donahoe, Patricia K. Noonan, Kristin M. Lage, Kasper TI Genetic Tools and Algorithms for Gene Discovery in Major Congenital Anomalies SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Editorial Material ID NEURAL-TUBE DEFECTS; COMPARATIVE GENOMIC HYBRIDIZATION; DIAPHRAGMATIC-HERNIA CDH; BIRTH-DEFECTS; SONIC HEDGEHOG; RETINOIC ACID; FOLIC-ACID; NETWORK; ASSOCIATION; RECURRENCE C1 [Donahoe, Patricia K.; Noonan, Kristin M.; Lage, Kasper] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Donahoe, Patricia K.; Noonan, Kristin M.; Lage, Kasper] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Lage, Kasper] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, 185 Cambridge St, Boston, MA 02114 USA. EM donahoe.patricia@mgh.harvard.edu FU NICHD NIH HHS [R01 HD055150, HD 055150, R01 HD055150-03] NR 46 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JAN PY 2009 VL 85 IS 1 BP 6 EP 12 DI 10.1002/bdra.20546 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 400YH UT WOS:000262904800002 PM 19107955 ER PT J AU Owen, MH Ryan, LM Holmes, LB AF Owen, Mary H. Ryan, Louise M. Holmes, Lewis B. TI Effects of Retinoic Acid on Dominant bemimelia Expression in Mice SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE Dominant hemimelia; retinoic acid; axial patterning ID RANGE SHH ENHANCER; RESPONSE ELEMENT; FUNCTIONAL-ANALYSIS; MOUSE EMBRYO; HOX GENES; IN-VIVO; HEMIMELIA; HINDBRAIN; LIMB; CDX1 AB BACKGROUND: Dominant hemimelia (Dh) is an autosomal dominant mutation that arose spontaneously in mice. Dh animals are asplenic and they exhibit asymmetric hindlimb defects in association with reduced numbers of lumbar vertebrae. These defects suggest that Dh acts early in embryonic development to affect patterning of the anterior-posterior (A-P) and left-right axes. This study was undertaken to determine whether retinoic acid (RA), which is involved in A-P patterning and coordination of bilaterally synchronized somitogenesis, affects phenotypic expression of the Dh gene. METHODS: Thirty-four pregnant females were given, by oral intubation, a single dose of 50 or 75 mg all-trans RA per kilogram body weight at GD 9, 10, or 11. The pregnant females were then euthanized at GD 18 and fetuses removed by cesarean section. A total of 326 fetuses were identified by phenotype and linked DNA and their skeletons were analyzed. RESULTS: There was a differential effect of RA on the axial skeleton and hindlimb of Dh/+ mice as compared to their wild-type littermates. Dose- and stage-specific effects on sternebrae and vertebrae were observed. CONCLUSIONS: The effects of RA dosing on numbers of sternebrae and vertebrae suggest that Dh embryos have a primary defect in retinoid-mediated A-P patterning. Dosing with RA may produce the observed effects on phenotypic expression of Dh/+ by indirectly or directly modifying an already existing altered Hox expression pattern. As the relationship between axial patterning and the asymmetric limb is unknown, Dh is an important model for studying this relationship. Birth Defects Research (Part A) 85:36-41, 2009, (C) 2008 Wiley-Liss, Inc. C1 [Owen, Mary H.] Simmons Coll, Dept Biol, Boston, MA 02115 USA. [Owen, Mary H.; Holmes, Lewis B.] MassGen Hosp Children, Genet Unit, Boston, MA USA. [Holmes, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ryan, Louise M.] Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. RP Owen, MH (reprint author), Simmons Coll, Dept Biol, 300 Fenway, Boston, MA 02115 USA. EM mary.owen@simmons.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU Peabody Foundation, Boston, MA FX Grant sponsor: Peabody Foundation, Boston, MA. NR 35 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JAN PY 2009 VL 85 IS 1 BP 36 EP 41 DI 10.1002/bdra.20528 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 400YH UT WOS:000262904800006 PM 19086026 ER PT J AU Pober, BR Longoni, M Noonan, KM AF Pober, Barbara R. Longoni, Mauro Noonan, Kristin M. TI A Review of Donnai-Barrow and Facio-oculo-acoustico-renal (DB/FOAR) Syndrome: Clinical Features and Differential Diagnosis SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Review DE Donnai-Barrow (DB) syndrome; facio-oculo-acoustico-renal (FOAR); syndrome; LRP2; megalin; congenital diaphragmatic hernia; agenesis of corpus callosum ID AUTOSOMAL RECESSIVE INHERITANCE; ABSENT CORPUS-CALLOSUM; DIAPHRAGMATIC-HERNIA; SENSORINEURAL DEAFNESS; MEGALIN; HYPERTELORISM; EXOMPHALOS; MYOPIA; PATIENT; LRP2 AB Mutations in the gene LRP2 have recently been identified as the cause of Donnai-Barrow and Facio-oculo-acoustico-renal (DB/FOAR) syndrome. More than two dozen cases, the first reported more than 30 years ago by Holmes, have been published. Summarizing available information, we highlight the cardinal features of the disorder found in >= 90% of published cases. These features include: agenesis of the corpus callosum, developmental delay, enlarged anterior fontanelle, high myopia, hypertelorism, proteinuria, and sensorineural hearing loss. Congenital diaphragmatic hernia and omphalocele are reported in only half of the patients. There is no evidence for genotype-phenotype correlation, though the sample size is too small to preclude this with certainty. Although several conditions to consider in the differential diagnosis are highlighted, the diagnosis of DB/FOAR syndrome should not be difficult to establish as its constellation of findings is strikingly characteristic. Birth Defects Research (Part A) 85:76-81, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Pober, Barbara R.] Massachusetts Gen Hosp, Ctr Human Genet, Pediat Lab, Boston, MA 02115 USA. [Longoni, Mauro; Noonan, Kristin M.] Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02115 USA. [Pober, Barbara R.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Pober, Barbara R.; Longoni, Mauro; Noonan, Kristin M.] Harvard Univ, Sch Med, Boston, MA USA. RP Pober, BR (reprint author), Massachusetts Gen Hosp, Ctr Human Genet, Pediat Lab, Simches Res Bldg,185 Cambridge St, Boston, MA 02115 USA. EM pober.barbar@mgh.harvard.edu RI Longoni, Mauro/I-2526-2013 FU American College of Surgeons' Resident Research Award; [R01 HD55150-01] FX These authors are supported by R01 HD55150-01. KMN is also supported by the 2006 American College of Surgeons' Resident Research Award. NR 19 TC 24 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JAN PY 2009 VL 85 IS 1 BP 76 EP 81 DI 10.1002/bdra.20534 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 400YH UT WOS:000262904800012 PM 19089858 ER PT J AU Zenhaeusern, G Gubser, P Eisele, P Gasser, O Steinhuber, A Trampuz, A Handschin, C Luster, AD Hess, C AF Zenhaeusern, Gabriela Gubser, Patrick Eisele, Petra Gasser, Olivier Steinhuber, Andrea Trampuz, Andrej Handschin, Christoph Luster, Andrew D. Hess, Christoph TI A high-mobility, low-cost phenotype defines human effector-memory CD8(+) T cells SO BLOOD LA English DT Article ID LYMPHOCYTE MOTILITY; ACTIVATION; MIGRATION; IMMUNITY; NODES; SURVIVAL; SUBSETS; CD44 AB T cells move randomly ("random-walk"), a characteristic thought to be integral to their function. Using migration assays and time-lapse microscopy, we found that CD8(+) T cells lacking the lymph node homing receptors CCR7 and CD62L migrate more efficiently in transwell assays, and that these same cells are characterized by a high frequency of cells exhibiting random crawling activity under culture conditions mimicking the interstitial/extravascular milieu, but not when examined on endothelial cells. To assess the energy efficiency of cells crawling at a high frequency, we measured mRNA expression of genes key to mitochondrial energy metabolism ( peroxisome proliferator-activated receptor gamma coactivator 1 beta [PGC-1 beta], estrogen-related receptor alpha [ERR alpha], cytochrome C, ATP synthase, and the uncoupling proteins [UCPs] UCP-2 and -3), quantified ATP contents, and performed calorimetric analyses. Together these assays indicated a high energy efficiency of the high crawling frequency CD8(+) T-cell population, and identified differentially regulated heat production among nonlymphoid versus lymphoid homing CD8(+) T cells. (Blood. 2009; 113: 95-99) C1 [Hess, Christoph] Univ Basel Hosp, Dept Biomed, Immunobiol Lab, CH-4031 Basel, Switzerland. [Eisele, Petra; Handschin, Christoph] Univ Zurich, Inst Physiol, Lab Skeletal Muscle Biol, Zurich, Switzerland. [Gasser, Olivier] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. [Steinhuber, Andrea; Trampuz, Andrej] Univ Basel Hosp, Infectiol Lab, CH-4031 Basel, Switzerland. [Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Charlestown, MA USA. RP Hess, C (reprint author), Univ Basel Hosp, Dept Biomed, Immunobiol Lab, 20 Hebelstr, CH-4031 Basel, Switzerland. EM chess@uhbs.ch RI Gasser, Olivier/I-3663-2013; Trampuz, Andrej/K-9633-2013; Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU Swiss National Science Foundation (SNF) [PP00B-114850] FX C. H. was supported by the Swiss National Science Foundation (SNF professorship grant PP00B-114850). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 24 TC 1 Z9 1 U1 0 U2 2 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 JAN 1 PY 2009 VL 113 IS 1 BP 95 EP 99 DI 10.1182/blood-2008-04-153262 PG 5 WC Hematology SC Hematology GA 390KN UT WOS:000262162800016 PM 18845792 ER PT J AU Shah, SP Epino, H Bukhman, G Umulisa, I Dushimiyimana, JMV Reichman, A Noble, VE AF Shah, Sachita P. Epino, Henry Bukhman, Gene Umulisa, Irenee Dushimiyimana, J. M. V. Reichman, Andrew Noble, Vicki E. TI Impact of the introduction of ultrasound services in a limited resource setting: rural Rwanda 2008 SO BMC INTERNATIONAL HEALTH AND HUMAN RIGHTS LA English DT Article AB Background: Over the last decade, utilization of ultrasound technology by non-radiologist physicians has grown. Recent advances in affordability, durability, and portability have brought ultrasound to the forefront as a sustainable and high impact technology for use in developing world clinical settings as well. However, ultrasound's impact on patient management plans, program sustainability, and which ultrasound applications are useful in this setting has not been well studied. Methods: Ultrasound services were introduced at two rural Rwandan district hospitals affiliated with Partners in Health, a US nongovernmental organization. Data sheets for each ultrasound scan performed during routine clinical care were collected and analyzed to determine patient demographics, which ultrasound applications were most frequently used, and whether the use of the ultrasound changed patient management plans. Ultrasound scans performed by the local physicians during the post-training period were reviewed for accuracy of interpretation and image quality by an ultrasound fellowship trained emergency medicine physician from the United States who was blinded to the original interpretation. Results: Adult women appeared to benefit most from the presence of ultrasound services. Of the 345 scans performed during the study period, obstetrical scanning was the most frequently used application. Evaluation of gestational age, fetal head position, and placental positioning were the most common findings. However, other applications used included abdominal, cardiac, renal, pleural, procedural guidance, and vascular ultrasounds. Ultrasound changed patient management plans in 43% of total patients scanned. The most common change was to plan a surgical procedure. The ultrasound program appears sustainable; local staff performed 245 ultrasound scans in the 11 weeks after the departure of the ultrasound instructor. Post-training scan review showed the concordance rate of interpretation between the Rwandese physicians and the ultrasound-trained quality review physicians was 96%. Conclusion: We suggest ultrasound is a useful modality that particularly benefits women's health and obstetrical care in the developing world. Ultrasound services significantly impact patient management plans especially with regards to potential surgical interventions. After an initial training period, it appears that an ultrasound program led by local health care providers is sustainable and lead to accurate diagnoses in a rural international setting. C1 [Shah, Sachita P.] Alameda Cty Med Ctr, Dept Emergency Med, Oakland, CA USA. [Epino, Henry; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Bukhman, Gene] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Umulisa, Irenee; Dushimiyimana, J. M. V.; Reichman, Andrew] Kirehe Hosp, Kirehe, Eastern Prov, Rwanda. RP Shah, SP (reprint author), Alameda Cty Med Ctr, Dept Emergency Med, 1411 E 31st St, Oakland, CA USA. EM sachita.shah@gmail.com; hepino@pih.org; gbukhman@gmail.com; umulisa5@yahoo.fr; dushimiyimana@gmail.com; reichman.andrew@gmail.com; vnoble@partners.org NR 9 TC 35 Z9 35 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-698X J9 BMC INT HEALTH HUM R JI BMC Int. Health Hum. Rights. PY 2009 VL 9 AR 4 DI 10.1186/1472-698X-9-4 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V17AZ UT WOS:000207911400004 PM 19327157 ER PT J AU Ruger, JP Emmons, KM Kearney, MH Weinstein, MC AF Ruger, Jennifer Prah Emmons, Karen M. Kearney, Margaret H. Weinstein, Milton C. TI Measuring the costs of outreach motivational interviewing for smoking cessation and relapse prevention among low-income pregnant women SO BMC PREGNANCY AND CHILDBIRTH LA English DT Article AB Background: Economic theory provides the philosophical foundation for valuing costs in judging medical and public health interventions. When evaluating smoking cessation interventions, accurate data on costs are essential for understanding resource consumption. Smoking cessation interventions, for which prior data on resource costs are typically not available, present special challenges. We develop a micro-costing methodology for estimating the real resource costs of outreach motivational interviewing (MI) for smoking cessation and relapse prevention among low-income pregnant women and report results from a randomized controlled trial (RCT) employing the methodology. Methodological standards in cost analysis are necessary for comparison and uniformity in analysis across interventions. Estimating the costs of outreach programs is critical for understanding the economics of reaching underserved and hard-to-reach populations. Methods: Randomized controlled trial (1997-2000) collecting primary cost data for intervention. A sample of 302 low-income pregnant women was recruited from multiple obstetrical sites in the Boston metropolitan area. MI delivered by outreach health nurses vs. usual care (UC), with economic costs as the main outcome measures. Results: The total cost of the MI intervention for 156 participants was $48,672 or $312 per participant. The total cost of $311.8 per participant for the MI intervention compared with a cost of $4.82 per participant for usual care, a difference of $307 ([CI], $289.2 to $322.8). The total fixed costs of the MI were $3,930 and the total variable costs of the MI were $44,710. The total expected program costs for delivering MI to 500 participants would be 147,430, assuming no economies of scale in program delivery. The main cost components of outreach MI were intervention delivery, travel time, scheduling, and training. Conclusion: Grounded in economic theory, this methodology systematically identifies and measures resource utilization, using a process tracking system and calculates both component-specific and total costs of outreach MI. The methodology could help improve collection of accurate data on costs and estimates of the real resource costs of interventions alongside clinical trials and improve the validity and reliability of estimates of resource costs for interventions targeted at underserved and hard-to-reach populations. C1 [Ruger, Jennifer Prah] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Ruger, Jennifer Prah] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Emmons, Karen M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Community Based Res, Cambridge, MA 02138 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. [Kearney, Margaret H.] Univ Rochester, Med Ctr, Sch Nursing, Rochester, NY 14642 USA. [Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Weinstein, Milton C.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Ruger, JP (reprint author), Yale Univ, Sch Med, New Haven, CT 06520 USA. EM jennifer.ruger@yale.edu; karen_m_emmons@dcfi.harvard.edu; margaret_kearney@urmc.rochester.edu; mcw@hsph.harvard.edu OI Kearney, Margaret H/0000-0002-2671-7662 FU National Institutes of Health (NCI) [5R01CA073242-04]; National Institutes of Health (NIDA) [1K01DA01635810] FX This work was supported by a grant from the National Institutes of Health (NCI grant 5R01CA073242-04). Dr. Ruger is supported by a Career Development Award from the National Institutes of Health (NIDA grant 1K01DA01635810) NR 33 TC 13 Z9 13 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2393 J9 BMC PREGNANCY CHILDB JI BMC Pregnancy Childbirth PY 2009 VL 9 AR 46 DI 10.1186/1471-2393-9-46 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA V19YE UT WOS:000208106900046 PM 19775455 ER PT J AU Yusuf, RZ Dey, B Yeap, BY McAfee, S Attar, E Sepe, PS Dube, C Spitzer, TR Ballen, KK AF Yusuf, R. Z. Dey, B. Yeap, B. Y. McAfee, S. Attar, E. Sepe, P. S. Dube, C. Spitzer, T. R. Ballen, K. K. TI Autologous SCT with a dose-reduced BU and CY regimen in older patients with non-Hodgkin's lymphoma SO BONE MARROW TRANSPLANTATION LA English DT Article DE lymphoma; elderly; autologous SCT ID STEM-CELL TRANSPLANTATION; BONE-MARROW TRANSPLANTATION; PREPARATIVE REGIMEN; CONDITIONING REGIMEN; INTRAVENOUS BUSULFAN; AGGRESSIVE LYMPHOMA; MULTIPLE-MYELOMA; ELDERLY-PATIENTS; CYCLOPHOSPHAMIDE; BLOOD AB Autologous SCT is a potentially curative procedure for patients with relapsed lymphoma (NHL). We analyzed the outcomes of 34 patients >= 60 years old, including eight patients >= 70 years old, who received BU and CY and SCT for NHL. Patients received BU 0.8 mg/kg i.v. (n = 25) or 1 mg/kg p.o. (n = 9) q 6 h x 14 doses and CY 60 mg/kg i.v. q day x 2 days. The median age was 66 (range, 60-78) years. Twenty-two patients had large cell, 10 follicular and two-mantle cell lymphoma. Fifteen patients were in a second or greater CR and 19 patients were in a PR. The median days to ANC > 500/mu l and platelet count > 50 000/mu l were 10 and 13 days respectively. The 100-day transplant-related mortality was 0%. Toxicities included interstitial lung disease (n = 2), seizures in a patient with CNS lymphoma (n = 1), mild veno-occlusive disease (n = 2), and transient atrial fibrillation (n = 4). With a median follow-up of 40 months, the 2-year overall survival and PFS were 67 and 54% respectively. BU/CY is a well-tolerated conditioning regimen for older patients with NHL. Age alone should not be used as an exclusion criterion for autologous SCT. C1 [Yusuf, R. Z.; Dey, B.; Yeap, B. Y.; McAfee, S.; Attar, E.; Sepe, P. S.; Dube, C.; Spitzer, T. R.; Ballen, K. K.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Suite 118, Boston, MA 02114 USA. EM ballen@partners.org NR 30 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2009 VL 43 IS 1 BP 37 EP 42 DI 10.1038/bmt.2008.298 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 394YT UT WOS:000262489800005 PM 18794868 ER PT B AU Reinus, WR Kattapuram, SV Khurana, JS AF Reinus, William R. Kattapuram, Susan V. Khurana, Jasvir S. BE Khurana, JS TI Radiology of the Musculoskeletal System SO BONE PATHOLOGY, SECOND EDITION LA English DT Article; Book Chapter DE X-rays; Radiogram; CT scan; MRI; CT-guided needle biopsy; Fluoroscopy; Radionuclide imaging; Gallium; Indium; Bone infections; Trauma; Bone tumors; Soft-tissue tumors; Osteoporosis; Fracture Gadolinium-enhanced MRI Angiography; Superscan PET scan; Bone densitometry; Dual energy X-ray absorptiometry (DEXA); QCT; Ultrasound ID SOFT-TISSUE; COMPUTED-TOMOGRAPHY; BONE METASTASES; EWINGS-SARCOMA; RESONANCE; CHEMOTHERAPY; SCINTIGRAPHY; TUMORS; CT; OSTEOMYELITIS AB Modern orthopedic practice relies heavily on various imaging modalities including plain radiographs, computer-assisted tomography, magnetic resonance imaging and bone scintigrams. These techniques help in diagnosis and management of various orthopedic problems such as trauma, tumor, infections and metabolic skeletal diseases. C1 [Reinus, William R.] Temple Univ Hosp & Med Sch, Dept Radiol Planning & Dev, Philadelphia, PA 19140 USA. [Kattapuram, Susan V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Khurana, Jasvir S.] Temple Univ, Sch Med, Dept Pathol, Philadelphia, PA 19140 USA. RP Reinus, WR (reprint author), Temple Univ Hosp & Med Sch, Dept Radiol Planning & Dev, Philadelphia, PA 19140 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-766-2 PY 2009 BP 139 EP 158 DI 10.1007/978-1-59745-347-9_9 D2 10.1007/978-1-59745-347-9 PG 20 WC Orthopedics; Pathology SC Orthopedics; Pathology GA BKU76 UT WOS:000269294500009 ER PT J AU Carlson, NE Brenner, LA Wierman, ME Harrison-Felix, C Morey, C Gallagher, S Ripley, D AF Carlson, N. E. Brenner, L. A. Wierman, M. E. Harrison-Felix, C. Morey, C. Gallagher, S. Ripley, D. TI Hypogonadism on admission to acute rehabilitation is correlated with lower functional status at admission and discharge SO BRAIN INJURY LA English DT Article DE Endocrine dysfunction; physical function; testosterone; traumatic brain injury ID TRAUMATIC BRAIN-INJURY; LOW TESTOSTERONE LEVELS; SEX-HORMONES; HEAD-INJURY; NEUROENDOCRINE DYSFUNCTION; SUBARACHNOID HEMORRHAGE; COGNITIVE FUNCTION; PRACTICAL SCALE; INFECTED MEN; ELDERLY-MEN AB Primary objective: To investigate the association between hormone levels and functional status during acute TBI rehabilitation. Research design: Retrospective cohort study of 43 men with moderate-to-severe TBI admitted to an acute rehabilitation unit during a 1 year period. Methods and procedures: Labs were drawn on admission, including total and free testosterone (T), prolactin, adrenocorticotropin hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (fT4) and insulin-like growth factor (IGF-1). Functional Independence Measure (FIM) scores were obtained at admission and discharge. Main outcome and results: Associations between admission hormone levels and the main outcomes, admission and discharge FIM scores, were assessed using linear regression. Lower total and free T-levels at admission were associated with lower total FIM scores at admission (p 0.038) and discharge (p 0.046). Higher cortisol levels at admission were significantly associated with lower admission (p = 0.012) and discharge (p = 0.036) scores on the cognitive-FIM. Prolactin, TSH, fT4 and IGF-1 were not correlated with functional status. Conclusions: In men, lower total and free T-levels at admission to acute rehabilitation correlate with lower admission and discharge FIM scores. These data support the need for studies to investigate the impact of physiological testosterone therapy on outcomes during and post-rehabilitation. C1 [Carlson, N. E.] Univ Colorado Denver, Dept Biostat & Informat, Aurora, CO 80045 USA. [Brenner, L. A.] VA VISN 19 Mental Illness Res Educ & Clin Ctr, Denver, CO USA. [Brenner, L. A.; Harrison-Felix, C.; Morey, C.; Ripley, D.] Craig Hosp, Rocky Mt Reg Traumat Brain Injury Syst, Englewood, CO USA. [Wierman, M. E.] Univ Colorado, Dept Psychiat, Denver, CO USA. [Brenner, L. A.] Univ Colorado, Dept Neurol, Denver, CO USA. [Brenner, L. A.; Harrison-Felix, C.] Univ Colorado, Dept Phys Med & Rehabil, Denver, CO USA. [Wierman, M. E.] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Wierman, M. E.] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Gallagher, S.] Childrens Hosp, Denver, CO 80218 USA. RP Carlson, NE (reprint author), Univ Colorado Denver, Dept Biostat & Informat, 17000 E 17th PL,MS C245, Aurora, CO 80045 USA. EM nichole.carlson@ucdenver.edu NR 48 TC 15 Z9 15 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PY 2009 VL 23 IS 4 BP 336 EP 344 AR PII 909972518 DI 10.1080/02699050902788535 PG 9 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 425MY UT WOS:000264643000008 PM 19330595 ER PT J AU Saunders, LL Selassie, AW Hill, EG Nicholas, JS Horner, MD Corrigan, JD Lackland, DT AF Saunders, Lee L. Selassie, Anbesaw W. Hill, Elizabeth G. Nicholas, Joyce S. Horner, Michael David Corrigan, John D. Lackland, Daniel T. TI A population-based study of repetitive traumatic brain injury among persons with traumatic brain injury SO BRAIN INJURY LA English DT Article DE Brain injuries; epilepsy; seizures; epidemiology; survival analysis ID PROFESSIONAL FOOTBALL PLAYERS; RECURRENT CONCUSSION; SOCIOECONOMIC-STATUS; UNITED-STATES; HEAD TRAUMA; RATES; HOSPITALIZATION; COLLEGIATE; SEIZURES; OUTCOMES AB Primary objective: The objective was to estimate and compare the hazards of repetitive traumatic brain injury (RTBI) events as a function of the index TBI severity, in a cohort of TBI hospital discharges include in the South Carolina Traumatic Brain Injury Follow-up Registry. Research design: Retrospective cohort. Methods and procedures: There were 4357 persons with TBI who were followed from the index hospital discharge through 31 December 2005 for RTBI events through the statewide hospital discharge (HD) and emergency department (ED) records. Prentice, Williams, Peterson total time/conditional probability model (PWP-CP) for recurrent events survival analysis was used to assess RTBI as a function of index TBI severity. Main outcomes and results: Index TBI severity approached significance in its relationship with RTBI, with persons with a severe index TBI experiencing events at a higher rate than those with a mild/moderate index TBI. Among the other covariates evaluated, epilepsy/seizure disorder, race, gender, payer status, cause of injury and having a prior history of TBI were associated with RTBI. Conclusions: While TBI severity approached significance with RTBI, other variables, such as epilepsy/seizure disorder, seem to have a more significant relationship with RTBI. C1 [Saunders, Lee L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Selassie, Anbesaw W.; Hill, Elizabeth G.; Nicholas, Joyce S.; Lackland, Daniel T.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Horner, Michael David] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Horner, Michael David] Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Corrigan, John D.] Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. RP Saunders, LL (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St,Suite 117,MSC 700, Charleston, SC 29425 USA. EM saundel@musc.edu FU Division of Injury Response, National Center for Injury Prevention and Control (CIPC), Centers for Disease Control and Prevention (CDC) [U17/CCU421926] FX This study was supported by Grant No. U17/CCU421926 from the Division of Injury Response, National Center for Injury Prevention and Control (CIPC), Centers for Disease Control and Prevention (CDC) ( PI: Anbesaw W. Selassie). The study was performed pursuant to a jointly financed cooperative arrangement between the NCPIC, the National Center for Chronic Disease Prevention and Health Promotion, CDC and the Social Security Administration (SSA), Office of Disability Income and Support Programs. The opinions and conclusions expressed are solely the authors' and should not be construed as representing the opinions or policy of CDC, SSA, or any agency of the federal government. NR 33 TC 10 Z9 10 U1 5 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PY 2009 VL 23 IS 11 BP 866 EP 872 AR PII 915242880 DI 10.1080/02699050903283213 PG 7 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 498JY UT WOS:000270137300002 PM 20100122 ER PT J AU Brenner, LA Carlson, NE Harrison-Felix, C Ashman, T Hammond, FM Hirschberg, RE AF Brenner, Lisa A. Carlson, Nichole E. Harrison-Felix, Cynthia Ashman, Teresa Hammond, Flora M. Hirschberg, Ronald E. TI Self-inflicted traumatic brain injury: Characteristics and outcomes SO BRAIN INJURY LA English DT Article DE Traumatic brain injury; suicide; self-inflicted; inpatient rehabilation ID DISABILITY RATING-SCALE; FUNCTIONAL INDEPENDENCE MEASURE; RISK-FACTORS; SUICIDE-PREVENTION; MODEL SYSTEMS; VIOLENCE; POPULATION; VALIDITY; BEHAVIOR AB Objective: To characterize the population of those receiving inpatient rehabilitation who sustained a traumatic brain injury (TBI) secondary to a suicide attempt and identify differences between such individuals and a demographically-matched control group (n = 230) of those whose TBIs were of an unintentional aetiology. Method: Analysed cases were identified from the TBI Model Systems National Database. Based on ICD-9-CM external cause-of-injury codes, 79 participants incurred a TBI secondary to a suicide attempt. An approximate 1 : 3 matched case-control (age, gender, race, injury year) design was chosen to make statistical comparisons. Results: Those who sustained a TBI secondary to a suicide attempt had greater pre-existing psychiatric and psychosocial problems (substance use problems (p = 0.01) prior suicide attempt (p<0.0001), psychiatric hospitalization (p = 0.014) and non-productive activity (p = 0.014)), required more resources during acute and rehabilitative hospitalizations (i.e. charges per day; p = 0.024, p = 0.047) and had greater disability at the time of discharge, even after controlling for injury severity (p = 0.022). Conclusion: Individuals who sustained TBIs secondary to a suicide attempt had increased pre-injury psychiatric and psychosocial problems and poorer outcomes at discharge than those who incurred unintentional injuries. For these individuals, acute and rehabilitation charges per day were higher and could not be accounted for by injury severity. C1 [Brenner, Lisa A.] Denver VAMC, MIRECC, VA VISN 19, Denver, CO 80223 USA. [Brenner, Lisa A.] Univ Colorado Denver, Sch Med, Dept Psychiat, Denver, CO USA. [Brenner, Lisa A.] Univ Colorado Denver, Sch Med, Dept Neurol, Denver, CO USA. [Brenner, Lisa A.; Harrison-Felix, Cynthia] Univ Colorado Denver, Sch Med, Dept Phys Med & Rehabil, Denver, CO USA. [Brenner, Lisa A.; Carlson, Nichole E.; Harrison-Felix, Cynthia] Craig Hosp, Englewood, CO USA. [Carlson, Nichole E.] Univ Colorado Denver, Dept Biostat & Informat, Denver, CO USA. [Ashman, Teresa] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Hammond, Flora M.] Carolinas Traumat Brain Injury Rehabil & Res Syst, Charlotte, NC USA. [Hirschberg, Ronald E.] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Hirschberg, Ronald E.] Spaulding Rehabil Hosp, Boston, MA USA. RP Brenner, LA (reprint author), Denver VAMC, MIRECC, VA VISN 19, 1055 Clermont St, Denver, CO 80223 USA. EM lisa.brenner@va.gov RI Ashman, Teresa/B-1621-2013 NR 30 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PY 2009 VL 23 IS 13-14 BP 991 EP 998 DI 10.3109/02699050903379362 PG 8 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 529YR UT WOS:000272556000001 PM 19891537 ER PT J AU Freeman, SH Hyman, BT Sims, KB Hedley-Whyte, ET Vossough, A Frosch, MP Schmahmann, JD AF Freeman, Stefanie H. Hyman, Bradley T. Sims, Katherine B. Hedley-Whyte, E. T. Vossough, Arastoo Frosch, Matthew P. Schmahmann, Jeremy D. TI Adult Onset Leukodystrophy with Neuroaxonal Spheroids: Clinical, Neuroimaging and Neuropathologic Observations SO BRAIN PATHOLOGY LA English DT Article DE neuroaxonal spheroids; leukodystrophy; hereditary diffuse leukodystrophy; pigmented orthochromic leukodystrophy ID HEREDITARY DIFFUSE LEUKOENCEPHALOPATHY; POSTERIOR PARIETAL CORTEX; RHESUS-MONKEY; AUTOSOMAL-DOMINANT; PIGMENTED GLIA; CORTICOTHALAMIC CONNECTIONS; AXONAL SPHEROIDS; THALAMUS; PROJECTIONS; DEMENTIA AB Pigmented orthochromatic leukodystrophy and hereditary diffuse leukoencephalopathy with spheroids are two adult onset leukodystrophies with neuroaxonal spheroids presenting with prominent neurobehavioral, cognitive and motor symptoms. These are familial or sporadic disorders characterized by cerebral white matter degeneration including myelin and axonal loss, gliosis, macrophages and axonal spheroids. We report clinical, neuroimaging and pathological correlations of four women ages 34-50 years with adult onset leukodystrophy. Their disease course ranged from 1.5-8 years. Three patients had progressive cognitive and behavioral changes; however, one had acute onset. Neuroimaging revealed white matter abnormalities characterized by symmetric, bilateral, T2 hyperintense and T1 hypointense Magnetic Resonance Imaging signal involving frontal lobe white matter in all patients. Extensive laboratory investigations were negative apart from abnormalities in some mitochondrial enzymes and immunologic parameters. Autopsies demonstrated severe leukodystrophy with myelin and axonal loss, axonal spheroids and macrophages with early and severe frontal white matter involvement. The extent and degree of changes outside the frontal lobe appeared to correlate with disease duration. The prominent neurobehavioral deficits and frontal white matter disease provide clinical-pathologic support for association pathways linking distributed neural circuits sub-serving cognition. These observations lend further support to the notion that white matter disease alone can account for dementia. C1 [Freeman, Stefanie H.; Hyman, Bradley T.; Hedley-Whyte, E. T.; Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02115 USA. [Freeman, Stefanie H.; Hyman, Bradley T.; Frosch, Matthew P.] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Boston, MA USA. [Sims, Katherine B.; Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Vossough, Arastoo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Freeman, SH (reprint author), Massachusetts Gen Hosp East, Alzheimer Dis Res Ctr, 2650,114 16th St, Charlestown, MA 02129 USA. EM sfreeman1@partners.org FU Massachusetts Alzheimer Disease Research Center [AG05134] FX Supported by AG05134 (Massachusetts Alzheimer Disease Research Center). NR 34 TC 46 Z9 47 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2009 VL 19 IS 1 BP 39 EP 47 DI 10.1111/j.1750-3639.2008.00163.x PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 379KN UT WOS:000261395200005 PM 18422757 ER PT J AU Garber, JE AF Garber, J. E. TI Identifying and assessing women at high risk for breast cancer SO BREAST CANCER RESEARCH LA English DT Meeting Abstract CT 8th Madrid Breast Cancer Conference CY JUN 24-26, 2009 CL Madrid, SPAIN C1 [Garber, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 SU 1 BP S1 EP S1 DI 10.1186/bcr2262 PG 1 WC Oncology SC Oncology GA 465VZ UT WOS:000267618500002 ER PT J AU Polyak, K Shipitsin, M Campbell-Marrotta, LL Bloushtain-Qimron, N Park, SY AF Polyak, K. Shipitsin, M. Campbell-Marrotta, L. L. Bloushtain-Qimron, N. Park, So Yeon TI Breast tumor heterogeneity: causes and consequences SO BREAST CANCER RESEARCH LA English DT Meeting Abstract CT 8th Madrid Breast Cancer Conference CY JUN 24-26, 2009 CL Madrid, SPAIN C1 [Polyak, K.; Shipitsin, M.; Campbell-Marrotta, L. L.; Bloushtain-Qimron, N.; Park, So Yeon] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 4 TC 10 Z9 10 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 SU 1 BP S8 EP S8 DI 10.1186/bcr2279 PG 1 WC Oncology SC Oncology GA 465VZ UT WOS:000267618500019 ER PT J AU Winer, EP AF Winer, E. P. TI Adjuvant therapy of HER2(+) breast cancer SO BREAST CANCER RESEARCH LA English DT Meeting Abstract CT 8th Madrid Breast Cancer Conference CY JUN 24-26, 2009 CL Madrid, SPAIN C1 [Winer, E. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 SU 1 BP S6 EP S6 DI 10.1186/bcr2274 PG 1 WC Oncology SC Oncology GA 465VZ UT WOS:000267618500014 ER PT J AU Behbod, F Kittrell, FS LaMarca, H Edwards, D Kerbawy, S Heestand, JC Young, E Mukhopadhyay, P Yeh, HW Allred, DC Hu, M Polyak, K Rosen, JM Medina, D AF Behbod, Fariba Kittrell, Frances S. LaMarca, Heather Edwards, David Kerbawy, Sofia Heestand, Jessica C. Young, Evelin Mukhopadhyay, Purna Yeh, Hung-Wen Allred, D. Craig Hu, Min Polyak, Kornelia Rosen, Jeffrey M. Medina, Daniel TI An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ SO BREAST CANCER RESEARCH LA English DT Article ID INVASIVE BREAST-CARCINOMA; BASAL-LIKE SUBTYPE AB Introduction Human models of noninvasive breast tumors are limited, and the existing in vivo models do not mimic inter-and intratumoral heterogeneity. Ductal carcinoma in situ (DCIS) is the most common type (80%) of noninvasive breast lesions. The aim of this study was to develop an in vivo model whereby the natural progression of human DCIS might be reproduced and studied. To accomplish this goal, the intraductal human-in-mouse (HIM) transplantation model was developed. The resulting models, which mimicked some of the diversity of human noninvasive breast cancers in vivo, were used to show whether subtypes of human DCIS might contain distinct subpopulations of tumor-initiating cells. Methods The intraductal models were established by injection of human DCIS cell lines (MCF10DCIS. COM and SUM-225), as well as cells derived from a primary human DCIS (FSK-H7), directly into the primary mouse mammary ducts via cleaved nipple. Six to eight weeks after injections, whole-mount, hematoxylin and eosin, and immunofluorescence staining were performed to evaluate the type and extent of growth of the DCIS-like lesions. To identify tumor-initiating cells, putative human breast stem/progenitor subpopulations were sorted from MCF10DCIS. COM and SUM-225 with flow cytometry, and their in vivo growth fractions were compared with the Fisher's Exact test. Results Human DCIS cells initially grew within the mammary ducts, followed by progression to invasion in some cases into the stroma. The lesions were histologically almost identical to those of clinical human DCIS. This method was successful for growing DCIS cell lines (MCF10DCIS. COM and SUM-225) as well as a primary human DCIS (FSK-H7). MCF10DCIS. COM represented a basal-like DCIS model, whereas SUM-225 and FSK-H7 cells were models for HER-2(+) DCIS. With this approach, we showed that various subtypes of human DCIS appeared to contain distinct subpopulations of tumor-initiating cells. Conclusions The intraductal HIM transplantation model provides an invaluable tool that mimics human breast heterogeneity at the noninvasive stages and allows the study of the distinct molecular and cellular mechanisms of breast cancer progression. C1 [Behbod, Fariba; Kerbawy, Sofia] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. [Kittrell, Frances S.; LaMarca, Heather; Edwards, David; Heestand, Jessica C.; Young, Evelin; Rosen, Jeffrey M.; Medina, Daniel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Mukhopadhyay, Purna; Yeh, Hung-Wen] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66160 USA. [Allred, D. Craig] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA. [Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Behbod, F (reprint author), Univ Kansas, Med Ctr, Dept Pathol & Lab Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM fbehbod@kumc.edu RI Mukhopadhyay, Purna/J-3690-2013 FU NCI [1K99CA127462, 5 P50 CA058183-13 DEV PJ19]; NIH [CA116235]; Susan G Komen Breast Cancer Foundation [PDF042234]; Breast Cancer Research Foundation (BCRF) FX The authors thank Drs. Sue Hilsenbeck (Baylor College of Medicine), Charlotte Kuperwasser (Tufts University School of Medicine), Connie Eaves (Terry Fox Laboratory), Charles M. Perou, (University of North Carolina), and Alejandro Contreras (Baylor College of Medicine) for their helpful suggestions, contributions to data analysis, and guidance on the project. The authors also thank Joel Sedestrom and Candice Seller (Baylor College of Medicine Flow Core) for their assistance with the flow-cytometry analysis and cell sorting. This work was supported by NCI (1K99CA127462) and 5 P50 CA058183-13 DEV PJ19 to FB, NIH (CA116235) awarded to KP, Susan G Komen Breast Cancer Foundation (PDF042234) to MH, and the Breast Cancer Research Foundation (BCRF) to DCA. NR 11 TC 64 Z9 65 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 5 AR R66 DI 10.1186/bcr2358 PG 11 WC Oncology SC Oncology GA 540OD UT WOS:000273342300011 PM 19735549 ER PT J AU Gonzalez, RR Watters, A Xu, YB Singh, UP Mann, DR Rueda, BR Penichet, ML AF Gonzalez, Ruben Rene Watters, Amber Xu, Yanbo Singh, Udai P. Mann, David R. Rueda, Bo R. Penichet, Manuel L. TI Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-I; ENDOMETRIAL CELLS; MAMMARY-TUMORS; BCL-2 EXPRESSION; FEMALE MICE; CYCLIN D1; ALPHA; RISK; TRANSACTIVATION; PREMENOPAUSAL AB Introduction We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER(+)) and estrogen receptor-negative (ER(-)) BC xenografts hosted by immunodeficient mice. Methods To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER(+) (MCF-7 cells; ovariectomized/ supplemented with estradiol) and ER(-) (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER(+) and ER(-) BC, the expression of VEGF and VEGFR2 ( protein and mRNA) was investigated in cell cultures. Results PEG-LPrA2 more effectively reduced the growth of ER(+) (> 40-fold) than ER(-) BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D(1)) in ER(+) than in ER(-) BC. Mouse tumor stroma in ER(+) BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells. Conclusions These results suggest that leptin signaling plays an important role in the growth of both ER(+) and ER(-) BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER(+) and ER(-) BC. C1 [Gonzalez, Ruben Rene; Watters, Amber; Xu, Yanbo] Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. [Gonzalez, Ruben Rene; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Gonzalez, Ruben Rene] Boston Biomed Res Inst, Watertown, MA 02472 USA. [Singh, Udai P.] Univ S Carolina, Dept Pathol Microbiol & Immunol, Sch Med, Columbia, SC 29208 USA. [Mann, David R.] Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA. [Rueda, Bo R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Penichet, Manuel L.] Univ Calif Los Angeles, David Geffen Sch Med, Jonnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Penichet, Manuel L.] Univ Calif Los Angeles, Dept Surg, Div Surg Oncol, Los Angeles, CA 90095 USA. RP Gonzalez, RR (reprint author), Morehouse Sch Med, Dept Microbiol Biochem & Immunol, 720 Westview Dr SW, Atlanta, GA 30310 USA. EM rgonzalez@msm.edu FU NIH/NCI [5SC1CA138658-01]; NIH/UAB Breast SPORE Career Development Award [BC 504370]; Susan G. Komen Foundation for the Cure; Cancer Research and Prevention Foundation; Georgia Cancer Coalition Distinguished Cancer Scholar Award [CIG-07-114]; Consortium for Industrial Collaboration in Contraceptive Research (CICCR); Contraceptive Research and Development Program (CONRAD); Eastern Virginia Medical School; NIH/HD [41749]; Morehouse School of Medicine Dean's Fund for Minority Student Training [NIH RR03034, 1C06 RR18386] FX Funding awarded to RRG includes NIH/NCI 5SC1CA138658-01, NIH/UAB Breast SPORE Career Development Award, BC 504370 Susan G. Komen Foundation for the Cure, the Cancer Research and Prevention Foundation, the Georgia Cancer Coalition Distinguished Cancer Scholar Award, CIG-07-114 Consortium for Industrial Collaboration in Contraceptive Research (CICCR), and Contraceptive Research and Development Program (CONRAD), Eastern Virginia Medical School. Funding awarded to DRM includes NIH/HD41749. Other funds were from the Morehouse School of Medicine Dean's Fund for Minority Student Training, facilities and support services at Morehouse School of Medicine (NIH RR03034 and 1C06 RR18386). NR 48 TC 69 Z9 69 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 3 AR R36 DI 10.1186/bcr2321 PG 12 WC Oncology SC Oncology GA 487WS UT WOS:000269309200017 ER PT J AU Heckman-Stoddard, BM Vargo-Gogola, T McHenry, PR Jiang, V Herrick, MP Hilsenbeck, SG Settleman, J Rosen, JM AF Heckman-Stoddard, Brandy M. Vargo-Gogola, Tracy McHenry, Peter R. Jiang, Vivian Herrick, Matthew P. Hilsenbeck, Susan G. Settleman, Jeffrey Rosen, Jeffrey M. TI Haploinsufficiency for p190B RhoGAP inhibits MMTV-Neu tumor progression SO BREAST CANCER RESEARCH LA English DT Article ID HUMAN-BREAST-CANCER; GTPASE-ACTIVATING PROTEIN; TRANSGENIC MICE; DUCTAL MORPHOGENESIS; ANGIOGENIC SWITCH; MAMMARY-GLAND; GROWTH-FACTOR; CELL; EXPRESSION; OVEREXPRESSION AB Introduction Rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. P190B Rho GTPase activating protein (RhoGAP) functions as a major inhibitor of the Rho GTPases. P190B is required for mammary gland morphogenesis, and overexpression of p190B in the mammary gland induces hyperplastic lesions. Hence, we hypothesized that p190B may play a pivotal role in mammary tumorigenesis. Methods To investigate the effects of loss of p190B function on mammary tumor progression, p190B heterozygous mice were crossed with an MMTV-Neu breast cancer model. Effects of p190B deficiency on tumor latency, multiplicity, growth, preneoplastic progression and metastasis were evaluated. To investigate potential differences in tumor angiogenesis between the two groups, immunohistochemistry to detect von Willebrand factor was performed and quantified. To examine gene expression of potential mediators of the angiogenic switch, an angiogenesis PCR array was utilized and results were confirmed using immunohistochemistry. Finally, reciprocal transplantation of tumor fragments was performed to determine the impact of stromal deficiency of p190B on tumor angiogenesis. Results P190B deficiency reduced tumor penetrance (53% of p190B(+/-)Neu mice vs. 100% of p190B(+/+)Neu mice formed tumors) and markedly delayed tumor onset by an average of 46 weeks. Tumor multiplicity was also decreased, but an increase in the number of preneoplastic lesions was detected indicating that p190B deficiency inhibited preneoplastic progression. Angiogenesis was decreased in the p190B heterozygous tumors, and expression of a potent angiogenic inhibitor, thrombospondin-1, was elevated in p190B(+/-)Neu mammary glands. Transplantation of p190B(+/-)Neu tumor fragments into wild-type recipients restored tumor angiogenesis. Strikingly, p190B(+/+)Neu tumor fragments were unable to grow when transplanted into p190B(+/-)Neu recipients. Conclusions These data suggest that p190B haploinsufficiency in the epithelium inhibits MMTV-Neu tumor initiation. Furthermore, p190B deficiency in the vasculature is responsible, in part, for the inhibition of MMTV-Neu tumor progression. C1 [Heckman-Stoddard, Brandy M.; Jiang, Vivian; Herrick, Matthew P.; Rosen, Jeffrey M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Heckman-Stoddard, Brandy M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD 20852 USA. [Vargo-Gogola, Tracy; McHenry, Peter R.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, South Bend, IN 46617 USA. [Hilsenbeck, Susan G.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Hilsenbeck, Susan G.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM jrosen@bcm.edu FU DOD [W81XWH-06-1-0704]; [CA030195-22]; [K99CA127361] FX These studies were supported through grant CA030195-22. TV-G is funded by K99CA127361. BMH-S was funded by DOD predoctoral fellowship W81XWH-06-1-0704 and is currently a NCI Cancer Prevention Fellow. The authors thank Shirley Small for her help with animal husbandry and colony management, and Maria Gonzalez-Rimbau for technical support. NR 37 TC 11 Z9 11 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 4 AR R61 DI 10.1186/bcr2352 PG 12 WC Oncology SC Oncology GA 514RT UT WOS:000271414000024 PM 19703301 ER PT J AU Ma, XJ Dahiya, S Richardson, E Erlander, M Sgroi, DC AF Ma, Xiao-Jun Dahiya, Sonika Richardson, Elizabeth Erlander, Mark Sgroi, Dennis C. TI Gene expression profiling of the tumor microenvironment during breast cancer progression SO BREAST CANCER RESEARCH LA English DT Article ID SET ENRICHMENT ANALYSIS; STROMAL CELLS; IN-SITU; IMMUNE-SYSTEM; WNT PATHWAY; CARCINOMAS; PROLIFERATION; METASTASIS; TRANSITION; RECEPTORS AB Introduction The importance of the tumor microenvironment in breast cancer has been increasingly recognized. Critical molecular changes in the tumor stroma accompanying cancer progression, however, remain largely unknown. We conducted a comparative analysis of global gene expression changes in the stromal and epithelial compartments during breast cancer progression from normal to preinvasive to invasive ductal carcinoma. Methods We combined laser capture microdissection and gene expression microarrays to analyze 14 patient-matched normal epithelium, normal stroma, tumor epithelium and tumor-associated stroma specimens. Differential gene expression and gene ontology analyses were performed. Results Tumor-associated stroma undergoes extensive gene expression changes during cancer progression, to a similar extent as that seen in the malignant epithelium. Highly upregulated genes in the tumor-associated stroma include constituents of the extracellular matrix and matrix metalloproteases, and cell-cycle-related genes. Decreased expression of cytoplasmic ribosomal proteins and increased expression of mitochondrial ribosomal proteins were observed in both the tumor epithelium and the stroma. The transition from preinvasive to invasive growth was accompanied by increased expression of several matrix metalloproteases (MMP2, MMP11 and MMP14). Furthermore, as observed in malignant epithelium, a gene expression signature of histological tumor grade also exists in the stroma, with high-grade tumors associated with increased expression of genes involved in immune response. Conclusions Our results suggest that the tumor microenvironment participates in tumorigenesis even before tumor cells invade into stroma, and that it may play important roles in the transition from preinvasive to invasive growth. The immune cells in the tumor stroma may be exploited by the malignant epithelial cells in high-grade tumors for aggressive invasive growth. C1 [Dahiya, Sonika; Richardson, Elizabeth; Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Dahiya, Sonika; Richardson, Elizabeth; Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Ma, Xiao-Jun; Erlander, Mark] bioTheranostics Inc, San Diego, CA 92121 USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149 13th St, Charlestown, MA 02129 USA. EM dsgroi@partners.org FU NIH [RO1-1CA112021-01]; Department of Defense [W81XWH-04-1-0606, DAMD170310428]; Susan G. Komen Breast Cancer Foundation [BCTR0402932]; Avon Foundation FX The present study was supported by NIH RO1-1CA112021-01 ( to DCS), the Department of Defense grants W81XWH-04-1-0606 and DAMD170310428 ( to DCS), Susan G. Komen Breast Cancer Foundation grant BCTR0402932 ( to DCS), and the Avon Foundation ( to DCS). The authors thank Erica Chatfield for technical assistance in microdissection and RNA extraction, and they thank Sridhar Ramaswamy and E. Schmidt for helpful discussions and reading of the manuscript. NR 53 TC 222 Z9 227 U1 3 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 1 AR R7 DI 10.1186/bcr2222 PG 18 WC Oncology SC Oncology GA 448LY UT WOS:000266265300011 PM 19187537 ER PT J AU Neuhausen, SL Brummel, S Ding, YC Singer, CF Pfeiler, G Lynch, HT Nathanson, KL Rebbeck, TR Garber, JE Couch, F Weitzel, J Narod, SA Ganz, PA Daly, MB Godwin, AK Isaacs, C Olopade, OI Tomlinson, G Rubinstein, WS Tung, N Blum, JL Gillen, DL AF Neuhausen, Susan L. Brummel, Sean Ding, Yuan Chun Singer, Christian F. Pfeiler, Georg Lynch, Henry T. Nathanson, Katherine L. Rebbeck, Timothy R. Garber, Judy E. Couch, Fergus Weitzel, Jeffrey Narod, Steven A. Ganz, Patricia A. Daly, Mary B. Godwin, Andrew K. Isaacs, Claudine Olopade, Olufunmilayo I. Tomlinson, Gail Rubinstein, Wendy S. Tung, Nadine Blum, Joanne L. Gillen, Daniel L. TI Genetic variation in insulin-like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers SO BREAST CANCER RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; BINDING PROTEIN-5 IGFBP-5; MUTATION CARRIERS; FACTOR-I; MULTIETHNIC COHORT; OVARIAN-CANCER; MAMMOGRAPHIC DENSITY; THERAPEUTIC TARGET; CIRCULATING LEVELS; COMMON VARIANTS AB Introduction Women who carry mutations in BRCA1 and BRCA2 have a substantially increased risk of developing breast cancer as compared with the general population. However, risk estimates range from 20 to 80%, suggesting the presence of genetic and/or environmental risk modifiers. Based on extensive in vivo and in vitro studies, one important pathway for breast cancer pathogenesis may be the insulin-like growth factor (IGF) signaling pathway, which regulates both cellular proliferation and apoptosis. BRCA1 has been shown to directly interact with IGF signaling such that variants in this pathway may modify risk of cancer in women carrying BRCA mutations. In this study, we investigate the association of variants in genes involved in IGF signaling and risk of breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations. Methods A cohort of 1,665 adult, female mutation carriers, including 1,122 BRCA1 carriers (433 cases) and 543 BRCA2 carriers (238 cases) were genotyped for SNPs in IGF1, IGF1 receptor (IGF1R), IGF1 binding protein (IGFBP1, IGFBP2, IGFBP5), and IGF receptor substrate 1 (IRS1). Cox proportional hazards regression was used to model time from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately. For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic model was assumed; and for single SNP analyses, no additivity assumptions were made. Results Among BRCA1 carriers, significant associations were found between risk of breast cancer and LD blocks in IGF1R (global P = 0.011 for LD block 2 and global P = 0.012 for LD block 11). Among BRCA2 carriers, an LD block in IGFBP2 (global P = 0.0145) was found to be associated with the time to breast cancer diagnosis. No significant LD block associations were found for the other investigated genes among BRCA1 and BRCA2 carriers. Conclusions This is the first study to investigate the role of genetic variation in IGF signaling and breast cancer risk in women carrying deleterious mutations in BRCA1 and BRCA2. We identified significant associations in variants in IGF1R and IRS1 in BRCA1 carriers and in IGFBP2 in BRCA2 carriers. Although there is known to be interaction of BRCA1 and IGF signaling, further replication and identification of causal mechanisms are needed to better understand these associations. C1 [Neuhausen, Susan L.; Ding, Yuan Chun; Gillen, Daniel L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA. [Brummel, Sean; Gillen, Daniel L.] Univ Calif Irvine, Dept Stat, Irvine, CA 92697 USA. [Singer, Christian F.; Pfeiler, Georg] Med Univ Vienna, Div Special Gynecol, Dept Obstet & Gynaecol, A-1090 Vienna, Austria. [Lynch, Henry T.] Creighton Univ, Dept Prevent Med & Publ Hlth, Sch Med, Omaha, NE 68182 USA. [Nathanson, Katherine L.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Garber, Judy E.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Couch, Fergus] Mayo Clin, Mayo Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Weitzel, Jeffrey] City Hope Natl Med Ctr, Dept Populat Sci, Div Clin Canc Genet, Duarte, CA 91010 USA. [Narod, Steven A.] Womens Coll Hosp, Womens Coll, Res Inst, Toronto, ON M5G 1N8, Canada. [Ganz, Patricia A.] UCLA Sch Med, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. [Ganz, Patricia A.] UCLA Sch Publ Hlth, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA. [Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Isaacs, Claudine] Georgetown Univ, Dept Med & Oncol, Washington, DC 20007 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Tomlinson, Gail] Univ Texas Hlth Sci Ctr San Antonio, Div Pediat Hematol Oncol, San Antonio, TX 78229 USA. [Rubinstein, Wendy S.] NorthShore Univ Hlth Syst, Dept Med, Evanston, IL 60201 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Blum, Joanne L.] Baylor Univ, Dept Oncol, Med Ctr, Dallas, TX 75246 USA. RP Neuhausen, SL (reprint author), Univ Calif Irvine, Dept Epidemiol, 224 Irvine Hall, Irvine, CA 92697 USA. EM sneuhaus@uci.edu OI Nathanson, Katherine/0000-0002-6740-0901 FU Nebraska Department of Health and Human Services; NIH [5UO1 CA86389, R01-CA083855, R01-CA74415, R01-CA102776, P50CA83638, 5U01CA113916, U01CA69631] FX The Modifiers and Genetics in Cancer Consortium includes the following centers and individuals: Baylor-Charles A. Sammons Cancer Center (Joanne L Blum, Becky Althaus, Gaby Ethington), Beth Israel Deaconess Medical Center (Nadine Tung), City of Hope National Medical Center (Veronica Lagos, Jeffery Weitzel), Creighton University (Carrie Snyder, Henry T Lynch, Patrice Watson), Dana Farber Cancer Institute (Kathryn Stoeckert, Judy E Garber), Northshore University Health System for Medical Genetics (Suzanne M O'Neill, Christina Selkirk, Wendy S Rubinstein), Fox Chase Cancer Center (Mary B Daly, Andrew K Godwin), Georgetown University (Claudine Isaacs), Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (Joyce Seldon, Patricia A Ganz), Mayo Clinic College of Medicine (Linda Wadum, Fergus Couch), University of Chicago (Shelly Cummings, Olufunmilayo Olopade), University of California, Irvine (Susan L Neuhausen, Linda Steele), University of Pennsylvania Health System (Susan Domchek, Katherine Nathanson Tara Friebel, Timothy Rebbeck), University of Texas, San Antonio (Gail Tomlinson), University of Vienna (Christian Singer), and Women's College Hospital (Steven A Narod). This publication was supported in part by revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. The article's contents are solely the responsibility of the authors and do not necessarily represent the official views of the State of Nebraska or the Nebraska Department of Health and Human Services. Support was also received from NIH grants 5UO1 CA86389 (to HTL), R01-CA083855, R01-CA74415 (to SLN), R01-CA102776, R01-CA083855 (to TRR), P50CA83638, 5U01CA113916 (to AKG), and U01CA69631 (to MBD). NR 53 TC 27 Z9 27 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 5 AR R76 DI 10.1186/bcr2414 PG 12 WC Oncology SC Oncology GA 540OD UT WOS:000273342300021 PM 19843326 ER PT J AU Thurlimann, B Price, K Gelber, R Holmberg, S Crivellari, D Colleoni, M Collins, J Forbes, J Castiglione-Gertsch, M Coates, A Goldhirsch, A AF Thuerlimann, Beat Price, Karen N. Gelber, Richard D. Holmberg, Stig B. Crivellari, Diana Colleoni, Marco Collins, John Forbes, John F. Castiglione-Gertsch, Monica Coates, Alan S. Goldhirsch, Aron TI Is chemotherapy necessary for premenopausal women with lower-risk node-positive, endocrine responsive breast cancer? 10-year update of International Breast Cancer Study Group Trial 11-93 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Estrogen receptor; Goserelin; Ovarian ablation; Ovarian function suppression; Tamoxifen ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIALS; THERAPY; TAMOXIFEN AB Introduction International Breast Cancer Study Group (IBCSG) Trial 11-93 is the largest trial evaluating the role of the addition of chemotherapy to ovarian function suppression/ablation (OFS) and tamoxifen in premenopausal patients with endocrine-responsive early breast cancer. Methods IBCSG Trial 11-93 is a randomized trial comparing four cycles of adjuvant chemotherapy (AC: doxorubicin or epirubicin, plus cyclophosphamide) added to OFS and 5 years of tamoxifen versus OFS and tamoxifen without chemotherapy in premenopausal patients with node-positive, endocrine-responsive early breast cancer. There were 174 patients randomized from May 1993 to November 1998. The trial was closed before the target accrual was reached due to low accrual rate. Results Patients randomized tended to have lower risk node-positive disease and the median age was 45. After 10 years median follow up, there remains no difference between the two randomized treatment groups for disease-free (hazard ratio = 1.02 (0.57-1.83); P = 0.94) or overall survival (hazard ratio = 0.97 (0.44-2.16); P = 0.94). Conclusion This trial, although small, offers no evidence that AC chemotherapy provides additional disease control for premenopausal patients with lower-risk node-positive endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy. A large trial is needed to determine whether chemotherapy adds benefit to endocrine therapy for this population. C1 [Thuerlimann, Beat] Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, IBCSG Stat Ctr, Boston, MA USA. [Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA USA. [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Holmberg, Stig B.] Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden. [Crivellari, Diana] Ctr Riferimento Oncol, I-33081 Aviano, Italy. [Colleoni, Marco; Goldhirsch, Aron] European Inst Oncol, Dept Med, Milan, Italy. [Collins, John] Royal Melbourne Hosp, Dept Surg, Parkville, Vic 3050, Australia. [Forbes, John F.] Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. [Castiglione-Gertsch, Monica] IBCSG Coordinating Ctr, CH-3008 Bern, Switzerland. [Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Thurlimann, B (reprint author), Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. EM beat.thuerlimann@kssg.ch; price@jimmy.harvard.edu; gelber@jimmy.harvard.edu; stig.holmberge@vgregion.se; dcrivellari@cro.it; marco.colleoni@ieo.it; johncol@bigpond.net.au; john.forbes@anzbctg.newcastle.edu.au; monica.castiglione@ibcsg.org; alan.coates@ibcsg.org; aron.goldhirsch@ibcsg.org OI Hultborn, Ragnar/0000-0002-4289-9339 FU NCI NIH HHS [CA-75362, U24 CA075362, U24 CA075362-12] NR 19 TC 37 Z9 38 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2009 VL 113 IS 1 BP 137 EP 144 DI 10.1007/s10549-008-9912-9 PG 8 WC Oncology SC Oncology GA 387KM UT WOS:000261951100016 PM 18259856 ER PT J AU Krop, IE Winer, EP AF Krop, Ian E. Winer, Eric P. TI Ten years of HER2-directed therapy: still questions after all these years SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Editorial Material ID HER2-POSITIVE BREAST-CANCER; ADJUVANT CHEMOTHERAPY; PHASE-I; TRASTUZUMAB; PLUS; ANTIBODY; HER2 C1 [Krop, Ian E.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Ian_Krop@dfci.harvard.edu NR 10 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2009 VL 113 IS 2 BP 207 EP 209 DI 10.1007/s10549-008-0041-2 PG 3 WC Oncology SC Oncology GA 391KV UT WOS:000262233100002 PM 18463974 ER PT J AU Martin, SE Sausen, M Joseph, A Biggs, DD Kingham, BF Martin, ES AF Martin, S. Eric Sausen, Mark Joseph, Abraham Biggs, David D. Kingham, Brewster F. Martin, Eric S. TI BRCA1 E1644X: a deleterious mutation in an African American individual with early onset breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE African American; BRCA1 E1644X; Deleterious; Early onset breast cancer; Mutation ID SUSCEPTIBILITY GENE; CANDIDATE; CARRIERS; WOMEN AB An African American individual with early onset breast cancer has a unique BRCA1 germline mutation, E1644X, that truncates the protein's carboxy terminal region. DNA sequencing for E1644X mutation and five BRCA1 exon-11 single nucleotide polymorphisms showed tumor LOH. Clinical history suggests paternal transmission of the deleterious allele, and tumor polymorphisms provide some insight into the ancestral origins of the mutation. C1 [Martin, S. Eric; Biggs, David D.] Helen F Graham Canc Ctr, Newark, DE 19713 USA. [Martin, S. Eric; Biggs, David D.] Christiana Care, Dept Med, Newark, DE USA. [Martin, S. Eric; Joseph, Abraham] Christiana Care, Dept Pathol & Lab Med, Newark, DE USA. [Sausen, Mark] Univ Delaware, Dept Biol Sci, Newark, DE USA. [Kingham, Brewster F.] Univ Delaware, Sequencing & Genotyping Ctr, Newark, DE USA. [Martin, S. Eric] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Martin, S. Eric] Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA USA. RP Martin, SE (reprint author), Helen F Graham Canc Ctr, 4701 Ogletown Stanton Rd,Suite 2200, Newark, DE 19713 USA. EM semartin@cbg.org NR 14 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2009 VL 113 IS 2 BP 393 EP 395 DI 10.1007/s10549-008-9928-1 PG 3 WC Oncology SC Oncology GA 391KV UT WOS:000262233100022 PM 18311584 ER PT J AU Han, TH Martyn, JAJ AF Han, T. -H. Martyn, J. A. J. TI Onset and effectiveness of rocuronium for rapid onset of paralysis in patients with major burns: priming or large bolus SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE burns; neuromuscular block, rocuronium ID ACUTE THERMAL-INJURY; ACETYLCHOLINE-RECEPTORS; NEUROMUSCULAR BLOCKADE; PHARMACODYNAMICS; SUCCINYLCHOLINE; ATRACURIUM AB Background: Burn injury leads to resistance to the effects of non-depolarizing muscle relaxants. We tested the hypothesis that a larger bolus dose is as effective as priming for rapid onset of paralysis after burns. Methods: Ninety adults, aged 1859 yr with 40 (2)% [mean (SE)] burn and 30 (2) days after injury, received rocuronium as a priming dose followed by bolus (0.06+0.94 mg kg(-1)), or single bolus of either 1.0 or 1.5 mg kg(-1). Sixty-one non-burned, receiving 1.0 mg kg(-1) as a primed (0.06+0.94 mg kg(-1)) or full bolus dose, served as controls. Acceleromyography measured the onset times. Results: Priming when compared with 1.0 mg kg(-1) bolus in burned patients shortened the time to first appearance of twitch depression (30 vs 45 s, P<0.05) and time to maximum twitch inhibition (135 vs 210 s, P<0.05). The onset times between priming and higher bolus dose (1.5 mg kg(-1)) were not different (30 vs 30 s for first twitch depression and 135 vs 135 s for maximal depression, respectively). The onset times in controls, however, were significantly (P<0.05) faster than burns both for priming and for full bolus (15 and 15 s, respectively, for first twitch depression and 75 and 75 s for maximal depression). Priming caused respiratory distress in 10% of patients in both groups. Intubating conditions in burns were significantly better with 1.5 mg kg(-1) than with priming or full 1.0 mg kg(-1) bolus. Conclusions: A dose of 1.5 mg kg(-1) not only produces an initial onset of paralysis as early as 30 s, which we speculate could be a reasonable onset time for relief of laryngospasm, but also has an onset as fast as priming with superior intubating conditions and no respiratory side-effects. C1 [Han, T. -H.] Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia, Iowa City, IA 52242 USA. [Martyn, J. A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Martyn, J. A. J.] Shriners Hosp Children, Boston, MA 02114 USA. RP Han, TH (reprint author), Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia, 5937 JPP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM anthony-han@uiowa.edu FU National Institute of Health [R01 GM 31569, RO1 GM 05882, GM 2500-Project IV]; Shriners Hospital Philanthropy FX Supported in part by grants from the National Institute of Health (R01 GM 31569, RO1 GM 05882, and GM 2500-Project IV) and Shriners Hospital Philanthropy ( to J.A.J.M.). NR 21 TC 10 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JAN PY 2009 VL 102 IS 1 BP 55 EP 60 DI 10.1093/bja/aen332 PG 6 WC Anesthesiology SC Anesthesiology GA 380HS UT WOS:000261457400008 PM 19029093 ER PT J AU Becker, ML Visser, LE Newton-Cheh, C Hofman, A Uitterlinden, AG Witteman, JCM Stricker, BHC AF Becker, Matthijs L. Visser, Loes E. Newton-Cheh, Christopher Hofman, Albert Uitterlinden, Andre G. Witteman, Jacqueline C. M. Stricker, Bruno H. Ch. TI A common NOS1AP genetic polymorphism is associated with increased cardiovascular mortality in users of dihydropyridine calcium channel blockers SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE calcium channel blockers; nitric oxide synthase; pharmacogenetics ID NITRIC-OXIDE SYNTHASE; ACUTE MYOCARDIAL-INFARCTION; PROLONGED QTC INTERVAL; CARDIAC REPOLARIZATION; VENTRICULAR MYOCYTES; CA2+ CURRENT; ROTTERDAM; NIFEDIPINE; CONTRACTILITY; ACTIVATION AB WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Neuronal nitric oxide synthase (nNOS) regulates intracellular calcium handling center dot A polymorphism in the NOS1AP gene (rs10494366), a regulator of nNOS, is associated with QTc prolongation center dot Calcium channel blockers also affect calcium handling by blocking the L-type calcium channel WHAT THIS STUDY ADDS center dot We assessed the association between the polymorphism rs10494366 in the NOS1AP gene and mortality in calcium channel blocker users center dot The TG and GG genotype are associated with increased cardiovascular mortality in dihydropyridine calcium channel blocker users Recently, a polymorphism in the NOS1AP gene (rs10494366), a regulator of neuronal nitric oxide synthase (nNOS), was associated with QTc prolongation. Both nNOS and calcium channel blockers (CCBs) regulate intracellular calcium levels and have an important role in cardiovascular homeostasis. The aim was to investigate whether this polymorphism is associated with cardiovascular mortality in users of CCBs. The data from the Rotterdam study, a population-based closed cohort study of Caucasian individuals of >= 55 years of age, were used. We identified 1113 participants in the Rotterdam Study who were prescribed CCBs for the first time between 1991 and 2005. All-cause and cardiovascular mortality was assessed in participants who were prescribed CCBs with different NOS1AP rs10494366 genotypes using Cox proportional hazard models. In participants starting on dihydropyridine CCBs (amlodipine, nifedipine and others) all-cause mortality (n = 79) risks were higher in participants with the TG [hazard ratio (HR) 2.57, 95% confidence interval (CI) 1.24, 5.34] or the GG genotype (HR 3.18, 95% CI 1.18, 8.58) than in participants with the referent TT genotype. Cardiovascular mortality (n = 54) risks were 3.51 (95% CI 1.41, 8.78) for the TG genotype and 6.00 (95% CI 1.80, 20.0) for the GG genotype. No differences in all-cause mortality or cardiovascular mortality were seen in participants starting with the nondihydropyridine CCBs verapamil or diltiazem. The minor G allele of rs10494366 in the NOS1AP gene is associated with increased all-cause and cardiovascular mortality in Caucasian users of dihydropyridine CCBs. The mechanism underlying the observed association is unknown. C1 [Becker, Matthijs L.; Visser, Loes E.; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Epidemiol & Biostat, NL-3000 CA Rotterdam, Netherlands. [Becker, Matthijs L.; Visser, Loes E.] Erasmus MC, Dept Hosp Pharm, NL-3000 CA Rotterdam, Netherlands. [Uitterlinden, Andre G.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Stricker, Bruno H. Ch.] Inspectorate Hlth Care, Drug Safety Unit, The Hague, Netherlands. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. [Newton-Cheh, Christopher] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol & Biostat, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl RI Becker, Matthijs/A-6437-2012 FU Erasmus Medical Centre and Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry of Health, Welfare and Sports; European Commission; Municipality of Rotterdam FX The Rotterdam Study is supported by the Erasmus Medical Centre and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors thank the people in the Rotterdam Study for their participation and Pascal P. Arp for his help with genotyping. NR 28 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD JAN PY 2009 VL 67 IS 1 BP 61 EP 67 DI 10.1111/j.1365-2125.2008.03325.x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 406NU UT WOS:000263303000008 PM 19076153 ER PT J AU Ruddy, K Mayer, E Partridge, A AF Ruddy, Kathryn Mayer, Erica Partridge, Ann TI Patient Adherence and Persistence With Oral Anticancer Treatment SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID POSITIVE BREAST-CANCER; DRUG-THERAPY; TAMOXIFEN THERAPY; CLINICAL-TRIALS; OLDER WOMEN; LYMPHOBLASTIC-LEUKEMIA; ADJUVANT CHEMOTHERAPY; MEDICATION COMPLIANCE; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL AB Given the recent significant increase in the use of oral therapies in cancer-management, an understanding of patients' adherence to and persistence with oral therapy is crucial. Nonadherence and early cessation may be substantial barriers to the delivery of valuable therapies, and may impair health. Potential obstacles to adherence and persistence include personal characteristics, treatment features, and system factors. Techniques for measuring adherence and persistence include self report, pill counts, microelectronic monitoring systems (MEMS), prescription database analysis, and the assessment of serum or urine drug levels. This review article describes available data regarding adherence and persistence among patients with cancer, as well as studies of interventions to improve adherence. All reports of studies of adherence with oral cancer therapy that the authors could find on PubMed or in the reference sections of these PubMed-located articles were included. Adherence and persistence rates ranged from 16% to 100% with different therapies and different methods of Measurement. Studies that included educational, behavioral, and multidimensional interventions to improve adherence were also described. CA Cancer J Clin 2009;59:56-66. (C) 2009.American Cancer-Society. C1 [Ruddy, Kathryn] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Breast Oncol, Boston, MA 02115 USA. RP Ruddy, K (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Breast Oncol, Mayer 215,44 Binney St, Boston, MA 02115 USA. EM kruddy@partners.org NR 79 TC 211 Z9 224 U1 0 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JAN-FEB PY 2009 VL 59 IS 1 BP 56 EP 66 DI 10.3322/caac.20004 PG 11 WC Oncology SC Oncology GA 408PQ UT WOS:000263447500007 PM 19147869 ER PT S AU Bergwitz, C Juppner, H AF Bergwitz, Clemens Jueppner, Harald BE Allgrove, J Shaw, N TI Disorders of Phosphate Homeostasis and Tissue Mineralisation SO CALCIUM AND BONE DISORDERS IN CHILDREN AND ADOLESCENTS SE Endocrine Development LA English DT Article; Book Chapter ID FAMILIAL TUMORAL CALCINOSIS; X-LINKED HYPOPHOSPHATEMIA; FIBROBLAST GROWTH FACTOR-23; HYPEROSTOSIS-HYPERPHOSPHATEMIA SYNDROME; NEVUS-SEBACEOUS-SYNDROME; CHRONIC KIDNEY-DISEASE; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; RESECTION-RELATED HYPOPHOSPHATEMIA; PULMONARY ALVEOLAR MICROLITHIASIS; HOMOZYGOUS MISSENSE MUTATION AB Phosphate is absorbed from the diet in the gut, stored as hydroxyapatite in the skeleton, and excreted with the urine. The balance between these compartments determines the circulating phosphate concentration. Fibroblast growth factor 23 (FGF23) has recently been discovered and is part of a previously unrecognised hormonal bone-kidney axis. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome, and dentin matrix protein 1 regulate the expression of FGF23 in osteocytes, which then is O-glycosylated by UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl-transferase 3 and secreted into the circulation. FGF23 binds with high affinity to fibroblast growth factor receptor I c in the presence of its co-receptor Klotho. It inhibits, either directly or indirectly, reabsorption of phosphate and the synthesis of 1,25-dihydroxy-vitamin-D by the renal proximal tubule and the secretion of parathyroid hormone by the parathyroid glands. Acquired or inborn errors affecting this newly discovered hormonal system can lead to abnormal phosphate homeostasis and/or tissue mineralisation. This chapter will provide an update on the current knowledge of the pathophysiology, the clinical presentation, diagnostic evaluation and therapy of the disorders of phosphate homeostasis and tissue mineralisation. Copyright (C) 2009 S. Karger AG, Basel C1 [Bergwitz, Clemens] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Unit, Boston, MA 02114 USA. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM cbergwitz@partners.org FU NIDDK NIH HHS [K08 DK078361, P01 DK011794, R03 DK089127] NR 140 TC 16 Z9 16 U1 0 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-7082 BN 978-3-8055-9161-4 J9 ENDOCR DEV JI Endocr. Dev. PY 2009 VL 16 BP 133 EP 156 PG 24 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BKK50 UT WOS:000268387400009 PM 19494665 ER PT J AU Goldhaber-Fiebert, SN Goldhaber-Fiebert, JD Rosow, CE AF Goldhaber-Fiebert, Sara N. Goldhaber-Fiebert, Jeremy D. Rosow, Carl E. TI Knowledge-based errors in anesthesia: a paired, controlled trial of learning and retention SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article ID HOSPITALIZED-PATIENTS; MORTALITY CONFERENCE; ADVERSE EVENTS; SIMULATOR; PERFORMANCE; PREVENTION; MANAGEMENT; MORBIDITY AB Purpose Optimizing patient safety by improving the training of physicians is a major challenge of medical education. In this pilot study, we hypothesized that a brief lecture, targeted to rare but potentially dangerous situations, could improve anesthesia practitioners' knowledge levels with significant retention of learning at six months. Methods In this paired controlled trial, anesthesia residents and attending physicians at Massachusetts General Hospital took the same 14-question multiple choice examination three times: at baseline, immediately after a brief lecture, and six months later. The lecture covered material on seven "intervention" questions; the remaining seven were "control" questions. The authors measured immediate knowledge acquisition, defined as the change in. percentage of correct answers on intervention questions between baseline and post-lecture, and measured learning retention as the difference between baseline and six months. Both measurements were corrected for change in performance on control questions. Results Fifty of the 89 subjects completed all three examinations. The post-lecture increase in percentage of questions answered correctly, adjusted for control, was 22.2% [95% confidence interval (CI) 16.0-28.4%; P < 0.01], while the adjusted increase at six months was 7.9% (95% Cl 1.1-14.7%; P = 0.024). Conclusion A brief lecture improved knowledge, and the subjects retained a significant amount of this learning at six months. Exposing residents or other practitioners to this type of inexpensive teaching intervention may help them to avoid preventable uncommon errors that are rooted in unfamiliarity with the situation or the equipment. The methods used for this study may also be applied to compare the effect of various other teaching modalities while, at the same time, preserving participant anonymity and making adjustments for ongoing learning. C1 [Goldhaber-Fiebert, Sara N.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford Hosp & Clin, Stanford, CA 94305 USA. [Goldhaber-Fiebert, Sara N.] VA Hlth Care Syst, Palo Alto, CA USA. [Goldhaber-Fiebert, Jeremy D.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Rosow, Carl E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Goldhaber-Fiebert, SN (reprint author), Stanford Univ, Sch Med, Dept Anesthesia, Stanford Hosp & Clin, 300 Pasteur Dr,Room H3580, Stanford, CA 94305 USA. EM sgf@post.harvard.edu NR 18 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD JAN PY 2009 VL 56 IS 1 BP 35 EP 45 DI 10.1007/s12630-008-9002-9 PG 11 WC Anesthesiology SC Anesthesiology GA 402KO UT WOS:000263012800006 PM 19247776 ER PT J AU Grinblatt, DL Yu, DH Hars, V Vardiman, JW Powell, BL Nattam, S Silverman, LR de Castro, C Stone, RM Bloomfield, CD Larson, RA AF Grinblatt, David L. Yu, Daohai Hars, Vera Vardiman, James W. Powell, Bayard L. Nattam, Sreenivasa Silverman, Lewis R. de Castro, Carlos, III Stone, Richard M. Bloomfield, Clara D. Larson, Richard A. CA Canc & Leukemia Grp B TI Treatment of Myelodysplastic Syndrome With 2 Schedules and Doses of Oral Topotecan A Randomized Phase 2 Trial by the Cancer and Leukemia Group B (CALGB 19803) SO CANCER LA English DT Article DE chronic myelomonocytic leukemia; cytogenetic risk group; French-American-British classification; International Prognostic Scoring System; pharmacokinetics; refractory cytopenia; topoisomerase I inhibitor; toxicity ID TOPOISOMERASE-I-INHIBITOR; COLONY-STIMULATING FACTOR; CHRONIC MYELOMONOCYTIC LEUKEMIA; QUALITY-OF-LIFE; CLASSIFICATION; LENALIDOMIDE; AZACITIDINE; THALIDOMIDE; DELETION; THERAPY AB BACKGROUND: The Cancer and Leukemia Group B evaluated oral topotecan administered at 2 schedules and doses for myelodysplastic syndrome (MDS). METHODS: Patients with previously untreated primary or therapy-related MDS were eligible. Patients with refractory anemia (RA), RA with ringed sideroblasts, or refractory cytopenia with multilineage dysplasia (RCMD) were eligible only if they were dependent on erythrocyte transfusion, had a platelet count <50,000/mu L, or had an absolute neutrophil count <1000/mu L with a recent infection that required antibiotics. Patients were randomized to receive oral topotecan either at a dose of 1.2 mg/m(2) twice daily for 5 days (Arm A) or once daily for 10 days (Arm B) repeated every 21 days for at least 2 cycles. Responding patients continued until they developed disease progression or unacceptable toxicity or until they had received 2 cycles beyond a complete response. RESULTS: Ninety patients received treatment, including 46 patients on Arm A and 44 patients on Arm B. Partial responses with improvement in all 3 cell lines occurred in 6 patients (7%), and hematologic improvement (in 1 or 2 cell lines) was observed in 21 patients (23%), for an overall response rate of 30%. Response duration was longer on Arm A (23 months vs 14 months; P=.02). Seven of 14 patients with chronic myelomonocytic leukemia responded. There were 8 treatment-related deaths from infection (6 deaths) and bleeding (2 deaths). Diarrhea was the most frequent nonhematologic toxicity (grade 3, 11%; grade 4, 2%; grading determined according to the National Cancer Institute Comman Toxicity Criteria v.2.0). CONCLUSIONS: Oral topotecan in the dose and schedules evaluated in this trial demonstrated only a modest response rate with a troublesome toxicity profile in the treatment of KIDS. Cancer 2009;115:84-93. (C) 2008 American Cancer Society. C1 [Grinblatt, David L.] Northshore Univ Hlth Syst, Div Hematol, Evanston, IL 60201 USA. [Yu, Daohai] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biostat, Tampa, FL 33682 USA. [Hars, Vera] Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. [Vardiman, James W.] Univ Chicago, Dept Pathol, Hematopathol Sect, Chicago, IL 60637 USA. [Powell, Bayard L.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Comprehens Canc, Winston Salem, NC USA. [Nattam, Sreenivasa] Ft Wayne Med Oncol Hematol, Ft Wayne, IN USA. [Silverman, Lewis R.] Mt Sinai Sch Med, Div Hematol Oncol, New York, NY USA. [de Castro, Carlos, III] Duke Univ, Ctr Comprehens Canc, Durham, NC USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Larson, Richard A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Larson, Richard A.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. RP Grinblatt, DL (reprint author), Northshore Univ Hlth Syst, Div Hematol, 2650 Ridge Ave,Room 5134, Evanston, IL 60201 USA. EM dgrinblatt@northshore.org OI Larson, Richard/0000-0001-9168-3203 FU Glaxo-Smith-Kline; National Cancer Institute [CA31946, CA33601]; [CA35199]; [CA41287]; [CA03927]; [CA04457]; [CA47577]; [CA32291]; [CA77658] FX Dr. Grinblatt is supported by CA35199. Dr. Hats is supported by CA33601. Dr. Vardiman is supported by CA41287. Dr. Powell is supported by CA03927. Dr. Nattam is supported by CA41287. Dr. Silverman is supported by CA04457. Dr. de Castro is supported by CA47577. Dr. Stone is supported by CA32291. Dr. Bloomfield is supported by CA77658. Dr. Larson is supported by CA41287. NR 27 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2009 VL 115 IS 1 BP 84 EP 93 DI 10.1002/cncr:23995 PG 10 WC Oncology SC Oncology GA 401MC UT WOS:000262943800012 PM 19025972 ER PT J AU Harisinghani, MG AF Harisinghani, Mukesh G. TI Nanoparticle Enhanced Imaging SO CANCER BIOMARKERS LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Director Abdominal MRI, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Director Abdominal MRI, Boston, MA 02114 USA. EM mharisinghani@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2009 VL 5 IS 2 BP 59 EP 59 DI 10.3233/CBM-2009-0614 PG 1 WC Oncology SC Oncology GA 442GM UT WOS:000265829400001 PM 19414921 ER PT J AU Islam, T Harisinghani, MG AF Islam, Tina Harisinghani, Mukesh G. TI Overview of nanoparticle use in cancer imaging SO CANCER BIOMARKERS LA English DT Article DE Ferumoxtran-10; ultrasmall superparamagnetic iron oxide particle (USPIO); lymph node; LNMRI; staging ID SUPERPARAMAGNETIC IRON-OXIDE; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASES; CELL LUNG-CANCER; INITIAL CLINICAL-EXPERIENCE; RECTAL-CANCER; MR LYMPHANGIOGRAPHY; PROSTATE-CANCER; PATHOLOGICAL CORRELATION; PELVIC MALIGNANCIES AB Current cross-sectional imaging modalities are inaccurate in characterizing nodal metastatic disease because of their use of size and/or morphology as differentiating factors. PET has overcome some of these limitations but it is constrained by its spacial resolution particularly for detecting small nodal metastases. These challenges have led to the development of lymphotropic contrast agents. Ferumoxtran-10 is one such MRI lymphotropic contrast agent that consists of ultrasmall superparamagnetic iron-oxide based nanoparticles targeted at the reticuloendothelial system. After intravenous administration ferumoxtran-10 is phagocytosed by macrophages which then accumulate within benign lymph nodes. Disturbances in lymph flow or in nodal architecture caused by metastases lead to abnormal patterns of accumulation of the particles, which are detectable by MRI. On postcontrast T2- and T2*-weighted MRI benign lymph nodes show a drop in signal intensity and homogenous darkening whereas areas of malignant infiltration show lack of nanoparticle uptake and remain signal-intense. Summary ROC curve analysis for per-lymph-node data showed an overall sensitivity of 88% and overall specificity of 96% for ferumoxtran-10-enhanced MRI. Ferumoxtran-10-enhanced MRI offers higher diagnostic precision than unenhanced MRI and is sensitive and specific for the detection of lymph-node metastases, especially in malignant diseases of the abdomen and pelvis. C1 [Islam, Tina; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Islam, Tina; Harisinghani, Mukesh G.] Ctr Mol Imaging Res, Charlestown, MA USA. RP Islam, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM islam.tina@mgh.harvard.edu NR 57 TC 46 Z9 49 U1 4 U2 17 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2009 VL 5 IS 2 BP 61 EP 67 DI 10.3233/CBM-2009-0578 PG 7 WC Oncology SC Oncology GA 442GM UT WOS:000265829400002 PM 19414922 ER PT J AU Islam, T Wolf, G AF Islam, Tina Wolf, Gerald TI The pharmacokinetics of the lymphotropic nanoparticle MRI contrast agent ferumoxtran-10 SO CANCER BIOMARKERS LA English DT Article DE Ferumoxtran-10; ultrasmall superparamagnetic iron oxide particle; MRI contrast agent; macrophage phagocytosis ID SUPERPARAMAGNETIC IRON-OXIDE; ANTIGEN-INDUCED ARTHRITIS; HEMATOPOIETIC PROGENITOR CELLS; CENTRAL-NERVOUS-SYSTEM; IN-VIVO TRACKING; MOUSE MODEL; ATHEROSCLEROTIC PLAQUE; HYPERLIPIDEMIC RABBITS; MYOCARDIAL-INFARCTION; LYMPH-NODES AB Ferumoxtran-10 is an ultrasmall superparamagnetic biodegradable iron oxide which serves as a MRI contrast agent in the differentiation of metastatic and non-metastatic lymph nodes in primary malignancies and imaging of phagocyte-associated disease processes. Ferumoxtran-10 is supplied as a lyophilized powder containing 210 mg of iron, 631 mg of dextran, and 27 mg of sodium citrate. The iron oxide core determines the magnetic properties of ferumoxtran-10, primarily its effects on the MR relaxation times, T1, T2, and T2*. Attachment of dextran prolongs the circulatory time of the nanoparticles. The intended human dose of ferumoxtran-10 is 2.6 mg Fe/kg. Reconstituted and diluted with physiological saline it is administered intravenously by means of a slow drip infusion. After initial vascular distribution of the particles, they are slowly phagocytosed by the reticuloendothelial system cells of the spleen, lymph nodes, bone marrow, and liver. When ferumoxtran-10 is present in phagocytic cells the iron oxide causes local magnetic field inhomogeneities which lead to increases in proton relaxation rates, resulting in signal loss on mid-T1/T2 or heavily T2-weighted MR images. Stored in lysosomes the particles are ultimately degraded: the iron enters the normal body iron metabolism cycle and dextran is eliminated mainly via the kidney. C1 [Islam, Tina] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Islam, Tina] Ctr Mol Imaging Res, Charlestown, MA USA. [Wolf, Gerald] AMAG Pharmaceut Inc, Cambridge, MA USA. RP Islam, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM islam.tina@mgh.harvard.edu NR 40 TC 12 Z9 13 U1 1 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2009 VL 5 IS 2 BP 69 EP 73 DI 10.3233/CBM-2009-0579 PG 5 WC Oncology SC Oncology GA 442GM UT WOS:000265829400003 PM 19414923 ER PT J AU Eisner, BH Feldman, AS AF Eisner, Brian H. Feldman, Adam S. TI Nanoparticle imaging for genitourinary cancers SO CANCER BIOMARKERS LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASES; PROSTATE-CANCER; CERVICAL-CARCINOMA; FROZEN SECTION; CT; MRI; FERUMOXTRAN-10; DISSECTION AB Lymphotrophic nanoparticle enhanced magnetic resonance imaging is a promising new diagnostic modality for lymph node staging in genitourinary malignancies. The technique utilizes ultrasmall superparamagnetic iron oxide particles to provide detailed characterization of lymph nodes for detection of metastatic disease. Early results have are promising for bladder, penile, prostate, and testicular cancer. This review provides an overview of the current state of lymphotrophic enhanced magnetic resonance imaging in genitourinary cancers. C1 [Eisner, Brian H.; Feldman, Adam S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 28 TC 5 Z9 5 U1 2 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2009 VL 5 IS 2 BP 75 EP 79 DI 10.3233/CBM-2009-0553 PG 5 WC Oncology SC Oncology GA 442GM UT WOS:000265829400004 PM 19414924 ER PT J AU Islam, T Josephson, L AF Islam, Tina Josephson, Lee TI Current state and future applications of active targeting in malignancies using superparamagnetic iron oxide nanoparticles SO CANCER BIOMARKERS LA English DT Article DE Superparamagnetic iron oxide nanoparticles (SPIO); magnetic resonance imaging; oncologic imaging; receptor imaging; targeted probe; multimodality imaging ID RECEPTOR-MEDIATED ENDOCYTOSIS; GENE-EXPRESSION ANALYSIS; HUMAN PROSTATE-CANCER; TRANSFERRIN RECEPTOR; FOLATE RECEPTOR; IN-VIVO; CONTRAST AGENT; DRUG-DELIVERY; TUMOR-CELLS; MULTIMODAL NANOPARTICLE AB Superparamagnetic iron oxide nanoparticles (SPIO) are novel MRI contrast agents. After cellular uptake, SPIO cause a negative T2 contrast in MRI. Passive targeting strategies rely on SPIO uptake in reticuloendothelial cells by receptor-mediated phagocytosis. Active targeting employs SPIO-conjugates with specific targeting ligands which selectively bind to biomarkers on target cells. Several receptor systems are overexpressed in cancerous diseases and have been investigated as targets for ligand-directed SPIO. Targeting receptors undergo repeated recycling to the cell surface and internalization and bind further SPIO, thereby amplifying the magnetic signal. Malignant cell degeneration may also lead to loss of specific receptor activity. SPIO-conjugates directed at those receptors lead to a prominent reduction in signal intensity in healthy tissue but not the tumor. These strategies allow for molecular profiling of target cells and potentially enable the early detection of malignant diseases, more accurate staging, and treatment monitoring. With the advent of multimodality imaging techniques like targeted nanoparticle-enhanced MRI and near infrared optical fluorescence imaging, the combined advantages of different systems can be exploited. C1 [Islam, Tina] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Islam, Tina; Josephson, Lee] Ctr Mol Imaging Res, Charlestown, MA USA. RP Islam, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM islam.tina@mgh.harvard.edu NR 80 TC 59 Z9 74 U1 1 U2 22 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2009 VL 5 IS 2 BP 99 EP 107 DI 10.3233/CBM-2009-0615 PG 9 WC Oncology SC Oncology GA 442GM UT WOS:000265829400007 PM 19414927 ER PT J AU Xiang, N Zhao, R Zhong, WX AF Xiang, Nong Zhao, Rui Zhong, Weixiong TI Sodium selenite induces apoptosis by generation of superoxide via the mitochondrial-dependent pathway in human prostate cancer cells SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Antioxidant enzymes; Apoptosis; Mitochondria; Selenium Superoxide ID OXIDATIVE STRESS; CARCINOSTATIC ACTIVITY; IONIZING-RADIATION; HEPG(2) CELLS; PREVENTION; SELENOMETHIONINE; RISK; CHEMOPREVENTION; METHIONINASE; INVOLVEMENT AB Purpose Studies have demonstrated that selenium supplementation reduces the incidence of cancer, particularly prostate cancer. Evidence from experimental studies suggests that apoptosis is a key event in cancer chemoprevention by selenium and reactive oxygen species play a role in induction of apoptosis by selenium compounds. The current study was designed to investigate the role of superoxide and mitochondria in selenite-induced apoptosis in human prostate cancer cells. Methods LNCaP cells were transduced with adenoviral constructs to overexpress four primary antioxidant enzymes: manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), or glutathione peroxidase 1 (GPx1). Cell viability, apoptosis, and superoxide production induced by sodium selenite were analyzed by the MTT assay, chemiluminescence, flow cytometry, western blot analysis, and Hoechst 33342 staining following overexpression of these antioxidant enzymes. Results Our study shows the following results: (1) selenite induced cancer cell death and apoptosis by producing superoxide radicals; ( 2) selenite-induced superoxide production, cell death, and apoptosis were inhibited by overexpression of MnSOD, but not by CuZnSOD, CAT, or GPx1; and (3) selenite treatment resulted in a decrease in mitochondrial membrane potential, release of cytochrome c into the cytosol, and activation of caspases 9 and 3, events that were suppressed by overexpression of MnSOD. Conclusions This study demonstrates that selenite induces cell death and apoptosis by production of superoxide in mitochondria and activation of the mitochondrial apoptotic pathway and MnSOD plays an important role in protection against prooxidant effects of superoxide from selenite. The data suggest that superoxide production in mitochondria is, at least in part, a key event in selenium-induced apoptosis in prostate cancer cells. C1 [Xiang, Nong; Zhao, Rui; Zhong, Weixiong] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Zhong, Weixiong] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. RP Zhong, WX (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI 53792 USA. EM wzhong3@wisc.edu FU National Cancer Institute [CA114281]; Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs FX We thank Dr. Jeanne Bourdeau-Heller for her technical assistance. This work was funded, in part, by grants from the National Cancer Institute (CA114281) and the Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs. NR 44 TC 54 Z9 59 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2009 VL 63 IS 2 BP 351 EP 362 DI 10.1007/s00280-008-0745-3 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 377XX UT WOS:000261286800018 PM 18379781 ER PT J AU Birmann, BM Tamimi, RM Giovannucci, E Rosner, B Hunter, DJ Kraft, P Mitsiades, C Anderson, KC Colditz, GA AF Birmann, Brenda M. Tamimi, Rulla M. Giovannucci, Edward Rosner, Bernard Hunter, David J. Kraft, Peter Mitsiades, Constantine Anderson, Kenneth C. Colditz, Graham A. TI Insulin-like Growth Factor-1-and Interleukin-6-related Gene Variation and Risk of Multiple Myeloma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NECROSIS-FACTOR-ALPHA; NATIONAL DEATH INDEX; BODY-MASS INDEX; FACTOR-I; PROSTATE-CANCER; MULTIETHNIC COHORT; BREAST-CANCER; RECEPTOR; ASSOCIATION; POLYMORPHISMS AB Insulin-like growth factor (IGF)-1 and interleukin (IL)-6 promote the proliferation and survival of multiple myeloma cells. Variation in genes related to IGF-1 and IL-6 signaling may influence susceptibility to multiple myeloma. To assess their etiologic role, we examined the association of 70 tagging single nucleotide polymorphisms (SNP) in seven IGF-1 and three IL-6 pathway genes with multiple myeloma risk in two prospective cohorts, the Nurses' Health Study and the Health Professionals Follow-up Study. Among the participants who provided DNA specimens, we identified 58 women and 24 men with multiple myeloma and matched two controls per case. We used multivariable logistic regression models to assess the association of the SNPs or tagged haplotypes with multiple myeloma risk. Several SNPs had suggestive associations with multiple myeloma based on large odds ratios (OR), although the corresponding omnibus P values were not more than nominally significant (i.e., at P < 0.05). These SNPs included rs1801278 in the gene encoding insulin receptor substrate-1 [IRS1; C/T versus C/C genotypes; OR, 4.3; 95% confidence interval (CI), 1.5-12.1] and three IL-6 receptor SNPs: rs6684439 (T/T versus C/C; OR, 2.9; 95% CI, 1.2-7.0), rs7529229 (C/C versus T/T; OR, 2.5; 95% CI, 1.1-6.0), and rs8192284 (C/C versus A/A; OR, 2.5, 95% CI, 1.16.0). Additional SNPs in genes encoding IGF-1, IGF binding protein-2, IRS2, and gp130 also showed suggestive associations with multiple myeloma risk. We conducted a large number of statistical tests, and the findings may be due to chance. Nonetheless, the data are consistent with the hypothesis that IGF-1 and IL-6-related gene variation influences susceptibility to multiple myeloma and warrant confirmation in larger populations. (Cancer Epidemiol Biomarkers Prev 2009;18(1):282-8) C1 [Birmann, Brenda M.; Tamimi, Rulla M.; Giovannucci, Edward; Rosner, Bernard; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Tamimi, Rulla M.; Giovannucci, Edward; Kraft, Peter; Colditz, Graham A.] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. [Giovannucci, Edward] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA. [Rosner, Bernard; Kraft, Peter] Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Mitsiades, Constantine; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. [Colditz, Graham A.] Barnes Jewish Hosp, St Louis, MO 63110 USA. RP Birmann, BM (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM brenda.birmann@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [K07 CA115687-01A1, CA10070, CA55075, CA87969, K07 CA115687, K07 CA115687-02, K07 CA115687-03, P01 CA055075, P01 CA087969, R01 CA127435, R01 CA127435-01] NR 49 TC 24 Z9 26 U1 0 U2 1 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 JAN PY 2009 VL 18 IS 1 BP 282 EP 288 DI 10.1158/1055-9965.EPI-08-0778 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200037 PM 19124510 ER PT J AU Irwin, ML Varma, K Alvarez-Reeves, M Cadmus, L Wiley, A Chung, GG DiPietro, L Mayne, ST Yu, H AF Irwin, Melinda L. Varma, Katie Alvarez-Reeves, Marty Cadmus, Lisa Wiley, Andrew Chung, Gina G. DiPietro, Loretta Mayne, Susan T. Yu, Herbert TI Randomized Controlled Trial of Aerobic Exercise on Insulin and Insulin-like Growth Factors in Breast Cancer Survivors: The Yale Exercise and Survivorship Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IGF-BINDING PROTEIN-3; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; FACTOR-I; BODY-COMPOSITION; FASTING INSULIN; CLINICAL-TRIAL; LIFE-STYLE; C-PEPTIDE; RISK AB Background: High insulin and insulin-like growth factor-I (IGF-I) levels may be associated with an increased breast cancer risk and/or death. Given the need to identify modifiable factors that decrease insulin, IGF-I, and breast cancer risk and death, we investigated the effects of a 6-month randomized controlled aerobic exercise intervention versus usual care on fasting insulin, IGF-I, and its binding protein (IGFBP-3) in postmenopausal breast cancer survivors. Methods: Seventy-five postmenopausal breast cancer survivors were identified from the Yale-New Haven Hospital Tumor Registry and randomly assigned to an exercise (n = 37) or usual care (n = 38) group. The exercise group participated in 150 minutes per week of moderate-intensity aerobic exercise. The usual care group was instructed to maintain their current physical activity level. A fasting blood sample was collected on each study participant at baseline and 6 months. Blood levels of insulin and IGF were measured with ELISA. Results: On average, exercisers increased aerobic exercise by 129 minutes per week compared with 45 minutes per week among usual care participants (P < 0.001). Women randomized to exercise experienced decreases in insulin, IGF-I, and IGFBP-3, whereas women randomized to usual care had increases in these hormones. Between-group differences in insulin, IGF-I, and IGFBP-3 were 20.7% (P = 0.089), 8.9% (P = 0.026), and 7.9% (P = 0.006), respectively. Conclusions: Moderate-intensity aerobic exercise, such as brisk walking, decreases IGF-I and IGFBP-3. The exercise-induced decreases in IGF may mediate the observed association between higher levels of physical activity and improved survival in women diagnosed with breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(1):306-1.3) C1 [Irwin, Melinda L.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [DiPietro, Loretta] John B Pierce Fdn Lab, New Haven, CT 06519 USA. [Alvarez-Reeves, Marty] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Irwin, ML (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu FU American Cancer Society [MRSC-04-006-01-CPH]; Susan G. Komen Breast Cancer Foundation [BCTR0201916]; National Center of Research Resources; NIH [M01-RR00125] FX American Cancer Society (MRSC-04-006-01-CPH) and the Susan G. Komen Breast Cancer Foundation (BCTR0201916). Supported in part by a General Clinical Research Center grant from the National Center of Research Resources, NIH (grant M01-RR00125), awarded to Yale University School of Medicine. NR 36 TC 108 Z9 111 U1 1 U2 9 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 JAN PY 2009 VL 18 IS 1 BP 306 EP 313 DI 10.1158/1055-9965.EPI-08-0531 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200040 PM 19124513 ER PT J AU Anderson, KS AF Anderson, Karen S. TI Tumor Vaccines for Breast Cancer SO CANCER INVESTIGATION LA English DT Review ID REGULATORY T-CELLS; PHASE-I TRIAL; ANTIGEN-4 MONOCLONAL-ANTIBODY; TRANSFECTED DENDRITIC CELLS; COLONY-STIMULATING FACTOR; HIGH-DOSE CHEMOTHERAPY; METASTATIC BREAST; IMMUNE-RESPONSE; OVARIAN-CANCER; CLINICAL-RESPONSES C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, 44 Binney St, Boston, MA 02115 USA. FU NIH, NCI [3P30 CA006516-41S4, U01 CA117374]; AVON Foundation FX This work is supported by grants from the NIH, NCI (3P30 CA006516-41S4 and U01 CA117374), and the AVON Foundation. The author thanks Dr. Ellis Reinherz and Dr. Glenn Dranoff for critical review, and Victoria Alexander for editorial assistance. NR 115 TC 19 Z9 22 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 EI 1532-4192 J9 CANCER INVEST JI Cancer Invest. PY 2009 VL 27 IS 4 BP 361 EP 368 AR PII 910345459 DI 10.1080/07357900802574421 PG 8 WC Oncology SC Oncology GA 434RI UT WOS:000265291400001 PM 19358018 ER PT J AU Ku, GY O'Reilly, EM Saltz, LB Schrag, D Maki, RG Kelsen, DP Ilson, DH AF Ku, Geoffrey Y. O'Reilly, Eileen M. Saltz, Leonard B. Schrag, Deborah Maki, Robert G. Kelsen, David P. Ilson, David H. TI Phase I Study of Weekly Cisplatin, Bolus Fluorouracil and Escalating Doses of Irinotecan in Advanced Solid Tumors SO CANCER INVESTIGATION LA English DT Article DE Cisplatin; 5-Fluorouracil; Irinotecan; Phase I trial ID METASTATIC COLORECTAL-CANCER; ADVANCED ESOPHAGEAL CANCER; RANDOMIZED-TRIAL; PLUS FLUOROURACIL; ORAL CAPECITABINE; GASTRIC-CANCER; RADIOTHERAPY; LEUCOVORIN; CHEMOTHERAPY; EPIRUBICIN AB Purpose: We performed a phase I study of 5-fluorouracil (5-FU), cisplatin and irinotecan. Methods: Twenty-nine patients received cisplatin 25 mg/m2 and bolus 5-FU 425 mg/m2, along with irinotecan at 40, 50, and 65 mg/m2 weekly for 4 out of 6 weeks. Results: The maximum tolerated dose (MTD) for untreated patients was irinotecan 65 mg/m2 while the MTD for previously treated patients was irinotecan 40 mg/m2. Neutropenia and diarrhea were the major dose-limiting toxicities. Antitumor activity was noted in gastric, esophageal and pancreatic cancers. Conclusion: Because of the toxicity profile, combinations with continuous infusion 5-FU or capecitabine should be explored. C1 [Ku, Geoffrey Y.; O'Reilly, Eileen M.; Saltz, Leonard B.; Kelsen, David P.; Ilson, David H.] Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, Dept Med, New York, NY 10065 USA. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma & Sarcoma Serv, New York, NY 10021 USA. [Schrag, Deborah] Dana Farber Canc Inst, Ctr Gastrointestinal Oncol, Boston, MA 02115 USA. RP Ilson, DH (reprint author), Mem Sloan Kettering Canc Ctr, Gastrointestinal Oncol Serv, Dept Med, 1275 York Ave, New York, NY 10065 USA. EM ilsond@mskcc.org OI Ku, Geoffrey/0000-0002-0448-1038; Saltz, Leonard/0000-0001-8353-4670 NR 19 TC 0 Z9 0 U1 0 U2 1 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. PY 2009 VL 27 IS 4 BP 402 EP 406 AR PII 908714826 DI 10.1080/07357900802406327 PG 5 WC Oncology SC Oncology GA 434RI UT WOS:000265291400007 PM 19219674 ER PT J AU Bober, SL AF Bober, Sharon L. TI From the Guest Editor Out in the Open: Addressing Sexual Health After Cancer SO CANCER JOURNAL LA English DT Editorial Material C1 [Bober, Sharon L.] Dana Farber Canc Inst, Lance Armstrong Fdn, Adult Survivorship Clin, Boston, MA 02115 USA. RP Bober, SL (reprint author), Dana Farber Canc Inst, Lance Armstrong Adult Survivorship Clin, Sexual Hlth Program, 44 Binney St,Dana 321, Boston, MA 02115 USA. EM sharon_bober@dfci.harvard.edu NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2009 VL 15 IS 1 BP 13 EP 14 PG 2 WC Oncology SC Oncology GA 405FA UT WOS:000263207000003 PM 19197167 ER PT J AU Matloff, ET Barnett, RE Bober, SL AF Matloff, Ellen T. Barnett, Rachel E. Bober, Sharon L. TI Unraveling the Next Chapter Sexual Development, Body Image, and Sexual Functioning in Female BRCA Carriers SO CANCER JOURNAL LA English DT Article DE BRCA1; BRCA2; sexuality; fertility; body image ID CONTRALATERAL BREAST-CANCER; REDUCING SALPINGO-OOPHORECTOMY; QUALITY-OF-LIFE; OVARIAN-CANCER; MUTATION CARRIERS; HEREDITARY BREAST; FAMILY-HISTORY; RISK; SUSCEPTIBILITY; WOMEN AB Clinical genetic testing for BRCA1 and BRCA2 has become available in the past 15 years, and it has been established that female BRCA carriers have a high lifetime risk to develop both breast and ovarian cancer. Predisposition testing makes it possible to predict risk in families and to tailor medical management accordingly. In addition to close surveillance, prophylactic mastectomy and oophorectomy are primary risk reduction strategies offered to BRCA carriers. Although the emphasis of research thus far has been on the efficacy of surveillance and risk reduction strategies, it has become clear that genetic testing and the resulting medical decisions around risk reduction lead to a unique set of emotional, physical, and sexual issues for female BRCA carriers and their children. This article will focus oil those issues in unaffected female BRCA carriers. C1 [Matloff, Ellen T.; Barnett, Rachel E.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06510 USA. [Matloff, Ellen T.] Yale Univ, Sch Med, Dept Genet, New Haven, CT USA. [Bober, Sharon L.] Dana Farber Canc Inst, Lance Armstrong Fdn, Adult Survivorship Clin, Boston, MA 02115 USA. RP Matloff, ET (reprint author), Yale Univ, Sch Med, Yale Canc Ctr, 55 Church St,Suite 402, New Haven, CT 06510 USA. EM ellen.matloff@yale.edu NR 34 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2009 VL 15 IS 1 BP 15 EP 18 PG 4 WC Oncology SC Oncology GA 405FA UT WOS:000263207000004 PM 19197168 ER PT J AU Latini, DM Hart, SL Coon, DW Knight, SJ AF Latini, David M. Hart, Stacely L. Coon, David W. Knight, Sara J. TI Sexual Rehabilitation After Localized Prostate Cancer Current Interventions and Future Directions SO CANCER JOURNAL LA English DT Article DE prostate cancer; symptom management; psychosocial interventions; conceptual model ID QUALITY-OF-LIFE; SELF-MANAGEMENT PROGRAM; LOW-INCOME PATIENTS; RADICAL PROSTATECTOMY; ERECTILE DYSFUNCTION; STRESS-MANAGEMENT; RANDOMIZED-TRIAL; SUPPORT GROUPS; HEALTH-STATUS; STEPPED CARE AB Many published articles have documented the impact of prostate-cancer treatment on sexual functioning in men treated for localized disease. Surprisingly, the literature on interventions to rehabilitate men's sexual functioning is much more limited. In this article, we review the sexual-rehabilitation interventions for prostate-cancer patients and identify a number of common themes across interventions. We also identify areas where further research is needed and propose a conceptual model based on psychologic and nursing theories and informed by the published research. C1 [Latini, David M.] Michael E DeBakey VA Med Ctr, Dev Ctr Excellence, Houston, TX USA. [Latini, David M.] Michael E DeBakey VA Med Ctr, Hlth Serv Res, Houston, TX USA. [Latini, David M.] Michael E DeBakey VA Med Ctr, Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX USA. [Latini, David M.] Michael E DeBakey VA Med Ctr, Scott Dept Urol, Houston, TX USA. [Hart, Stacely L.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Coon, David W.] Arizona State Univ, Coll Nursing & Healthcare Innovat, Phoenix, AZ USA. [Knight, Sara J.] Univ Calif San Francisco, San Francisco Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Knight, Sara J.] Genitourinary Canc Epidemiol & Populat Sci Progra, Dept Psychiat, San Francisco, CA USA. [Knight, Sara J.] Genitourinary Canc Epidemiol & Populat Sci Progra, Dept Urol, San Francisco, CA USA. [Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Latini, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, HSR&D Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM david.latini@va.gov RI Hart, Stacey/E-4819-2011; OI Latini, David/0000-0002-6161-4861 FU National Cancer Institute [R03 CA101586, R03 CA128475]; Health Services Research & Development Center of Excellence; Michael E. DeBakey Veterans Affairs Medical Center [HFP90-020]; American Cancer Society [06-083-01-CPPB] FX Supported by National Cancer Institute grants R03 CA101586 (to D.M.L.) and R03 CA128475 (to D.W.C.), in part by Health Services Research & Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center grant HFP90-020, and the American Cancer Society Grant 06-083-01-CPPB (to D.M.L.). NR 60 TC 15 Z9 16 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2009 VL 15 IS 1 BP 34 EP 40 PG 7 WC Oncology SC Oncology GA 405FA UT WOS:000263207000007 PM 19197171 ER PT J AU Knight, SJ Latini, DM AF Knight, Sara J. Latini, David M. TI Sexual Side Effects and Prostate Cancer Treatment Decisions Patient Information Needs and Preferences SO CANCER JOURNAL LA English DT Article DE prostate; cancer treatment; sexual side effects ID QUALITY-OF-LIFE; TREATMENT CHOICES; HEALTH STATES; UTILITIES; MEN; AIDS; PREDICTORS; MANAGEMENT; CARCINOMA; OUTCOMES AB Prostate cancer treatment decision making requires complex trade-offs among treatment outcomes, and sexual function is a central consideration for most men. Although sexual function is included in prostate cancer decision models, survival and fear of recurrence and cancer progression weigh more heavily in these decisions for many men than concerns about treatment impact on sexuality. In this article, we discuss the importance of sexuality in men's treatment decisions for prostate cancer. We focus on men's preferences for maintaining sexual function and their needs for information about the risk of sexual side effects with prostate cancer treatment. Our review suggests that among men diagnosed with prostate cancer sexual function is less important to men than concerns about survival, but is more highly valued than other side effects and treatment characteristics. However, there is evidence that concerns about sexuality are not in proportion with the associated risk for sexual problems with prostate cancer treatment and men acknowledge unmet needs for information about sexuality in making prostate cancer treatment decisions. C1 [Knight, Sara J.] Univ Calif San Francisco, San Francisco VA Med Ctr, Program Improve Care Vet Complex Comorbid Condit, San Francisco, CA 94121 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94121 USA. [Latini, David M.] Baylor Coll Med, Michael E DcBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Scott Dept Urol, Houston, TX 77030 USA. [Latini, David M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. RP Knight, SJ (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Program Improve Care Vet Complex Comorbid Condit, 4150 Clement St, San Francisco, CA 94121 USA. EM sara.knight@med.va.gov OI Latini, David/0000-0002-6161-4861 FU Veterans Administration (VA) Health Services Research and Development [IIR02-142-1]; Health Services Research & Development Center of Excellence [HFP90-020]; Mentored Research Scholar [06-083-01-CPPB]; American Cancer Society FX The contents of this work are solely the responsibility of the author and do not necessarily represent the official views of the Department of Veterans Affairs. NR 45 TC 14 Z9 15 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2009 VL 15 IS 1 BP 41 EP 44 PG 4 WC Oncology SC Oncology GA 405FA UT WOS:000263207000008 PM 19197172 ER PT J AU Park, ER Norris, RL Bober, SL AF Park, Elyse R. Norris, Rebecca L. Bober, Sharon L. TI Sexual Health Communication During Cancer Care Barriers and Recommendations SO CANCER JOURNAL LA English DT Article DE sexuality; communication; communication barriers; cancer ID BREAST-CANCER; OVARIAN-CANCER; PATIENT; INTIMACY; ISSUES; DYSFUNCTION; INFORMATION; ADJUSTMENT; SURVIVORS; NEEDS AB With improved cancer survival rates, it is becoming increasingly important to focus on quality of life issues throughout all stages of cancer treatment. Sexual problems often result from the physical and psychological side effects associated with cancer and cancer treatment regimens, yet few cancer patients recall discussing sexual risks before treatment or treatment options for sexual dysfunction after treatment. This review summarizes the literature, to date, on patient and clinician communication about sexual dysfunction. Patients' views about the importance of these discussions and patient and clinician barriers to sexual dysfunction communication are presented. We adapted a behavioral health counseling model, the 5 A's, and present it as a proposed framework for sexual health communication with cancer patients in a multidisciplinary setting. C1 [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. [Norris, Rebecca L.] Univ Massachusetts, Dept Psychiat, Boston, MA 02125 USA. [Bober, Sharon L.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Sexual Hlth Program,Perini Family Survivors Ctr, Boston, MA 02114 USA. RP Park, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org FU American Cancer Society's Mentored Research Scholar Award [MRSG-005-05-CPPB] FX Supported by a grant from the American Cancer Society's Mentored Research Scholar Award (MRSG-005-05-CPPB). NR 31 TC 56 Z9 56 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2009 VL 15 IS 1 BP 74 EP 77 PG 4 WC Oncology SC Oncology GA 405FA UT WOS:000263207000014 PM 19197178 ER PT J AU Menon, R Zhang, Q Zhang, Y Fermin, D Bardeesy, N DePinho, RA Lu, C Hanash, SM Omenn, GS States, DJ AF Menon, Rajasree Zhang, Qing Zhang, Yan Fermin, Damian Bardeesy, Nabeel DePinho, Ronald A. Lu, Chunxia Hanash, Samir M. Omenn, Gilbert S. States, David J. TI Identification of Novel Alternative Splice Isoforms of Circulating Proteins in a Mouse Model of Human Pancreatic Cancer SO CANCER RESEARCH LA English DT Article ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE GENE; TUMOR M2-PYRUVATE KINASE; MESSENGER-RNA; DUCTAL ADENOCARCINOMA; QUANTITATIVE-ANALYSIS; OXIDATIVE-METABOLISM; GLUCOSE-METABOLISM; MASS-SPECTROMETRY; PYRUVATE-KINASE; PROSTATE-CANCER AB To assess the potential of tumor-associated, alternatively spliced gene products as a source of biomarkers in biological fluids, we have analyzed a large data set of mass spectra derived from the plasma proteome of a mouse model of human pancreatic ductal adenocarcinoma. MS/MS spectra were interrogated for novel splice isoforms using a non-redundant database containing an exhaustive three-frame translation of Ensembl transcripts and gene models from ECgene. This integrated analysis identified 420 distinct splice isoforms, of which 92 did not match any previously annotated mouse protein sequence. We chose seven of those novel variants for validation by reverse transcription-PCR. The results were concordant with the proteomic analysis. All seven novel peptides were successfully amplified in pancreas specimens from both wild-type and mutant mice. Isotopic labeling of cysteine-containing peptides from tumor-bearing mice and wild-type controls enabled relative quantification of the proteins. Differential expression between tumor-bearing and control mice was notable for peptides from novel variants of muscle pyruvate kinase, malate dehydrogenase 1, glyceraldehyde-3-phosphate dehydrogenase, proteoglycan 4, minichromosome maintenance, complex component 9, high mobility group box 2, and hepatocyte growth factor activator. Our results show that, in a mouse model for human pancreatic cancer, novel and differentially expressed alternative splice isoforms are detectable in plasma and may be a source of candidate biomarkers. [Cancer Res 2009;69(1):300-9] C1 [Menon, Rajasree; Zhang, Yan; Fermin, Damian; Omenn, Gilbert S.; States, David J.] Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA. [Zhang, Qing; Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [DePinho, Ronald A.] Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Boston, MA USA. RP States, DJ (reprint author), Univ Michigan, Ctr Computat Med & Biol, 100 Washtenaw Ave, Ann Arbor, MI 48109 USA. EM dstates@umnich.edu OI Omenn, Gilbert S./0000-0002-8976-6074 FU National Cancer Institute (NCI)/SAIC [23XS110A]; MTTC [R01 LM008106]; MMHCC [U01 CA84313]; NCI PDAC [P01 IPOICA117969-01]; National Center for Integrative Biomedical Informatics [U54 DA021519]; National Resource for Pathways and Proteomics [P41 RR018627]; NCI Early Detection Research Network FX Grant support: National Cancer Institute (NCI)/SAIC contract 23XS110A on Mouse Models of Human Cancers, MTTC GR 687 for Proteomics Alliance for Cancer Research, R01 LM008106 Automated Genome Annotation. MMHCC U01 CA84313, NCI PDAC P01 IPOICA117969-01, U54 DA021519 National Center for Integrative Biomedical Informatics, P41 RR018627 National Resource for Pathways and Proteomics, and NCI Early Detection Research Network. NR 50 TC 56 Z9 57 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2009 VL 69 IS 1 BP 300 EP 309 DI 10.1158/0008-5472.CAN-08-2145 PG 10 WC Oncology SC Oncology GA 391ZQ UT WOS:000262273100038 PM 19118015 ER PT S AU Dovey, MC Zon, LI AF Dovey, Michael C. Zon, Leonard I. BE Yu, JS TI Defining Cancer Stem Cells by Xenotransplantation in Zebrafish SO CANCER STEM CELLS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Zebrafish; Cancer stem cells; Transplantation; Metastasis ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELL; TRANSPLANTATION; IDENTIFICATION; TUMORS AB The zebrafish (Danio rerio) has become an increasingly utilized and relevant model organism in the study of cancer. The use of transgenic and reverse genetic approaches has yielded several strains that model a variety of human neoplasms. In addition to modeling human disease, these strains provide a platform for the analysis of tumor stem cells. Here we describe the basic technique for the isolation and transplantation of tumor tissue in the zebrafish. This technique was designed to study metastasis and invasive potential of zebrafish tumor cells. Additionally, the basic protocol can be modified in order to describe cancer stem cell characteristics, including proliferative capacity, self-renewal, and the minimum number of tumor cells required for engraftment. C1 [Dovey, Michael C.; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Div Hematol, Oncol Childrens Hosp, Boston, MA USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Dovey, MC (reprint author), Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. NR 13 TC 11 Z9 12 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-938-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 568 BP 1 EP 5 DI 10.1007/978-1-59745-280-9_1 D2 10.1007/978-1-59745-280-9 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BLU09 UT WOS:000271014800001 PM 19582417 ER PT S AU Dranoff, G AF Dranoff, Glenn BE Steinman, R Banchereau, J Finn, OJ TI Targets of Protective Tumor Immunity SO CANCER VACCINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th International Cancer Vaccine Symposium CY OCT 28-30, 2008 CL New York, NY SP New York Acad Sci DE GM-CSF; CTLA-4; MICA; ERp5; NKG2D; myeloma ID COLONY-STIMULATING FACTOR; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; T-CELL RESPONSES; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; COMBINATION IMMUNOTHERAPY; ANTIBODY BLOCKADE; MULTIPLE-MYELOMA; CANCER; CTLA-4 AB The identification of antigens associated with tumor destruction is a major goal of cancer immunology. Several genetic and biochemical techniques have revealed a broad range of gene products that elicit immune recognition in cancer patients, but the biologic importance of these responses in most cases is poorly understood. While some targets are linked to tumor regressions in the context of adoptive cellular therapies or cancer vaccinations, the possible roles of immunity to most antigens in disease pathogenesis and clinical outcomes remain to be elucidated. One strategy for characterizing antigens that elicit clinically significant immune recognition involves the study of patients who achieve durable clinical benefits from immune treatments. Through this approach, we uncovered the immunogenicity of major histocompatibility chain-related protein A (MICA), which is a ligand for NKG2D, and ERp5, a protein disulfide isomerase involved in MICA shedding. Our findings suggest that components of the NKG2D pathway may be attractive targets for therapeutic monoclonal antibodies. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu NR 44 TC 20 Z9 21 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-759-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1174 BP 74 EP 80 DI 10.1111/j.1749-6632.2009.04938.x PG 7 WC Oncology; Multidisciplinary Sciences SC Oncology; Science & Technology - Other Topics GA BMC20 UT WOS:000271828500010 PM 19769739 ER PT J AU Wei, C AF Wei, C. TI Toll-like Receptors and Cardiac Injury SO CARDIOLOGY LA English DT Meeting Abstract C1 [Wei, C.] Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2009 VL 114 BP 85 EP 85 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 527QR UT WOS:000272382100160 ER PT J AU Guterbaum, T Braunstein, T Raunso, J Akram, S Hermann, T Rask-Madsen, C Ihlemann, N Torp-Pedersen, C Kober, L Dominguez, H AF Guterbaum, Thomas Braunstein, Thomas Raunso, Jakob Akram, Sumarra Hermann, Thomas Rask-Madsen, Christian Ihlemann, Nikolaj Torp-Pedersen, Christian Kober, Lars Dominguez, Helena TI Glucose is not the main determinant but contributes to endothelial dysfunction in a reperfusion model in vitro SO CARDIOLOGY LA English DT Meeting Abstract C1 [Guterbaum, Thomas; Braunstein, Thomas] Univ Copenhagen, Dept Biomed Sci, Copenhagen, Denmark. [Raunso, Jakob; Akram, Sumarra; Torp-Pedersen, Christian; Dominguez, Helena] Gentofte Univ Hosp, Hellerup, Denmark. [Hermann, Thomas; Ihlemann, Nikolaj; Kober, Lars] Rigshosp, Ctr Heart, DK-2100 Copenhagen, Denmark. [Rask-Madsen, Christian] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. RI Braunstein, Thomas Hartig/B-8064-2008; Torp-Pedersen, Christian/E-5931-2013; OI Braunstein, Thomas Hartig/0000-0001-6632-7960; DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2009 VL 113 BP 73 EP 73 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 452WV UT WOS:000266572800075 ER PT J AU Prunier, F Pottier, P Clairand, R Mercier, A Hajjar, RJ Planchon, B Furber, A AF Prunier, F. Pottier, P. Clairand, R. Mercier, A. Hajjar, R. J. Planchon, B. Furber, A. TI Chronic Erythropoietin Treatment Decreases Post-Infarct Myocardial Damage in Rats without Venous Thrombogenic Effect SO CARDIOLOGY LA English DT Article DE Erythropoietin; Cardioprotection; Myocardial infarction; Thrombosis ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; ISCHEMIA-REPERFUSION INJURY; HEART; PROTECTS; THERAPY; CARDIOPROTECTION; FIBRINOLYSIS; THROMBOSIS; PATHWAYS; HYPOXIA AB Objectives: Whereas administration of erythropoietin (EPO) acutely after myocardial infarction (MI) reduces infarct size and chronic EPO therapy attenuates post-MI remodeling, the safety of chronic EPO therapy following MI is unknown. Therefore, we examined the thrombogenic effects of a chronic EPO therapy after MI. Methods: Rats underwent coronary occlusion followed by reperfusion. They were assigned to one of the following groups: EPO-A, single injection of EPO 5,000 U/kg at the time of reperfusion; EPO- C, injection of EPO 5,000 U/kg at the time of reperfusion followed by 300 U/ kg/week; PBS-C, injection of vehicle only. After eight weeks of treatment they were exposed to a validated prethrombotic test based on partial stenosis of the inferior vena cava. Results: As compared to the rats receiving vehicle only, the rats treated with EPO exhibited a significant reduction in MI size ( 28.7 +/- 2.1% and 25.8 +/- 1.9 vs. 39.8 +/- 3.0% in EPO-A, EPO-C and PBS-C, respectively; p < 0.05). Whereas the hematocrit was significantly increased in EPO-C (59.7 +/- 2.0% vs. 44.7 +/- 0.9% in EPO-A, p < 0.001), the proportion of rats in which a thrombus occurred was similar in all groups (p = 0.52). Conclusion: Chronic EPO therapy added to the single high dose of EPO injected acutely did not induce venous pro-thrombotic effect in rats. Copyright (C) 2008 S. Karger AG, Basel C1 [Prunier, F.; Pottier, P.; Clairand, R.; Mercier, A.; Furber, A.] Fac Med, UPRES EA 3860, FR-49054 Angers 1, France. [Prunier, F.; Pottier, P.; Clairand, R.; Mercier, A.; Furber, A.] CHU Angers, Angers, France. [Pottier, P.; Planchon, B.] CHU Nantes, Serv Med Interne, F-44035 Nantes, France. [Hajjar, R. J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Prunier, F (reprint author), Fac Med, UPRES EA 3860, Rue Haute Reculee, FR-49054 Angers 1, France. EM faprunier@chu-angers.fr FU from Academie Nationale de Medecine, France FX We would like to thank Mr. Pierre Legras and Mr. Jerome Leroux from the animal facility for providing us technical assistance with the animals. Dr. A. Mercier was supported by a grant from Academie Nationale de Medecine, France. NR 23 TC 3 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2009 VL 112 IS 2 BP 129 EP 134 DI 10.1159/000142723 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 372HI UT WOS:000260892300007 PM 18596374 ER PT J AU Siddiqi, NH Khan, AJ Devlin, PM AF Siddiqi, Nasir H. Khan, Atif J. Devlin, Phillip M. TI Palonosetron-A Single-Dose Antiemetic Adjunct for Hepatic Artery Radioembolization: A Feasibility Study SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Yttrium-90 spheres; Palonosetron; Postembolization syndrome (PES); Radioembolization (RE); Selective internal radiation therapy (SIRT) ID CHEMOTHERAPY-INDUCED NAUSEA; MODERATELY EMETOGENIC CHEMOTHERAPY; PHASE-III; LIVER METASTASES; DOUBLE-BLIND; ONDANSETRON; TRIAL; BRACHYTHERAPY; ANTAGONISTS; PREVENTION AB Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after the procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits. C1 [Siddiqi, Nasir H.] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Khan, Atif J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ 08901 USA. [Devlin, Phillip M.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Siddiqi, NH (reprint author), Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, 510 S Kingshighway, St Louis, MO 63110 USA. EM siddiqin@mir.wustl.edu OI Khan, Atif/0000-0001-8640-8530 NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JAN PY 2009 VL 32 IS 1 BP 47 EP 51 DI 10.1007/s00270-008-9428-z PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 404CK UT WOS:000263128100007 PM 18779994 ER PT B AU Frankel, DS Meigs, JB AF Frankel, David S. Meigs, James B. BE Fonseca, VA TI Epidemiology and Prevention of Cardiovascular Disease in Diabetes SO CARDIOVASCULAR ENDOCRINOLOGY-BOOK: SHARED PATHWAYS AND CLINICAL CROSSROADS SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Diabetes; Cardiovascular disease; Epidemiology; Prevention; Risk factor modification; Blood pressure; Lipids; Glycemic control ID RANDOMIZED CONTROLLED-TRIAL; CONGESTIVE-HEART-FAILURE; CONVERTING-ENZYME-INHIBITOR; PRIOR MYOCARDIAL-INFARCTION; PLACEBO-CONTROLLED TRIAL; CORONARY-ARTERY DISEASE; CIGARETTE-SMOKING; BLOOD-PRESSURE; MICROVASCULAR COMPLICATIONS; VENTRICULAR DYSFUNCTION AB Diabetes is a common disease with a rapidly increasing prevalence. Diabetic patients are at markedly increased risk for development of coronary artery disease (CAD) and heart failure and, further, when they develop these diseases, they have worse outcomes including higher mortality. This mandates an aggressive approach to reducing cardiovascular risk in all diabetic patients. Good evidence has shown that tight blood pressure (BP), lipid and glycemic control, as well as smoking cessation, all substantially decrease the risk of cardiovascular disease and death. C1 [Frankel, David S.; Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Clin Epidemiol Unit,Dept Med, Boston, MA 02115 USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Res Unit, Boston, MA USA. RP Frankel, DS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Clin Epidemiol Unit,Dept Med, Boston, MA 02115 USA. NR 67 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-850-8 J9 CONTEMP ENDOCRINOL S PY 2009 BP 19 EP + DI 10.1007/978-1-59745-141-3_2 D2 10.1007/978-1-59745-141-3 PG 16 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA BJR31 UT WOS:000267022400002 ER PT S AU Smith, JG Newton-Cheh, C AF Smith, J. Gustav Newton-Cheh, Christopher BE DiPetrillo, K TI Genome-Wide Association Study in Humans SO CARDIOVASCULAR GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Genome-wide association study; GWAS; whole-genome association study; WGAS; complex genetics; common variation ID HARDY-WEINBERG EQUILIBRIUM; COMPLEX HUMAN-DISEASES; GENETIC ASSOCIATION; COMMON VARIANTS; HAPLOTYPE MAP; POPULATION; LINKAGE; POWER; TRAITS; LOCI AB Genome-wide association studies have opened a new era in the study of the genetic basis of common, multifactorial diseases and traits. Before the introduction of this approach only a handful of common genetic variants showed consistent association for any phenotype. Using genome-wide association, scores of novel and unsuspected loci have been discovered and later replicated for many complex traits. The principle is to genotype a dense set of common genetic variants across the genomes of individuals with phenotypic differences and examine whether genotype is associated with phenotype. Because the last common human ancestor was relatively recent and recombination events are concentrated in focal hotspots, most common variation in the human genome can be surveyed using a few hundred thousand variants acting as proxies for ungenotyped variants. Here, we describe the different steps of genome-wide association studies and use a recent study as example. C1 [Smith, J. Gustav] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Smith, JG (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. NR 76 TC 11 Z9 12 U1 3 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-246-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 573 BP 231 EP 258 DI 10.1007/978-1-60761-247-6_14 D2 10.1007/978-1-60761-247-6 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cardiac & Cardiovascular Systems SC Biochemistry & Molecular Biology; Cardiovascular System & Cardiology GA BMH93 UT WOS:000272402300014 PM 19763932 ER PT J AU Ademi, Z Liew, D Chew, D Conner, G Shiel, L Nelson, M Soman, A Steg, G Bhatt, DL Reid, C AF Ademi, Zanfina Liew, Danny Chew, Derek Conner, Greg Shiel, Louise Nelson, Mark Soman, Ash Steg, Gabriel Bhatt, Deepak L. Reid, Christopher CA REACH Registry Investigators TI Drug Treatment and Cost of Cardiovascular Disease in Australia SO CARDIOVASCULAR THERAPEUTICS LA English DT Article DE Average annual costs; Cardiovascular disease; Medicine ID TRANSIENT ISCHEMIC ATTACK; CORONARY-ARTERY-DISEASE; PLACEBO-CONTROLLED TRIAL; LOW-DOSE ASPIRIN; SECONDARY PREVENTION; RISK-FACTORS; REACH REGISTRY; DOUBLE-BLIND; ATHEROTHROMBOSIS; STROKE AB Australia's Pharmaceutical Benefits Scheme supports the use of effective drugs for the prevention and control of cardiovascular risk factors. However, there are little data available describing per person costs of medication in primary prevention and secondary prevention in the community. We aim to understand annual expenditure on cardiovascular medicines according to the level and extent of cardiovascular disease, using participants enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) registry. 2873 participants were recruited into the REACH registry through 273 Australian general practices. Cardiovascular medicines review was undertaken at baseline. Average weighted costs of medications were estimated using government-reimbursed prices. Annual costs were stratified by disease extent and location. The annual mean cost of pharmaceuticals per person was AU$1307. The average reported medicine use per person across all states and participants groups varied significantly. Participants with cerebrovascular or peripheral arterial disease were prescribed less cardiovascular medication than those with coronary artery disease (CAD) (mean number of drugs 3.5 vs. 4.5, P < 0.0001) and (3.6 vs. 4.5, P < 0.0001), while those with risk factor alone had the same medication use as those with CAD (mean number 4.5). Medication use was lower in Western Australia in comparison to eastern States. Participants with existing cerebrovascular disease and peripheral vascular disease receive less preventive therapy than those with CAD or even risk factors alone. This observation is consistent across all mainland states. Given the evidence of the effectiveness and cost-effectiveness of treating all types of vascular diseases, the present study suggests that there is scope to improve the treatment of these high-risk participants in Australia. C1 [Ademi, Zanfina; Shiel, Louise; Reid, Christopher] Monash Univ, Dept Epidemiol & Prevent Med, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. [Liew, Danny] Univ Melbourne, Dept Med, St Vincent Hosp, Melbourne, Vic 3010, Australia. [Chew, Derek] Flinders Med Ctr, Dept Cardiol, Adelaide, SA, Australia. [Nelson, Mark] Univ Tasmania, Menzies Res Inst, Hobart, Tas 7001, Australia. [Steg, Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Steg, Gabriel] AP HP, Paris, France. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ademi, Z (reprint author), Monash Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth & Prevent Med, Alfred Hosp, Commercial Rd, Melbourne, Vic 3004, Australia. EM Zanfina.Ademi@med.monash.edu.au OI Liew, Danny/0000-0002-0131-623X FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Australian Research Council [LP0775329]; Monash University FX The REACH registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH registry is endorsed by the World Heart Federation. A complete list of REACH investigators is accessible online at http://www.reachregistry.org. In addition, this work is supported in part by the Australian Research Council Linkage Project LP0775329. Support of this PhD work is provided by Monash University. NR 44 TC 12 Z9 12 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5914 J9 CARDIOVASC THER JI Cardiovasc. Ther. PY 2009 VL 27 IS 3 BP 164 EP 172 DI 10.1111/j.1755-5922.2009.00090.x PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 479TL UT WOS:000268683700003 PM 19689615 ER PT S AU Karha, J Bhatt, DL AF Karha, Juhana Bhatt, Deepak L. BE Saw, J TI Patient Selection for Carotid Stenting SO CAROTID ARTERY STENTING: THE BASICS SE Contemporary Cardiology LA English DT Article; Book Chapter DE Indications; Contraindications; Reimbursement; Training requirement; Credentialing ID TRANSIENT ISCHEMIC ATTACK; HEALTH-CARE PROFESSIONALS; SURGICAL-RISK PATIENTS; OF-NEUROLOGY AFFIRMS; ARTERY STENOSIS; SYMPTOMATIC PATIENTS; SURGERY-TRIAL; ENDARTERECTOMY; STROKE; PREVENTION AB The goal in treating carotid artery atherosclerotic disease is to reduce the risk of stroke. Three therapeutic options for management of carotid disease exist: medical therapy, carotid artery stenting, and carotid endarterectomy. Clinical and anatomic characteristics of the individual patient dictate which of these options should be chosen. This chapter will review the indications and contraindications to carotid artery stenting. C1 [Karha, Juhana] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, TIMI Grp, Boston, MA USA. RP Karha, J (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-313-8 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2009 BP 111 EP 120 DI 10.1007/978-1-60327-314-5_7 D2 10.1007/978-1-60327-314-5 PG 10 WC Cardiac & Cardiovascular Systems; Neurosciences SC Cardiovascular System & Cardiology; Neurosciences & Neurology GA BLF05 UT WOS:000270036200007 ER PT J AU Rexer, BN Engelman, JA Arteaga, CL AF Rexer, Brent N. Engelman, Jeffrey A. Arteaga, Carlos L. TI Overcoming resistance to tyrosine kinase inhibitors Lessons learned from cancer cells treated with EGFR antagonists SO CELL CYCLE LA English DT Article DE breast cancer; HER2; EGFR; tyrosine kinase inhibitors; TKI resistance; PI3K ID GROWTH-FACTOR RECEPTOR; HER2-OVEREXPRESSING BREAST-CANCER; LUNG-CANCER; TRASTUZUMAB RESISTANCE; ADJUVANT CHEMOTHERAPY; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; SOMATIC MUTATIONS; GENE MUTATION; GEFITINIB AB Tyrosine kinase inhibitors (TKIs) are effective anti-cancer therapies but resistance to these agents eventually develops. Several models of resistance to TKIs have been studied including resistance to EGFR inhibitors. Recent studies in EGFR-dependent A431 cells found upregulation of the IGF1R pathway as a mechanism to overcome blockade of EGFR. This was associated with amplification of IGF1R signaling and recovery of downstream PI3K-AKT activation. This work adds to a growing body of cell lines in culture that have provided insights into mechanisms of resistance that can be interrogated in primary tumors in patients. In this review, these model systems and their applicability to human cancers, as well as strategies to identify and overcome resistance to TKIs, are discussed. C1 [Arteaga, Carlos L.] Vanderbilt Univ, Sch Med, Breast Canc Res Program, Vanderbilt Ingram Comprehens Canc Ctr,Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Breast Canc Res Program, Vanderbilt Ingram Comprehens Canc Ctr,Dept Canc B, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Arteaga, CL (reprint author), Vanderbilt Univ, Sch Med, Breast Canc Res Program, Vanderbilt Ingram Comprehens Canc Ctr,Dept Med, 777 PRB,2220 Pierce Ave, Nashville, TN 37232 USA. EM carlos.arteaga@vanderbilt.edu FU NCI [R01 CA62212, R01 CA80195, T32 CA119910]; ACS Clinical Research Professorship [CRP-07-234]; Entertainment Industry Foundation; Breast Cancer Specialized Program of Research Excellence (SPORE [P50 CA98131]; Vanderbilt-Ingram Comprehensive Cancer Center [P30 CA68485]; NIH K08 [CA120060-01]; American Association for Cancer Research; DF/HCC Lung Cancer Specialized Program SPORE [P50 CA090578]; DF/HCC Gastrointestinal Cancer SPORE [P50 CA127003] FX Supported in part by NCI R01 CA62212 (C.L.A.), R01 CA80195 (C.L.A.), ACS Clinical Research Professorship Grant CRP-07-234 (C.L.A.), a grant from the Entertainment Industry Foundation (C.L.A.), NCI T32 CA119910 (B.N.R.), Breast Cancer Specialized Program of Research Excellence (SPORE) P50 CA98131, Vanderbilt-Ingram Comprehensive Cancer Center Support Grant P30 CA68485, NIH K08 grant CA120060-01 (J.A.E.), an American Association for Cancer Research Grant (J.A.E.), the DF/HCC Lung Cancer Specialized Program SPORE grant P50 CA090578 (J.A.E.), and the DF/HCC Gastrointestinal Cancer SPORE grant P50 CA127003 (J.A.E). NR 44 TC 49 Z9 49 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2009 VL 8 IS 1 BP 18 EP 22 DI 10.4161/cc.8.1.7324 PG 5 WC Cell Biology SC Cell Biology GA 390AW UT WOS:000262137700007 PM 19106609 ER PT J AU McKenna, ES Roberts, CWM AF McKenna, Elizabeth S. Roberts, Charles W. M. TI Epigenetics and cancer without genomic instability SO CELL CYCLE LA English DT Article DE genomic instability; epigenetics; chromatin remodeling; SWI/SNF; SNF5; INI1; BAF47; SMARCB1 ID ISLAND METHYLATOR PHENOTYPE; TUMOR-SUPPRESSOR GENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; RENAL MEDULLARY CARCINOMA; COLORECTAL-CANCER; CPG ISLAND; CHROMOSOMAL INSTABILITY; RHABDOID TUMOR; MICROSATELLITE INSTABILITY; SWI/SNF COMPLEX AB Genomic instability is often considered a hallmark of cancer. However, it remains unclear whether chromosomal disorganization is most frequently a cause or a consequence of tumorigenesis. The fact that subsets of many cancers lack chromosomal or micro-satellite instability argues against the hypothesis that genomic instability plays an essential role in the initiation and maintenance of oncogenesis. Cancer-specific, epigenetically-based changes in gene expression caused by abnormalities in DNA methylation, in histone modifications, and in nucleosome positioning are gaining recognition as driving events in tumorigenesis. But are these changes merely a small piece of the oncogenesis puzzle or could they be the major component, or even sufficient for cancer? Here we discuss evidence that the progression of aggressive cancers can be driven by epigenetic events without genomic instability. C1 [McKenna, Elizabeth S.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Dept Pediat Oncol,Div Hematol Oncol, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Dept Pediat Oncol,Div Hematol Oncol, Mayer Bldg,Room 657,44 Binney St, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu FU Garrett B. Smith Foundation; Claudia Adams Barr Foundation; Murphy Family Research Fund FX We thank Drs. David Pellman and Jennifer Perry for critical reading of the manuscript. CWMR gratefully acknowledges support from the Garrett B. Smith Foundation, the Claudia Adams Barr Foundation, and the Murphy Family Research Fund. NR 85 TC 35 Z9 35 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2009 VL 8 IS 1 BP 23 EP 26 DI 10.4161/cc.8.1.7290 PG 4 WC Cell Biology SC Cell Biology GA 390AW UT WOS:000262137700008 PM 19098432 ER PT J AU Macklis, JD AF Macklis, J. D. TI Molecular Development and Cellular Repair of Corticospinal Motor Neuron (and other Projection Neuron) Circuitry SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Macklis, J. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 223 EP 224 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800057 ER PT J AU Teng, YD Yu, D Benedict, DE Wilhelmsson, U Pekny, M AF Teng, Y. D. Yu, D. Benedict, D. E. Wilhelmsson, U. Pekny, M. TI Neural Stern Cell Engraftment and Reactive Astrogliosis Following SCI: A GFAP(-/-) Vimentin(-/-) Knockout Study SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Teng, Y. D.; Yu, D.; Benedict, D. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Teng, Y. D.; Yu, D.; Benedict, D. E.] Childrens Hosp, Boston, MA 02115 USA. [Teng, Y. D.; Yu, D.; Benedict, D. E.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Teng, Y. D.] VA Boston Healthcare Syst, Div SCI Res, Boston, MA USA. [Wilhelmsson, U.; Pekny, M.] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Ctr Brain Repair & Rehabil,Dept Clin Neurosci & R, Gothenburg, Sweden. NR 0 TC 3 Z9 3 U1 0 U2 3 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 237 EP 237 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800096 ER PT J AU Tye, CE Lorenz, RL Bartlett, JD AF Tye, Coralee E. Lorenz, Rachel L. Bartlett, John D. TI Lysosomal Protease Expression in Mature Enamel SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 9th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-08, 2007 CL Lakeland, TX DE Enamel; Proteases; Ameloblasts; Lysosome; Cathepsin ID CATHEPSIN-C GENE; RAT INCISOR; LOCALIZATION; AMELOGENESIS; AMELOBLASTS; MUTATIONS; PROTEINS; ORGAN AB The enamel matrix proteins ( amelogenin, enamelin and are degraded by matrix metalloproteinase-20 and kallikrein-4 during enamel development and enamel is virtually protein free. The precise mechanism removal and degradation of the enamel protein products from the matrix, however, remains poorly It has been proposed that receptor-mediated allows for the cleaved proteins to be removed the matrix during enamel formation and then transported the lysosome for further degradation. This study aims identify lysosomal proteases that are present in enamel organ. RNA from first molars of 11-daymice was collected and expression was initially assessed RT-PCR and then quantified by qPCR. The pattern of of selected proteases was assessed by staining of demineralized mouse incisors. With exception of cathepsin G, all lysosomal proteases were expressed in maturation-stage enamel organ. proteases included cathepsins B, D, F, H, K, L, O, S and Tripeptidyl peptidases I and II as well as dipeptidyl I, II, III and IV were also found to be expressed. staining confirmed that the ameloblasts express cathepsins L and S and peptidase II. Our results suggest that the ameloblasts are riched by a large number of lysosomal proteases at maturation that are likely involved in the degradation of the organic matrix. Copyright (C) 2008 S. Karger AG, Basel C1 [Bartlett, John D.] Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Bartlett, JD (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM jbartlett@forsyth.org FU NIDCR NIH HHS [R56 DE016276, R01 DE016276-03, DE016276, R01 DE016276] NR 20 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2009 VL 189 IS 1-4 BP 111 EP 114 DI 10.1159/000151431 PG 4 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 384VJ UT WOS:000261772000020 PM 18703868 ER PT J AU Wright, JT Hart, TC Hart, PS Simmons, D Suggs, C Daley, B Simmer, J Hu, J Bartlett, JD Li, Y Yuan, ZA Seow, WK Gibson, CW AF Wright, J. Timothy Hart, Thomas C. Hart, P. Suzanne Simmons, Darrin Suggs, Cynthia Daley, Bill Simmer, Jim Hu, Jan Bartlett, John D. Li, Yong Yuan, Zhi-An Seow, W. Kim Gibson, Carolyn W. TI Human and Mouse Enamel Phenotypes Resulting from Mutation or Altered Expression of AMEL, ENAM, MMP20 and KLK4 SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 9th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-08, 2007 CL Lakeland, TX DE Enamel; Amelogenesis imperfecta; Mouse; Human; Gene; Mutation ID DOMINANT AMELOGENESIS IMPERFECTA; MICE DISPLAY; GENE; NOMENCLATURE; DEFECTS; PROTEIN AB Amelogenesis imperfecta (AI) is caused by AMEL, ENAM, MMP20 and KLK4 gene mutations. Mice lacking expression of the AmelX, Enam and Mmp20 genes have been generated. These mouse models provide tools for understanding enamel formation and AI pathogenesis. This study describes the AI phenotypes and relates them to their mouse model counterparts. Human AI phenotypes were determined in a clinical population of AI families and published cases. Human and murine teeth were evaluated using light and electron microscopy. A total of 463 individuals from 54 families were evaluated and mutations in the AMEL, ENAM and KLK4 genes were identified. The majority of human mutations for genes coding enamel nonproteinase proteins (AMEL and ENAM) resulted in variable hypoplasia ranging from local pitting to a marked, generalized enamel thinning. Specific AMEL mutations were associated with abnormal mineralization and maturation defects. Amel and Enam null murine models displayed marked enamel hypoplasia and a complete loss of prism structure. Human mutations in genes coding for the enamel proteinases (MMP20 and KLK4) cause variable degrees of hypomineralization. The murine Mmp20 null mouse exhibits both hypoplastic and hypomineralized defects. The currently available Amel and Enam mouse models for AI exhibit enamel phenotypes (hypoplastic) that are generally similar to those seen in humans. Mmp20 null mice have a greater degree of hypoplasia than humans with MMP20 mutations. Mice lacking expression of the currently known genes associated with the human AI conditions provide useful models for understanding the pathogenesis of these conditions. Copyright (C) 2008 S. Karger AG, Basel C1 [Wright, J. Timothy] Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC 27599 USA. [Hart, Thomas C.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Hart, P. Suzanne] NHGRI, NIH, Human Genome Project, Bethesda, MD 20892 USA. [Simmer, Jim; Hu, Jan] Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Bartlett, John D.] Forsyth Inst, Boston, MA USA. [Li, Yong; Yuan, Zhi-An; Gibson, Carolyn W.] Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Seow, W. Kim] Univ Queensland, Dept Dent, Brisbane, Qld, Australia. RP Wright, JT (reprint author), Univ N Carolina, Sch Dent, Dept Pediat Dent, Brauer Hall 7450, Chapel Hill, NC 27599 USA. EM tim_wright@dentistry.unc.edu RI Seow, W. Kim/F-2765-2010; Seow, W. K./F-7314-2010; OI Seow, Wan Kim/0000-0002-7876-4524 FU NIDCR NIH HHS [R01 DE011301, DE011089, DE01627, DE11301, DE12879, R01 DE011089, R01 DE011089-11, R01 DE011301-09, R01 DE012879, R01 DE012879-05, R01 DE016276, R01 DE016276-04, R29 DE011301, R56 DE011301] NR 24 TC 46 Z9 50 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2009 VL 189 IS 1-4 BP 224 EP 229 DI 10.1159/000151378 PG 6 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 384VJ UT WOS:000261772000039 PM 18714142 ER PT J AU Tabassam, FH Graham, DY Yamaoka, Y AF Tabassam, Fazal H. Graham, David Y. Yamaoka, Yoshio TI Helicobacter pylori activate epidermal growth factor receptor- and phosphatidylinositol 3-OH kinase-dependent Akt and glycogen synthase kinase 3 beta phosphorylation SO CELLULAR MICROBIOLOGY LA English DT Article ID GASTRIC EPITHELIAL-CELLS; NF-KAPPA-B; MUCOSAL INTERLEUKIN-8 PRODUCTION; PROMOTER ACTIVATION; DOWN-REGULATION; CANCER CELLS; PROTEIN; PATHWAY; OIPA; CHEMORESISTANCE AB The signalling pathways leading to the development of Helicobacter pylori-induced gastric cancer remain poorly understood. We tested the hypothesis that H. pylori infections involve the activation of Akt signalling in human gastric epithelial cancer cells. Immunoblot, immunofluorescence and kinase assays show that H. pylori infection of gastric epithelial cells induced phosphorylation of Akt at Ser 473 and Thr 308. Mutations in the H. pylori virulence factor OipA dramatically reduced phosphorylation of Ser 473, while the cag pathogenicity island mutants predominantly inhibited phosphorylation of Thr 308. As the downstream of Akt activation, H. pylori infection inactivated the inactivation of glycogen synthase kinase 3 beta at Ser 9 by its phosphorylation. As the upstream of Akt activation, H. pylori infection activated epidermal growth factor receptor (EGFR) at Tyr 992, phosphatidylinositol 3-OH kinase (PI3K) p85 subunit and PI3K-dependent kinase 1 at Ser 241. Pharmacologic inhibitors of PI3K or mitogen-activated protein kinase kinase (MEK), Akt knock-down and EGFR knock-down showed that H. pylori infection induced the activation of EGFR -> PI3K -> PI3K-dependent kinase 1 -> Akt -> extracellular signal-regulated kinase signalling pathways, the inactivation of glycogen synthase kinase 3 beta and interleukin-8 production. The combined functions of cag pathogenicity island and OipA were necessary and sufficient for full activation of signalling at each level. We propose activation of these pathways as a novel mechanism for H. pylori-mediated carcinogenesis. C1 [Yamaoka, Yoshio] Michael DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Yamaoka, Y (reprint author), Michael DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs [DK56338]; NIH [DK 62813] FX This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, by Public Health Service Grant DK56338 that funds the Texas Medical Center Digestive Diseases Center. The project described was also supported by Grant Number DK 62813 from NIH. Their contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH. NR 49 TC 53 Z9 53 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JAN PY 2009 VL 11 IS 1 BP 70 EP 82 DI 10.1111/j.1462-5822.2008.01237.x PG 13 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 390FQ UT WOS:000262150100006 PM 18782353 ER PT J AU Zimmerman, B Simaan, M Lee, MH Luttrell, LM Laporte, SA AF Zimmerman, Brandon Simaan, May Lee, Mi-Hye Luttrell, Louis M. Laporte, Stephane A. TI c-Src-mediated phosphorylation of AP-2 reveals a general mechanism for receptors internalizing through the clathrin pathway SO CELLULAR SIGNALLING LA English DT Article DE G protein-coupled receptors; AT1R; beta arrestins; c-Src; AP-2; Clathrin; EGF receptor ID PROTEIN-COUPLED RECEPTORS; INTRACELLULAR TRAFFICKING PATHWAYS; AGONIST-INDUCED INTERNALIZATION; ACTIVATING-FACTOR RECEPTOR; GROWTH-FACTOR RECEPTOR; II TYPE-1 RECEPTOR; TYROSINE PHOSPHORYLATION; BETA-ARRESTIN; ADAPTER PROTEIN-2; MU-2 SUBUNIT AB Clathrin-mediated endocytosis is a complex process regulated at many different levels. We showed previously that activation of the angiotensin type 1 receptor (AT1R), which belongs to the G protein-coupled receptor (GPCR) family, leads to c-Src-dependent tyrosine phosphorylation of beta 2-adaptin, a subunit of the clathrin adaptor AP-2. The phosphorylation of beta 2-adaptin on tyrosine residue 737 (Y737) negatively regulates its interaction with beta arrestin, another important clathrin adaptor for GPCR internalization. Here we sought to determine whether AP-2 phosphorylation represents a general mechanism for different receptors internalizing through the clathrin pathway. Using a specifically designed antibody against the phosphorylated form of Y737 on beta 2-adaptin, we demonstrate that this residue is phosphorylated by AT1R in different cell types like HEK293, COS-7 and vascular smooth muscle cells. Using RNA interference approaches, we reveal that this agonist-mediated event is both beta arrestin- and c-Src-dependent, and that it occurs at the plasma membrane in clathrin-coated vesicles (CCVs). We further show that this is not only a common event employed by other GPCRs like the beta 2-adrenergic, vasopressin V2, bradykinin type 2, platelet-activating factor and endothelin A receptors but that the epidermal growth factor receptor is capable of eliciting the phosphorylation of AP-2 in CCVs. Our results imply that tyrosine phosphorylation of Y737 on beta 2-adaptin is a common regulatory mechanism employed by different receptors undergoing clathrin-dependent endocytosis, and suggest a wider function for this event than originally anticipated. (C) 2008 Elsevier Inc. All rights reserved. C1 [Zimmerman, Brandon; Simaan, May; Laporte, Stephane A.] McGill Univ, Royal Victoria Hosp, Dept Med, Hormones & Canc Res Unit,Hlth Ctr,Res Inst, Montreal, PQ H3A 1A1, Canada. [Zimmerman, Brandon; Laporte, Stephane A.] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada. [Lee, Mi-Hye; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lee, Mi-Hye; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Lee, Mi-Hye; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Laporte, SA (reprint author), McGill Univ, Royal Victoria Hosp, Dept Med, Hormones & Canc Res Unit,Hlth Ctr,Res Inst, 687 Pine Ave W,Room H7-64, Montreal, PQ H3A 1A1, Canada. EM stephane.laporte@mcgill.ca RI Laporte, Stephane/F-3282-2012 FU Canadian Institutes of Health Research (CIHR); CIHR; McGill University Health Center Research Institute (MUHC-RI); Fonds de la Recherche en Sante du Quebec (FRSQ) FX We thank Drs Witold A. Neugebauer and Emanuel Escher (Universite de Sherbrooke) for peptide synthesis and the Angiotensin II analog. This work was supported by a Canadian Institutes of Health Research (CIHR) Operating Grant and a CIHR Confocal Maintenance Grant to S.A.L. B.Z. holds a CIHR studentship award. M.S. holds a Fellowship award from the McGill University Health Center Research Institute (MUHC-RI), which is a recognized Fonds de la Recherche en Sante du Quebec (FRSQ) supported Institute. SAL holds a Canada Research Chair in Molecular Endocrinology. NR 41 TC 30 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2009 VL 21 IS 1 BP 103 EP 110 DI 10.1016/j.cellsig.2008.09.013 PG 8 WC Cell Biology SC Cell Biology GA 389AB UT WOS:000262060900013 PM 18938240 ER PT J AU Lerner, A Bagic, A Hanakawa, T Boudreau, EA Pagan, F Mari, Z Bara-Jimenez, W Aksu, M Sato, S Murphy, DL Hallett, M AF Lerner, Alicja Bagic, Anto Hanakawa, Takashi Boudreau, Eilis A. Pagan, Fernando Mari, Zoltan Bara-Jimenez, William Aksu, Murat Sato, Susumu Murphy, Dennis L. Hallett, Mark TI Involvement of Insula and Cingulate Cortices in Control and Suppression of Natural Urges SO CEREBRAL CORTEX LA English DT Article ID EVENT-RELATED FMRI; OBSESSIVE-COMPULSIVE DISORDER; OLD-WORLD MONKEY; STOP-SIGNAL TASK; RESPONSE-INHIBITION; FUNCTIONAL MRI; PHYSIOLOGICAL CONDITION; VOLUNTARY SUPPRESSION; TOURETTE-SYNDROME; BRAIN RESPONSES AB The physiology of control and suppression of natural urges is not well understood. We used [(15)O]H(2)O positron-emission tomography imaging to identify neural circuits involved in suppression of spontaneous blinking as a model of normal urges. Suppression of blinking was associated with prominent activation of bilateral insular-claustrum regions, right more than left; activation was also found in bilateral anterior cingulate cortex (ACC), supplementary motor areas, and the face area of the primary motor cortex bilaterally. These results suggest a central role for the insula possibly together with ACC in suppression of blinking. C1 [Lerner, Alicja; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Bagic, Anto] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Hanakawa, Takashi] Natl Ctr Neurol & Psychiat, Dept Cort Funct Disorder, Tokyo 1878502, Japan. [Boudreau, Eilis A.] Portland VA Med Ctr, Hlth Sci Res & Dev Program, Portland, OR 97239 USA. [Pagan, Fernando] Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA. [Mari, Zoltan] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Bara-Jimenez, William] Bethesda Neurosci Clin, Bethesda, MD 20885 USA. [Aksu, Murat] Erciyes Univ, Fac Med, Dept Neurol, TR-38039 Kayseri, Turkey. [Sato, Susumu] Natl Inst Neurol Disorders & Stroke, EEG Sect, Bethesda, MD 20892 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Lerner, A (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM lernera@mail.nih.gov FU Intramural Research Programs of the National Institute of Neurological Disorders and Stroke; National Institute of Mental Health with the National Institutes of Health FX Intramural Research Programs of the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health with the National Institutes of Health. NR 69 TC 43 Z9 46 U1 4 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2009 VL 19 IS 1 BP 218 EP 223 DI 10.1093/cercor/bhn074 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 383ND UT WOS:000261679400021 PM 18469316 ER PT J AU Pandhi, N Smith, MA Kind, AJH Frytak, JR Finch, MD AF Pandhi, Nancy Smith, Maureen A. Kind, Amy J. H. Frytak, Jennifer R. Finch, Michael D. TI The Quality of Diabetes Care following Hospitalization for Ischemic Stroke SO CEREBROVASCULAR DISEASES LA English DT Article DE Cerebrovascular accident; Diabetes mellitus; Quality of care ID HEALTH-CARE; RACIAL DISPARITIES; UNITED-STATES; RISK-FACTORS; PREVENTION; HISPANICS; AMERICAN; VETERANS; DISEASE; BLACKS AB Background: Follow-up is critically important for stroke survivors with diabetes, yet there is limited research about the quality of diabetes care that these patients receive. We investigated performance on diabetes quality of care indicators for stroke survivors overall and by race. Methods: Claims data was extracted for 1,460 Medicare beneficiaries with preexisting diabetes who survived hospitalization for acute ischemic stroke in 2000. Adjusted probabilities of receiving HbA1c, LDL and dilated eye exams were estimated using logistic regression. Results: 53% had a dilated eye exam, 60% received an LDL check, 73% percent had their HbA1c checked at least once and only 51% received two or more HbA1c checks. In the unadjusted results, blacks were significantly less likely than whites to receive these tests. Conclusions: Care of stroke survivors, particularly blacks, shows gaps according to guidelines. Copyright (C) 2009 S. Karger AG, Basel C1 [Pandhi, Nancy; Smith, Maureen A.; Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Pandhi, Nancy] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. [Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Geriatr, Madison, WI USA. [Kind, Amy J. H.] William S Middleton Mem Vet Adm Med Ctr, US Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Frytak, Jennifer R.] i3 Innovus, Minneapolis, MN USA. [Finch, Michael D.] Finch & King Inc, Minneapolis, MN USA. RP Pandhi, N (reprint author), 557 WARF Off Bldg,610 Walnut St, Madison, WI 53726 USA. EM nancy.pandhi@fammed.wisc.edu FU National Institute of Aging [R01-AG19747]; Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR) funded through an NIH [1 UL1 RR025011] FX This study was supported by a grant (R01-AG19747) from the National Institute of Aging (Principal Investigator: Maureen Smith, MD, PhD). This project was also supported by the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR) funded through an NIH Clinical and Translational Science Award (CTSA), grant No. 1 UL1 RR025011. NR 28 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2009 VL 27 IS 3 BP 235 EP 240 DI 10.1159/000196821 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 409VN UT WOS:000263534000005 PM 19176956 ER PT B AU Batista, D Korzenik, J AF Batista, Daisy Korzenik, Joshua BA Scherl, EJ Dubinsky, MC BF Scherl, EJ Dubinsky, MC TI INFLAMMATORY BOWEL DISEASE IN THE DEVELOPING WORLD A RAPID EVOLUTION OF GLOBAL EPIDEMIOLOGY SO CHANGING WORLD OF INFLAMMATORY BOWEL DISEASE: IMPACT OF GENERATION, GENDER, AND GLOBAL TRENDS LA English DT Article; Book Chapter ID FORMULA-FED INFANTS; ULCERATIVE-COLITIS; CROHNS-DISEASE; CHINESE POPULATION; OLMSTED COUNTY; RISK-FACTORS; INDETERMINATE COLITIS; SOUTHEASTERN NORWAY; JEWISH POPULATION; DIETARY FACTORS C1 [Batista, Daisy; Korzenik, Joshua] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Crohns & Colitis Ctr, Boston, MA 02115 USA. RP Batista, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Crohns & Colitis Ctr, Boston, MA 02115 USA. NR 109 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-841-8 PY 2009 BP 17 EP 30 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BLV80 UT WOS:000271190200002 ER PT J AU Caravan, P Das, B Deng, Q Dumas, S Jacques, V Koerner, SK Kolodziej, A Looby, RJ Sun, WC Zhang, ZD AF Caravan, Peter Das, Biplab Deng, Qing Dumas, Stephane Jacques, Vincent Koerner, Steffi K. Kolodziej, Andrew Looby, Richard J. Sun, Wei-Chuan Zhang, Zhaoda TI A lysine walk to high relaxivity collagen-targeted MRI contrast agents SO CHEMICAL COMMUNICATIONS LA English DT Article ID THROMBUS; MICE AB A strategy for preparing peptide-based magnetic resonance contrast agents with multiple gadolinium chelates is described. C1 [Caravan, Peter] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Das, Biplab; Deng, Qing; Dumas, Stephane; Jacques, Vincent; Koerner, Steffi K.; Kolodziej, Andrew; Looby, Richard J.; Sun, Wei-Chuan; Zhang, Zhaoda] Epix Pharmaceut, Lexington, MA 02140 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu NR 16 TC 17 Z9 17 U1 0 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2009 IS 4 BP 430 EP 432 DI 10.1039/b819098d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 393UI UT WOS:000262398500013 PM 19137175 ER PT J AU Hilderbrand, SA Shao, FW Salthouse, C Mahmood, U Weissleder, R AF Hilderbrand, Scott A. Shao, Fangwei Salthouse, Christopher Mahmood, Umar Weissleder, Ralph TI Upconverting luminescent nanomaterials: application to in vivo bioimaging SO CHEMICAL COMMUNICATIONS LA English DT Article ID UP-CONVERSION EMISSION; QUANTUM DOTS; SURFACE MODIFICATION; NANOCRYSTALS; FLUORESCENCE; NANOPHOSPHORS; NANOPARTICLES; CYTOTOXICITY; CERIUM AB In this report, the development of multi-channel anti-Stokes luminescent Y(2)O(3) nanoparticles for application to in vivo upconversion imaging is detailed. C1 [Hilderbrand, Scott A.; Shao, Fangwei; Salthouse, Christopher; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Hilderbrand, Scott A.; Shao, Fangwei; Salthouse, Christopher; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. [Mahmood, Umar] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hilderbrand, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Room 6229149,13th St, Charlestown, MA 02129 USA. EM Scott_Hilderbrand@hms.harvard.edu RI Shao, Fangwei/B-7026-2011 FU NIH [U01-HL080731, R01-EB001872, U54-CA119349, P50-CA86355, R24-CA92782, T32-EB002102] FX This research was supported in part by NIH grants U01-HL080731, R01-EB001872, U54-CA119349, P50-CA86355, R24-CA92782, and T32-EB002102. NR 25 TC 172 Z9 174 U1 5 U2 85 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2009 IS 28 BP 4188 EP 4190 DI 10.1039/b905927j PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 468HN UT WOS:000267808000007 PM 19585016 ER PT J AU Garanger, E Hilderbrand, SA Blois, JT Sosnovik, DE Weissleder, R Josephson, L AF Garanger, Elisabeth Hilderbrand, Scott A. Blois, Joseph T. Sosnovik, David E. Weissleder, Ralph Josephson, Lee TI A DNA-binding Gd chelate for the detection of cell death by MRI SO CHEMICAL COMMUNICATIONS LA English DT Article ID THIAZOLE ORANGE; ANNEXIN-V; IN-VIVO; APOPTOSIS; DYE AB GadoTO, a MR contrast agent for the detection of cell death, consists of a nucleic acid-binding fluorophore attached to a gadolinium chelate. C1 [Garanger, Elisabeth; Hilderbrand, Scott A.; Blois, Joseph T.; Sosnovik, David E.; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. EM ljosephson@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL093038]; NIBIB NIH HHS [R01 EB004472, R01 EB000662, R01 EB000662-04, R01 EB004472-04, R01 EB009691, R01 EB011996] NR 13 TC 18 Z9 18 U1 1 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2009 IS 29 BP 4444 EP 4446 DI 10.1039/b907375b PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 471TN UT WOS:000268081300033 PM 19597620 ER PT J AU Kuschner, WG Gruenewald, DA Clum, N Beal, A Ezeji-Okoye, SC AF Kuschner, Ware G. Gruenewald, David A. Clum, Nancy Beal, Alice Ezeji-Okoye, Stephen C. TI Implementation of ICU Palliative Care Guidelines and Procedures A Quality Improvement Initiative Following an Investigation of Alleged Euthanasia SO CHEST LA English DT Article DE end-of-life care; guidelines; ICU; life support; palliative care ID LIFE-SUSTAINING TREATMENT; INTENSIVE-CARE; END; UNIT; WITHDRAWAL; SUPPORT; STATEMENT; DEATH AB Ethical conflicts are commonly encountered in the course of delivering end-of-life care in the ICU. Some ethical concerns have legal dimensions, including concerns about inappropriate hastening of death. Despite these concerns, many lCUs do not have explicit policies and procedures for withdrawal of life-sustaining treatments. We, describe a US Office of Inspector General (OIG) investigation of end-of-life care practices in our ICU. The investigation focused on care delivered to four critically ill patients with terminal diseases and an ICU nurse's concern that the patients had been subjected to euthanasia. The OIG investigation also assessed the validity of allegations that patient flow in and out of our ICU wits inappropriately influenced by, scheduled surgeries and that end-of-life care policies in our ICU were not clear. Although the investigation did not substantiate the allegations of euthanasia or inappropriate ICU patient flow, it did find that the policies that discuss end-of-life care issues were not clear and allowed for wide-ranging interpretations. Acting on the OIG recommendations, we developed a quality improvement initiative addressing end-of-life care in our ICU, intended to enhance communication and understanding about palliative care practices in our ICU, to prevent ethical conflicts surrounding end-of-life care, and to improve patient care. The initiative included the introduction of newly developed ICU comfort care guidelines, a physician order set, and a physician template note. Additionally, we implemented an educational program for ICU staff. Staff feedback regarding the initiative has been highly favorable, and the nurse whose concerns led to the investigation was satisfied not only with the investigation but also the policies and procedures that were subsequently introduced in our ICU. (CHEST 2009; 135:26-32) C1 [Kuschner, Ware G.] Palo Alto Hlth Care Syst, US Dept Vet Affairs, Pulm & Crit Care Med Sect, Med Serv, Palo Alto, CA 94304 USA. [Gruenewald, David A.] Puget Sound Hlth Care Syst, US Dept Vet Affairs, Geriatr & Extended Care Serv, Seattle, WA USA. [Beal, Alice] New York Harbor Hlth Care Syst, US Dept Vet Affairs, Med Serv, Brooklyn, NY USA. RP Kuschner, WG (reprint author), Palo Alto Hlth Care Syst, US Dept Vet Affairs, Pulm & Crit Care Med Sect, Med Serv, 3801 Miranda Ave,Mail Code 111P, Palo Alto, CA 94304 USA. EM ware.kuschnermd@ca.gov NR 26 TC 10 Z9 13 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2009 VL 135 IS 1 BP 26 EP 32 DI 10.1378/chest.08-1685 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 392LN UT WOS:000262304300008 PM 19136403 ER PT J AU Greinix, HT Antin, JH AF Greinix, Hildegard T. Antin, Joseph H. BE Vogelsang, GB Pavletic, SZ TI SALVAGE THERAPY IN CHRONIC GRAFT VERSUS HOST DISEASE SO CHRONIC GRAFT VERSUS HOST DISEASE: INTERDISCIPLINARY MANAGEMENT LA English DT Article; Book Chapter ID TOTAL-LYMPHOID IRRADIATION; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; STEROID-REFRACTORY ACUTE; RECEPTOR FUSION PROTEIN; RESISTANT CHRONIC GVHD; EXTRACORPOREAL PHOTOCHEMOTHERAPY; MYCOPHENOLATE-MOFETIL; PUVA THERAPY; IMMUNOSUPPRESSIVE THERAPY C1 [Greinix, Hildegard T.] Med Univ Vienna, Vienna, Austria. [Antin, Joseph H.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Greinix, HT (reprint author), Med Univ Vienna, Vienna, Austria. NR 98 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88423-5 PY 2009 BP 134 EP 145 DI 10.1017/CBO9780511576751.014 D2 10.1017/CBO9780511576751 PG 12 WC Transplantation SC Transplantation GA BDG89 UT WOS:000313180800014 ER PT J AU Cutler, C AF Cutler, Corey BE Vogelsang, GB Pavletic, SZ TI HEMATOLOGIC COMPLICATIONS OF CHRONIC GRAFT VERSUS HOST DISEASE SO CHRONIC GRAFT VERSUS HOST DISEASE: INTERDISCIPLINARY MANAGEMENT LA English DT Article; Book Chapter ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; HEMOLYTIC-ANEMIA; EOSINOPHIL INFILTRATION; THROMBOCYTOPENIA; PATIENT; FASCIITIS; RITUXIMAB; APLASIA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Cutler, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St, Boston, MA 02115 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88423-5 PY 2009 BP 238 EP 242 DI 10.1017/CBO9780511576751.023 D2 10.1017/CBO9780511576751 PG 5 WC Transplantation SC Transplantation GA BDG89 UT WOS:000313180800023 ER PT S AU Drummond, I AF Drummond, Iain BE King, SM Pazour, GJ TI Studying Cilia in Zebrafish SO CILIA: MODEL ORGANISMS AND INTRAFLAGELLAR TRANSPORT SE Methods in Cell Biology LA English DT Review; Book Chapter ID MUTATIONS AFFECTING DEVELOPMENT; POLYCYSTIC KIDNEY-DISEASE; ZINC-FINGER NUCLEASES; INTRAFLAGELLAR TRANSPORT; KUPFFERS VESICLE; PRONEPHROS; GENES; DIFFERENTIATION; MOTILITY; BRAIN AB Zebrafish are ideally suited for analysis of genes required for ciliogenesis and cilia function. Combining genetic manipulation with high-quality in vivo imaging, zebrafish embryos provide a high-throughput system for annotation of the cilia proteome. The specific advantages of the system are the availability of cilia mutants, the ability to target genes of unknown function using antisense methods, the feasibility of observing cilia in living embryos, and the ability to image fixed cilia in wholemount at high resolution. Techniques are described for analysis of mutants, gene knockdown using antisense morpholino oligos, visualizing cilia and cilia orientation in wholemount zebrafish embryos, cilia imaging by high-speed video, and electron microscopy of zebrafish cilia. C1 [Drummond, Iain] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Drummond, Iain] Harvard Univ, Sch Med, Dept Genet, Charlestown, MA 02129 USA. [Drummond, Iain] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Drummond, I (reprint author), Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK070263, DK053093] NR 30 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-381377-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2009 VL 93 BP 197 EP + DI 10.1016/S0091-679X(08)93011-9 PG 22 WC Cell Biology SC Cell Biology GA BMI30 UT WOS:000272433900012 PM 20409819 ER PT S AU LaCount, LT Napadow, V Kuo, B Park, K Kim, J Brown, EN Barbieri, R AF LaCount, L. T. Napadow, V. Kuo, B. Park, K. Kim, J. Brown, E. N. Barbieri, R. BE Murray, A TI Dynamic Cardiovagal Response to Motion Sickness: A Point-Process Heart Rate Variability Study SO CINC: 2009 36TH ANNUAL COMPUTERS IN CARDIOLOGY CONFERENCE SE Computers in Cardiology Series LA English DT Proceedings Paper CT 36th Annual Computers in Cardiology Conference (CinC 2009) CY SEP 13-16, 2009 CL Pk City, UT SP EMB, IEEE, Medtron, CareFus, Biosense Webster, Mortara Instrument, Vitamin Water, Coca-Cola, IBM, GE Healthcare, Forest Pharmaceut Inc, St Jude Med, IOP Publishing, Zoll, Philips Healthcare, SCI - Univ Utah ID COMPONENTS; DISCOMFORT; MODEL AB A visual display of stripes was used to examine cardiovagal response to motion sickness. Heart rate variability (HRV) was investigated using dynamic methods to discern instantaneous fluctuations in reaction to stimulus and perception-based events. A novel point process adaptive recursive algorithm was applied to the R-R series to compute instantaneous heart rate. HRV, and high frequency (HF) power as a marker of vagal activity. Results show interesting dynamic trends in each of the considered subjects. HF power averaged across ten subjects indicates a significant decrease 20s to 60s following the transition from "no nausea" to "mild." Conversely, right before "strong" nausea, the group average shows a transient trending increase in HF power. Findings confirm gradual sympathetic activation with increasing nausea, and further evidence transitory increases in vagal tone before flushes of strong nausea. C1 [LaCount, L. T.] MGH, Martinos Ctr Biomed Imaging, CNY 149,13th St, Charlestown, MA 02129 USA. [Brown, E. N.; Barbieri, R.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. [Brown, E. N.; Barbieri, R.] MIT, Dept Brain & Cognit Sci, Boston, MA USA. [LaCount, L. T.; Napadow, V.; Park, K.; Kim, J.] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Napadow, V.] Logan Coll Chiroprac, Dept Radiol, Chesterfield, MO USA. [Kuo, B.] Massachusetts Gen Hosp, Harvard Med Sch, Gastroenterol Unit, Boston, MA USA. [Park, K.; Kim, J.] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. RP LaCount, LT (reprint author), MGH, Martinos Ctr Biomed Imaging, CNY 149,13th St, Charlestown, MA 02129 USA. OI Barbieri, Riccardo/0000-0001-9381-3833 FU NIH [RO1-HL084502, ROI-DAOI5644, DPI-0D003646, KOI-AT002166, POI-AT002048, F05-AT003770, K23-DK069614]; National Center for Complementary and Alternative Medicine [P41RRI4075, CRC 1 ULI RR025758-01]; Mental lliness and Neuroscience Discovery (MIND) Institute; International Foundation of Functional GI Disorders; Institute of Information Technology Advancement, Korea [IITA-2008-CI090-0801-0002] FX We would like to thank NIH for funding support (RB: RO1-HL084502; EB: ROI-DAOI5644 and DPI-0D003646; VN: KOI-AT002166, POI-AT002048; KP: F05-AT003770; BK: K23-DK069614), the National Center for Complementary and Alternative Medicine (P41RRI4075; CRC 1 ULI RR025758-01), the Mental lliness and Neuroscience Discovery (MIND) Institute, and the International Foundation of Functional GI Disorders. Dr. Park was also supported by the Institute of Information Technology Advancement, Korea IITA-2008-(CI090-0801-0002). NR 16 TC 13 Z9 13 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 978-1-4244-7281-9 J9 COMPUT CARDIOL PY 2009 BP 49 EP + PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA BPM81 UT WOS:000279344300013 ER PT S AU Syed, Z Scirica, BM Stultz, CM Guttag, JV AF Syed, Z. Scirica, B. M. Stultz, C. M. Guttag, J. V. BE Murray, A TI Electrocardiographic Prediction of Arrhythmias SO CINC: 2009 36TH ANNUAL COMPUTERS IN CARDIOLOGY CONFERENCE SE Computers in Cardiology Series LA English DT Proceedings Paper CT 36th Annual Computers in Cardiology Conference (CinC 2009) CY SEP 13-16, 2009 CL Pk City, UT SP EMB, IEEE, Medtron, CareFus, Biosense Webster, Mortara Instrument, Vitamin Water, Coca-Cola, IBM, GE Healthcare, Forest Pharmaceut Inc, St Jude Med, IOP Publishing, Zoll, Philips Healthcare, SCI - Univ Utah ID ACUTE CORONARY SYNDROMES; VARIABILITY AB Information in electrocardiographic: (ECG) signals is widely believed to have value in the short-term prediction of arrhythmias. This study evaluates the use of morphologic variability (MV), a recently proposed metric measuring subtle variability in the shape of ECG signals over long periods, to risk stratify patients for arrhythmia following non-ST-elevation acute coronary syndrome (NSTEACS). We assessed the relationship between MV and the composite occurrence of ventricular tachycardia and cardiac pause (150 events) in 2302 patients admitted post-NSTEACS. On univariate analysis, high MY was strongly associated with the short-term occurrence of arrhythmias (HR 2.02; 95% CI 1.42-2.87; p<0.001). The relationship between (1411 and arrhythmias was consistent even after adjusting for other risk variables (adjusted HR 2.04; 95% CI 1.37 - 3.03; p<0.001). Our results suggest that MV may be a clinically useful tool for identifying patients at an increased short-term risk of serious arrhythmias in the setting of NSTEACS. C1 [Syed, Z.] Univ Michigan, Ann Arbor, MI 48109 USA. [Scirica, B. M.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA. [Stultz, C. M.; Guttag, J. V.] MIT, Cambridge, MA USA. RP Syed, Z (reprint author), Univ Michigan, Ann Arbor, MI 48109 USA. EM zhs@eecs.umich.edu FU Integration of Medicine and Innovative Technology (CIMIT); Harvard-MIT Division of Health Sciences and Technology (HST); Industrial Technology Research Institute (ITRI); CV Therapeutics FX This work was supported by the Center for Integration of Medicine and Innovative Technology (CIMIT), the Harvard-MIT Division of Health Sciences and Technology (HST), and the Industrial Technology Research Institute (ITRI). The MERLIN trial was supported by CV Therapeutics. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 978-1-4244-7281-9 J9 COMPUT CARDIOL PY 2009 BP 565 EP + PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA BPM81 UT WOS:000279344300142 ER PT J AU Wu, MT Su, MYM Huang, YL Chiou, KR Yang, PC Pan, HB Reese, TG Wedeen, VJ Tseng, WYI AF Wu, Ming-Ting Su, Mao-Yuan M. Huang, Yi-Luan Chiou, Kuan-Rau Yang, Pinchen Pan, Huay-Ben Reese, Timothy G. Wedeen, Van J. Tseng, Wen-Yih I. TI Sequential Changes of Myocardial Microstructure in Patients Postmyocardial Infarction by Diffusion-Tensor Cardiac MR Correlation With Left Ventricular Structure and Function SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE imaging; magnetic resonance imaging; myocardial infarction; remodeling ID MAGNETIC-RESONANCE; WATER DIFFUSION; IN-VIVO; ARCHITECTURE; RAT; DYSFUNCTION; ANISOTROPY; MYOCYTES; MODELS; MOTION AB Background-We used diffusion-tensor cardiac MR to investigate myocardial microstructure changes, including tissue integrity (mean diffusivity [MD], fractional anisotropy) and fiber architecture (helix angles) in patients with recent myocardial infarction (MI). This study aimed to investigate the sequential changes of myocardial microstructure and its relationships with changes of macrostructure and function of the left ventricle post-MI. Methods and Results-Seventeen patients (age, 55.1 +/- 11.5 years; all men) participated in the follow-up study. Diffusion-tensor cardiac MR, cine gradient echo for left ventricle function. and late gadolinium enhancement for viability were measured from recent to chronic MI (median interval, 191 days). When compared with the remote zone, the infarct-adjacent zone showed overall increase of MID (2-way MANOVA. F(1.16)=36.3; P<0.001), decrease of fractional anisotropy (F(1.16)=5.8. P=0.029), and decrease of mean helix angles (F(1.16)=62.0, P<0.001). From recent to chronic MI. there was overall sequential decrease of MD (F(1.16) =22.6; P<0.001) and increase of fractional anisotropy,16 (F(1.16)=7.8; P=0.013). Multiple linear regression showed that the improvement of wall thickening in the infarct-adjacent zone correlated with sequential decrease of MID in the infarct-adjacent zone (r=-0.70-, P=0.002) and increase of mean helix angles (ie. more right-handed helical myofiber reorientation, predominantly subendocardial location) in the remote zone 0=0.60; P=0.011). Likewise, wall thickening in the remote zone correlated with MD in the remote zone 0-0.72; P=0.001) and mean helix angles in the infarct-adjacent zone (r=0.72; P=0.001). Conclusion-Diffusion-tensor cardiac MR suggests that sequential zonal improvement of tissue integrity and fiber architecture remodeling both associate with sequential recovery of zonal wall thickening of the left ventricle from recent to chronic MI. (Circ Cardiovasc Imaging. 2009;2:32-40.) C1 [Wu, Ming-Ting] Kaohsiung Vet Gen Hosp, Dept Radiol, Sect Thorac & Circulat Imaging, Kaohsiung 813, Taiwan. [Wu, Ming-Ting; Huang, Yi-Luan; Chiou, Kuan-Rau] Natl Yang Ming Univ, Sch Med, Fac Med, Taipei 112, Taiwan. [Su, Mao-Yuan M.; Tseng, Wen-Yih I.] Natl Taiwan Univ Hosp, Dept Med Imaging, Taipei, Taiwan. [Su, Mao-Yuan M.] Natl Yang Ming Univ, Inst Biomed Engn, Taipei 112, Taiwan. [Chiou, Kuan-Rau] Kaohsiung Vet Gen Hosp, Dept Med, Cardiol Sect, Kaohsiung 813, Taiwan. [Yang, Pinchen] Kaohsiung Med Univ, Coll Med, Dept Psychiat, Kaohsiung, Taiwan. [Yang, Pinchen] Kaohsiung Med Univ Hosp, Kaohsiung, Taiwan. [Pan, Huay-Ben] I Shou Univ, Coll Med Sci, Dept Radiat Technol, Kaohsiung, Taiwan. [Reese, Timothy G.; Wedeen, Van J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Martinos Ctr Biomed Imaging, Boston, MA USA. [Tseng, Wen-Yih I.] Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei, Taiwan. RP Wu, MT (reprint author), Kaohsiung Vet Gen Hosp, Dept Radiol, Sect Thorac & Circulat Imaging, 386 Ta Chung 1st Rd, Kaohsiung 813, Taiwan. EM wu.mingting@gmail.com RI Yang, Pan-Chyr /B-8808-2009; Huang, Yeou-Lih/C-9121-2009; OI SU, MAO-YUAN/0000-0002-6699-2298; Tseng, Wen-Yih Isaac/0000-0002-2314-6868 NR 30 TC 57 Z9 57 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2009 VL 2 IS 1 BP 32 EP 40 DI 10.1161/CIRCIMAGING.108.778902 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 446NT UT WOS:000266129000007 PM 19808562 ER PT J AU Nahrendorf, M Sosnovik, DE French, BA Swirski, FK Bengel, F Sadeghi, MM Lindner, JR Wu, JC Kraitchman, DL Fayad, ZA Sinusas, AJ AF Nahrendorf, Matthias Sosnovik, David E. French, Brent A. Swirski, Filip K. Bengel, Frank Sadeghi, Mehran M. Lindner, Jonathan R. Wu, Joseph C. Kraitchman, Dara L. Fayad, Zahi A. Sinusas, Albert J. TI Multimodality Cardiovascular Molecular Imaging, Part II SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Review DE molecular imaging; consensus; atherosclerosis; heart failure; myocardial infarction ID POSITRON-EMISSION-TOMOGRAPHY; MESENCHYMAL STEM-CELLS; REPORTER GENE-EXPRESSION; TARGETED CONTRAST AGENT; ATHEROSCLEROTIC PLAQUE INFLAMMATION; MATRIX-METALLOPROTEINASE ACTIVITY; CARDIAC TRANSPLANT REJECTION; ACUTE MYOCARDIAL-INFARCTION; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS C1 [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias; Sosnovik, David E.; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sosnovik, David E.] Harvard Univ, Sch Med, Boston, MA USA. [French, Brent A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. [Kraitchman, Dara L.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Sadeghi, Mehran M.] Yale Univ, Sch Med, Sect Cardiovasc Med, Cardiovasc Mol Imaging Lab, New Haven, CT USA. [Sadeghi, Mehran M.] VA Connecticut Healthcare Syst, New Haven, CT USA. [Lindner, Jonathan R.] Oregon Hlth & Sci Univ, Div Cardiovasc, Portland, OR 97201 USA. [Wu, Joseph C.] Stanford Univ, Sch Med, Dept Med Cardiol, Stanford, CA 94305 USA. [Wu, Joseph C.] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY USA. [Sinusas, Albert J.] Yale Univ, Sch Med, Dept Med & Diagnost Radiol, New Haven, CT USA. RP Nahrendorf, M (reprint author), MGH CMIR, 149 13th St, Charlestown, MA 02129 USA. EM mnahrendorf@mgh.harvard.edu; albert.sinusas@yale.edu FU NHLBI NIH HHS [R01 HL073223, R01 HL093038-01, R01 HL078650-04, K08 HL079984-05, R01 HL065662-04, R01 HL073223-04, R01 HL096576, R21 HL089027-02, R21 HL089029, R33 HL089029, R21/R33 HL089029, K08 HL079984, R01 HL085093, R01 HL095629, R21 HL089027, R33 HL089027, R01 HL065662, R21/R33 HL089027, R01 HL093038, R21 HL089029-02, R01 HL085093-02, R01 HL078650]; NIBIB NIH HHS [R01 EB007825] NR 146 TC 78 Z9 79 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2009 VL 2 IS 1 BP 56 EP 70 DI 10.1161/CIRCIMAGING.108.839092 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 446NT UT WOS:000266129000010 PM 19808565 ER PT J AU Parashar, S Rumsfeld, JS Reid, KJ Buchanan, D Dawood, N Khizer, S Lichtman, J Vaccarino, V AF Parashar, Susmita Rumsfeld, John S. Reid, Kimberly J. Buchanan, Donna Dawood, Nazeera Khizer, Saadia Lichtman, Judith Vaccarino, Viola CA PREMIER Registry Investigators TI Impact of Depression on Sex Differences in Outcome After Myocardial Infarction SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE sex; depression; myocardial infarction; women ID CORONARY-ARTERY-DISEASE; HEART-DISEASE; GENDER-DIFFERENCES; PATIENT OUTCOMES; MORTALITY; EVENTS; ANGINA; CARE; ASSOCIATION; SYMPTOMS AB Background-Women have an unexplained worse outcome after myocardial infarction (MI) compared with men in many studies. Depressive symptoms predict adverse post-MI outcomes and are more prevalent among women than men. We examined whether depressive symptoms contribute to women's worse outcomes after MI. Methods and Results-In a prospective multicenter study ( PREMIER), 2411 ( 807 women) MI patients were enrolled. Depressive symptoms were assessed with the Patient Health Questionnaire. Outcomes included 1-year rehospitalization, presence of angina using the Seattle Angina Questionnaire, and 2-year mortality. Multivariable analyses were used to evaluate the association between sex and these outcomes, adjusting for clinical characteristics. The depressive symptoms score was added to the models to evaluate whether it attenuated the association between sex and outcomes. Depressive symptoms were more prevalent in women compared with men (29% versus 18.8%, P < 0.001). After adjusting for demographic factors, comorbidities, and MI severity, women had a mildly higher risk of rehospitalization ( hazard ratio, 1.20; 95% CI, 1.04 to 1.40), angina ( odds ratio, 1.32; 95% CI, 1.00 to 1.75), and mortality ( hazard ratio, 1.27; 95% CI, 0.98 to 1.64). After adding depressive symptoms to the multivariable models, the relationship further declined toward the null, particularly for rehospitalization ( hazard ratio, 1.14; 95% CI, 0.98 to 1.34) and angina (odds ratio, 1.22; 95% CI, 0.91 to 1.63), whereas there was little change in the estimate for mortality ( hazard ratio, 1.24; 95% CI, 0.95 to 1.62). Depressive symptoms were significantly associated with each of the study outcomes with a similar magnitude of effect in both women and men. Conclusions-A higher prevalence of depressive symptoms in women modestly contributes to their higher rates of rehospitalization and angina compared with men but not mortality after MI. Our results support the recent recommendations of improving recognition of depressive symptoms after MI. ( Circ Cardiovasc Qual Outcomes. 2009;2:33-40.) C1 [Parashar, Susmita] Emory Univ, Sch Med, Dept Med, Div Cardiol,EPICORE, Atlanta, GA 30307 USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Reid, Kimberly J.; Buchanan, Donna] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Lichtman, Judith] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Parashar, S (reprint author), Emory Univ, Sch Med, Dept Med, Div Cardiol,EPICORE, 1256 Briarcliff Rd,Bldg A,Suite 1 N, Atlanta, GA 30307 USA. EM susmita.parashar@emory.edu FU Emory University General Clinical Research Center [NIH MO1-RR00039]; National Institutes of Health [K12RR17643, P50 HL077113]; Mentored Clinical Scientist Development [1K23RR023171]; [K24HL077506] FX Cardiovascular Therapeutics and Cardiovascular Outcomes funded the PREMIER data collection and analysis. This study was also supported by the Emory University General Clinical Research Center ( NIH MO1-RR00039) and National Institutes of Health grant K12RR17643. Dr Parashar is supported by Mentored Clinical Scientist Development Award 1K23RR023171. Dr Vaccarino is supported by grant K24HL077506. Ms Reid is supported through National Institutes of Health grant P50 HL077113. Ms Reid had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 31 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2009 VL 2 IS 1 BP 33 EP 40 DI 10.1161/CIRCOUTCOMES.108.818500 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575NL UT WOS:000276073800007 PM 20031810 ER PT J AU Miyauchi, K Takaya, N Hirose, T Ikeda, F Kawamori, R Ohishi, H Yoshida, K Yamamoto, M Arai, H Urabe, T Hattori, N Suzuki, M Maehara, T Sase, K Hatsukami, TS Yuan, C Daida, H AF Miyauchi, Katsumi Takaya, Norihide Hirose, Takahisa Ikeda, Fuki Kawamori, Ryuzo Ohishi, Hidenori Yoshida, Kensaku Yamamoto, Munetaka Arai, Hajime Urabe, Takao Hattori, Nobutaka Suzuki, Michimasa Maehara, Tadayuki Sase, Kazuhiro Hatsukami, Thomas S. Yuan, Chun Daida, Hiroyuki TI Rationale and Design of the Carotid Plaque in Human for All Evaluations With Aggressive Rosuvastatin Therapy (CHALLENGER Trial) - Evaluation by Magnetic Resonance Imaging SO CIRCULATION JOURNAL LA English DT Article DE Carotid intima-media thickness; Carotid plaque; High-resolution magnetic resonance imaging; Plaque stability; Rosuvastatin ID ACUTE CORONARY SYNDROME; INTRAVASCULAR ULTRASOUND; HEART-DISEASE; ATHEROSCLEROSIS; PREVENTION; PRAVASTATIN; REPRODUCIBILITY; STABILIZATION; ATHEROMA; JAPANESE AB Background Intensive lipid-lowering therapy with statins reduces levels of low-density lipoprotein (LDL)-C cholesterol (C) and improves plaque volume and composition in patients with cardiovascular disease. Furthermore. rosuvastatin ameliorated carotid stenosis in the ASTEROID study, and altered the composition of plaques in a predominantly Caucasian study population in the ORION study. However, it is not known whether statin therapy achieves similar quantitative improvement in carotid artery plaque in other ethnic groups. Methods and Results Fifty patients with hypercholesterolemia (LDL-C >= 120 mg/dl) and a maximum carotid intima-media thickness >= 1.8 mm will be enrolled and treated with rosuvastatin at a dose of 5 mg/day for 96 weeks. The primary endpoints will be the percent change of carotid plaque volume and the change in plaque composition after 96 weeks of treatment, as evaluated by magnetic resonance imaging. Conclusions The CHALLENGER study will provide a noninvasive assessment of the changes in carotid plaque volume and composition achieved by reduction of LDL levels in Japanese patients with carotid stenosis oil long-term rosuvastatin therapy. C1 [Daida, Hiroyuki] Juntendo Univ, Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Tokyo 1130033, Japan. [Hirose, Takahisa; Ikeda, Fuki; Kawamori, Ryuzo] Juntendo Univ, Sch Med, Dept Med, Tokyo 1130033, Japan. [Hirose, Takahisa; Ikeda, Fuki; Kawamori, Ryuzo] Juntendo Univ, Sch Med, Dept Endocrinol & Metab, Tokyo 1130033, Japan. [Ohishi, Hidenori; Yoshida, Kensaku; Yamamoto, Munetaka; Arai, Hajime] Juntendo Univ, Sch Med, Dept Neurosurg, Tokyo 1130033, Japan. [Urabe, Takao; Hattori, Nobutaka] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 1130033, Japan. [Suzuki, Michimasa; Maehara, Tadayuki] Juntendo Univ, Sch Med, Dept Radiol, Tokyo 1130033, Japan. [Sase, Kazuhiro] Juntendo Univ, Sch Med, Dept Clin Pharmacol, Tokyo 1130033, Japan. [Hatsukami, Thomas S.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Yuan, Chun] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Hatsukami, Thomas S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Daida, H (reprint author), Juntendo Univ, Sch Med, Dept Cardiovasc Med, Bunkyo Ku, 3-1-3 Hongo, Tokyo 1130033, Japan. EM daida@med.juntendo.ac.jp NR 27 TC 10 Z9 10 U1 0 U2 1 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD JAN PY 2009 VL 73 IS 1 BP 111 EP 115 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 388ZI UT WOS:000262058800019 PM 19057091 ER PT B AU Seely, EW Grinspoon, S AF Seely, Ellen W. Grinspoon, Steven BE Robertson, D Williams, GH TI Patient-Oriented Research: Clinical Pathophysiology and Clinical Therapeutics SO CLINICAL AND TRANSLATIONAL SCIENCE: PRINCIPLES OF HUMAN RESEARCH LA English DT Article; Book Chapter ID POSTMENOPAUSAL HORMONE-THERAPY; CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ESTROGEN THERAPY; GROWTH-HORMONE; RISK; WOMEN; ATHEROSCLEROSIS; LEPTIN C1 [Seely, Ellen W.] Brigham & Womens Hosp, Endocrinol Diabet & Hypertens Div, Boston, MA 02115 USA. [Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. RP Seely, EW (reprint author), Brigham & Womens Hosp, Endocrinol Diabet & Hypertens Div, 75 Francis St, Boston, MA 02115 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092019-1; 978-0-12-373639-0 PY 2009 BP 3 EP 12 DI 10.1016/B978-0-12-373639-0.00001-7 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHL23 UT WOS:000325772400003 ER PT B AU Erturk, SM Johnston, C Tempany-Afdhal, C Van den Abbeele, AD AF Erturk, Sukru Mehmet Johnston, Ciaran Tempany-Afdhal, Clare Van den Abbeele, Annick D. BE Robertson, D Williams, GH TI Imaging Tools in Human Research SO CLINICAL AND TRANSLATIONAL SCIENCE: PRINCIPLES OF HUMAN RESEARCH LA English DT Article; Book Chapter ID GASTROINTESTINAL STROMAL TUMORS; COMBINED PET/CT SCANNER; HUMAN BREAST-CANCER; CLINICAL ONCOLOGY; COMPUTED-TOMOGRAPHY; TREATMENT RESPONSE; IMATINIB MESYLATE; GENE-EXPRESSION; ENZYME-ACTIVITY; MR C1 [Erturk, Sukru Mehmet] Sisli Etfal Training & Res Hosp, Dept Radiol, Istanbul, Turkey. [Johnston, Ciaran; Tempany-Afdhal, Clare; Van den Abbeele, Annick D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Johnston, Ciaran] Dana Farber Canc Inst, Boston, MA 02115 USA. [Johnston, Ciaran; Tempany-Afdhal, Clare] Brigham & Womens Hosp, Boston, MA 02115 USA. [Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Van den Abbeele, Annick D.] Dana Farber Canc Inst, Ctr Bioimaging Oncol, Boston, MA 02115 USA. [Van den Abbeele, Annick D.] Dana Farber Harvard Canc Ctr, Tumor Imaging Metr Core, Boston, MA USA. RP Erturk, SM (reprint author), Sisli Etfal Training & Res Hosp, Dept Radiol, Istanbul, Turkey. NR 89 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092019-1; 978-0-12-373639-0 PY 2009 BP 87 EP 104 DI 10.1016/B978-0-12-373639-0.00006-6 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHL23 UT WOS:000325772400008 ER PT B AU Chueh, HC Murphy, SN AF Chueh, Henry C. Murphy, Shawn N. BE Robertson, D Williams, GH TI Information Technology SO CLINICAL AND TRANSLATIONAL SCIENCE: PRINCIPLES OF HUMAN RESEARCH LA English DT Article; Book Chapter ID DOUBLE DATA-ENTRY; DATA WAREHOUSE; DATABASE; DESIGN; HEALTH; TRIALS; RECRUITMENT; ISSUES; QUERY; CARE C1 [Chueh, Henry C.] Massachusetts Gen Hosp, Div Biomed Informat, Boston, MA 02114 USA. [Chueh, Henry C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chueh, Henry C.] MGH Clin Res Program, Boston, MA 02114 USA. [Murphy, Shawn N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chueh, HC (reprint author), Massachusetts Gen Hosp, Div Biomed Informat, Boston, MA 02114 USA. NR 34 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092019-1; 978-0-12-373639-0 PY 2009 BP 155 EP 167 DI 10.1016/B978-0-12-373639-0.00010-8 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHL23 UT WOS:000325772400012 ER PT B AU Koski, G AF Koski, Greg BE Robertson, D Williams, GH TI Ethical Issues in Translational Research and Clinical Investigation SO CLINICAL AND TRANSLATIONAL SCIENCE: PRINCIPLES OF HUMAN RESEARCH LA English DT Article; Book Chapter C1 [Koski, Greg] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Koski, Greg] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cardiac Anesthesia Grp, Boston, MA 02114 USA. [Koski, Greg] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Koski, G (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092019-1; 978-0-12-373639-0 PY 2009 BP 415 EP 428 DI 10.1016/B978-0-12-373639-0.00028-5 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHL23 UT WOS:000325772400030 ER PT J AU Kesari, S Schiff, D Drappatz, J LaFrankie, D Doherty, L Macklin, EA Muzikansky, A Santagata, S Ligon, KL Norden, AD Ciampa, A Bradshaw, J Levy, B Radakovic, G Ramakrishna, N Black, PM Wen, PY AF Kesari, Santosh Schiff, David Drappatz, Jan LaFrankie, Debra Doherty, Lisa Macklin, Eric A. Muzikansky, Alona Santagata, Sandro Ligon, Keith L. Norden, Andrew D. Ciampa, Abigail Bradshaw, Joanna Levy, Brenda Radakovic, Gospova Ramakrishna, Naren Black, Peter M. Wen, Patrick Y. TI Phase II Study of Protracted Daily Temozolomide for Low-Grade Gliomas in Adults SO CLINICAL CANCER RESEARCH LA English DT Article ID LOW-DOSE TEMOZOLOMIDE; RANDOMIZED-TRIAL; EUROPEAN-ORGANIZATION; VINCRISTINE CHEMOTHERAPY; METRONOMIC CHEMOTHERAPY; DNA METHYLTRANSFERASE; PROGNOSTIC-FACTORS; RADIATION-THERAPY; MALIGNANT GLIOMAS; PCV CHEMOTHERAPY AB Purpose: Resistance to temozolomide chemotherapy is partly mediated by O(6)-methylguanine-DNA methlytransferase (MGMT). Protracted treatment with temozolomide potentially overcomes MGMT resistance and improves outcome. We conducted a phase 11 study of protracted daily temozolomide in adults with low-grade gliomas. Experimental Design: Patients with newly diagnosed oligodendroglioma or oligoastrocytoma with a MIB-1 index of > 5% or recurrent low-grade gliomas received temozolomide (75 mg/m(2)/day in 11-week cycles of 7 weeks on/4 weeks off). Treatment continued for a total of six cycles or until tumor progression or unacceptable toxicity. Primary end point was best overall response rate; secondary end points were progression-free survival, overall survival, and toxicity. We correlated response with MGMT promoter methylation and chromosome 1p/19q deletion status. Results: Forty-four patients were treated (14 female, 30 male) with a median follow-up of 39.4 months. Median age was 43 years (range, 20-68 years) and median Karnofsky performance status was 90 (range, 70-100). The regimen was well tolerated. No patients had a complete response (0%), 9 had partial response (20%), 33 had stable disease (75%), and 2 had progressive disease (5%). A total of 21 patients eventually progressed with an overall median progression-free survival of 38 months. Patients with methylated MGMT promoter had a longer overall survival (P = 0.008). Deletion of either 1p or 19q chromosomes also predicted longer overall survival (hazard ratio, 0.17; 95% confidence interval, 0.03-0.93; log-rank P = 0.02). Conclusions: A protracted course of daily temozolomide is a well-tolerated regimen and seems to produce effective tumor control. This compares favorably with historical data on the standard 5-day temozolomide regimen. C1 [Kesari, Santosh; Drappatz, Jan; LaFrankie, Debra; Doherty, Lisa; Norden, Andrew D.; Ciampa, Abigail; Bradshaw, Joanna; Levy, Brenda; Ramakrishna, Naren; Black, Peter M.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Kesari, Santosh; Drappatz, Jan; Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Santagata, Sandro; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramakrishna, Naren] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Black, Peter M.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Kesari, Santosh; Drappatz, Jan; Macklin, Eric A.; Muzikansky, Alona; Santagata, Sandro; Ligon, Keith L.; Norden, Andrew D.; Ramakrishna, Naren; Black, Peter M.; Wen, Patrick Y.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Macklin, Eric A.; Muzikansky, Alona] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Schiff, David; Radakovic, Gospova] Univ Virginia, Neurooncol Ctr, Charlottesville, VA USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 44 Binney St,SW430D, Boston, MA 02115 USA. EM pwen@partners.org RI Macklin, Eric/E-2955-2013; Kesari, Santosh/E-8461-2013 OI Macklin, Eric/0000-0003-1618-3502; FU Schering-Plough Corporation FX Grant support: Schering-Plough Corporation. NR 38 TC 72 Z9 75 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2009 VL 15 IS 1 BP 330 EP 337 DI 10.1158/1078-0432.CCR-08-0888 PG 8 WC Oncology SC Oncology GA 391JO UT WOS:000262229800038 PM 19118062 ER PT J AU Kulke, MH Hornick, JL Frauenhoffer, C Hooshmand, S Ryan, DP Enzinger, PC Meyerhardt, JA Clark, JW Stuart, K Fuchs, CS Redston, MS AF Kulke, Matthew H. Hornick, Jason L. Frauenhoffer, Christine Hooshmand, Susanne Ryan, David P. Enzinger, Peter C. Meyerhardt, Jeffrey A. Clark, Jeffrey W. Stuart, Keith Fuchs, Charles S. Redston, Mark S. TI O-6-Methylguanine DNA Methyltransferase Deficiency and Response to Temozolomide-Based Therapy in Patients with Neuroendocrine Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; PHASE-II TRIAL; ISLET-CELL-CARCINOMA; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; PROMOTER HYPERMETHYLATION; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE; METHYLATION STATUS; MALIGNANT GLIOMA; MGMT; DACARBAZINE AB Purpose: Recent studies suggest that temozolomide has activity in neuroendocrine tumors. Low levels of the DNA repair enzyme, O-6-methylguanine DNA methyltransferase (MGMT), are associated with sensitivity to temozolomide in other tumor types. We evaluated the prevalence of MGMT deficiency in neuroendocrine tumors and correlated MGMT deficiency with treatment response to temozolomide-based regimens. Experimental Design: The prevalence of MGMT deficiency, measured by immunohistochemistry, was assessed in 97 archival neuroendocrine tumor specimens. Rates of treatment response and survival were next evaluated in a cohort of 101 consecutive neuroendocrine tumor patients who had received treatment with a temozolomide-based regimen at one of three institutions. MGMT expression was directly correlated with treatment response in 21 patients who had available tumor tissue and response data. Results: In archival specimens, MGMT deficiency was observed in 19 of 37 (51%) pancreatic neuroendocrine tumors and 0 of 60 (0%) carcinoid tumors (P < 0.0001). In the clinical cohort, 18 of 53 (34%) patients with pancreatic neuroendocrine tumors but only 1 of 44 (2%) patients with carcinoid tumors (P < 0.001) experienced a partial or complete response to temozolomide-based therapy. Among 21 patients with evaluable tumor tissue who had also received treatment with temozolomide, 4 of 5 patients with MGMT-deficient tumors (all pancreatic neuroendocrine tumors) and 0 of 16 patients with tumors showing intact MGMT expression responded to treatment (P = 0.001). Conclusions: MGMT deficiency, measured by immunohistochemistry, is more common in pancreatic neuroendocrine tumors than in carcinoid tumors as is treatment response to temozolomide-based therapy. Absence of MGMT may explain the sensitivity of some pancreatic neuroendocrine tumors to treatment. C1 [Kulke, Matthew H.; Frauenhoffer, Christine; Hooshmand, Susanne; Enzinger, Peter C.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hornick, Jason L.; Redston, Mark S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ryan, David P.; Clark, Jeffrey W.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Stuart, Keith] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU National Cancer Institute; Dana-Farber/Harvard Cancer Center SPORE in Gastrointestinal Cancer [P50 CA127003] FX Grant support: National Cancer Institute grants CA093401 (M.H. Kulke) and P50 CA127003 (Dana-Farber/Harvard Cancer Center SPORE in Gastrointestinal Cancer). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this NR 45 TC 164 Z9 168 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 JAN 1 PY 2009 VL 15 IS 1 BP 338 EP 345 DI 10.1158/1078-0432.CCR-08-1476 PG 8 WC Oncology SC Oncology GA 391JO UT WOS:000262229800039 PM 19118063 ER PT J AU Treon, SP Soumerai, JD Branagan, AR Hunter, ZR Patterson, CJ Loakimidis, L Chu, L Musto, P Baron, AD Nunnink, JC Kash, JJ Terjanian, TO Hyman, PM Nawfel, EL Sharon, DJ Munshi, NC Anderson, KC AF Treon, Steven P. Soumerai, Jacob D. Branagan, Andrew R. Hunter, Zachary R. Patterson, Christopher J. Loakimidis, Leukothea Chu, Luis Musto, Paul Baron, Ari D. Nunnink, Johannes C. Kash, Joseph J. Terjanian, Terenig O. Hyman, Paul M. Nawfel, Elena L. Sharon, David J. Munshi, Nikhil C. Anderson, Kenneth C. TI Lenalidomide and Rituximab in Waidenstrom's Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; NON-HODGKINS-LYMPHOMA; WALDENSTROMS MACROGLOBULINEMIA; CLINICAL-RESPONSE; THERAPY; CLASSIFICATION; THALIDOMIDE; EXPRESSION; UPDATE AB Purpose: Thalidomide and its more potent immunomodulatory derivative lenalidomide enhance rituximab-mediated antibody-dependent cell-mediated cytotoxicity. We therefore evaluated lenalidomide and rituximab in symptomatic Waldenstrom's macrogloblinemia (WM) patients naive to either agent. Experimental Design: Intended therapy consisted of 48 weeks of lenalidomide (25 mg/d for 3 weeks and then 1 week off) along with rituximab (375 mg/m(2)/wk) dosed on weeks 2 to 5 and 13 to 16. Sixteen patients were enrolled, 12 of whom were previously untreated. Results: Unexpectedly, we observed an acute decrease in hematocrit in 13 of 16 patients (median hematocrit decrease, 4.8%), which was attributable to lenalidomide patients and which led to cessation of further enrollment on this study. Lenalidomide-related anemia was observed even at doses as low as 5 mg/d and occurred in the absence of hemolysis or other cytopenias. The overall response and major response (< 50% decrease in serum IgM) rates were 50% and 25%, respectively, on an intent-to-treat basis. With a median follow-up of 31.3 months, 4 of 8 responding patients have progressed with a median time to progression of 18.9 months. Conclusion: Lenalidomide produces unexpected but clinically significant acute anemia in patients with WM. In comparison with our previous study with thalidomide and rituximab in an analogous patient population, the responses achieved in WM patients with lenalidomide and rituximab appear less favorable. C1 [Treon, Steven P.; Soumerai, Jacob D.; Branagan, Andrew R.; Hunter, Zachary R.; Patterson, Christopher J.; Loakimidis, Leukothea] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Treon, Steven P.; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Boston, MA USA. [Chu, Luis] Florida Canc Specialists, Sarasota, FL USA. [Musto, Paul] Commonwealth Hematol Oncol, Quincy, MA USA. [Baron, Ari D.] Pacific Hematol Oncol Associates, San Francisco, CA USA. [Nunnink, Johannes C.] Univ Vermont, Ctr Canc, Burlington, VT USA. [Kash, Joseph J.] Edward Hosp & Hlth Serv, Ctr Canc, Naperville, IL USA. [Terjanian, Terenig O.] Sanford R Nalitt Inst Canc & Related Blood Dis, Staten Isl, NY USA. [Hyman, Paul M.] Hematol Oncol Associates Western Suffolk PC, Bay Shore, NY USA. [Nawfel, Elena L.] Harold Alfond Ctr Canc Care, Augusta, ME USA. [Sharon, David J.] Monmouth Med Ctr, Long Beach, CA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,44 Binney St, Boston, MA 02115 USA. EM steven-treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU Waldensubm's at the Dana-Farber Cancer Institute; NIH Development Award [K23CA087977-03] FX Bing Fund for Waidenstrom's macroglobulinemia, Research Fund for Waldensubm's at the Dana-Farber Cancer Institute, and NIH Development Award K23CA087977-03 (S.P.Treon). NR 22 TC 53 Z9 53 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 JAN 1 PY 2009 VL 15 IS 1 BP 355 EP 360 DI 10.1158/1078-0432.CCR-08-0862 PG 6 WC Oncology SC Oncology GA 391JO UT WOS:000262229800041 PM 19118065 ER PT J AU Zhu, AX Ready, N Clark, JW Safran, H Amato, A Salem, N Pace, S He, XY Zvereva, N Lynch, TJ Ryan, DP Supko, AG AF Zhu, Andrew X. Ready, Neal Clark, Jeffrey W. Safran, Howard Amato, Antonino Salem, Nadia Pace, Silvia He, Xiaoying Zvereva, Nela Lynch, Thomas J. Ryan, David P. Supko, Andjeffrey G. TI Phase I and Pharmacokinetic Study of Gimatecan Given Orally Once a Week for 3 of 4 Weeks in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC COLORECTAL-CANCER; POTENT ANTITUMOR-ACTIVITY; CAMPTOTHECIN GIMATECAN; FLUOROURACIL FAILURE; RANDOMIZED-TRIAL; IRINOTECAN; PLASMA; ST1481; DRUGS; DERIVATIVES AB Purpose: A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of gimatecan, a lipophilic camptothecin analogue, administered orally once a week for 3 weeks. Experimental Design: Adult patients with advanced solid tumors with good performance status and adequate hematologic, hepatic, and renal function were eligible for the study. The plasma pharmacokinetics of the drug was characterized during the initial 28-day cycle. Results: A total of 33 patients were evaluated at 7 dose levels ranging from 0.27 to 3.20 mg/m(2)/wk. Anemia, fatigue, neutropenia, nausea, and vomiting were the principal toxicities. DLTs experienced by 3 of 7 patients in dose level 7 (3.20 mg/m(2)) were grade 2 hyperbilirubinemia and grade 3 to 4 fatigue. DLT (anorexia and nausea) occurred in only 1 of 11 patients evaluated at the MTD of 2.40 mg/m(2). There were no objective responses, although disease stabilization was observed in 4 patients. Gimatecan has a very long apparent biological half-life (mean +/- SD, 77 +/- 37 h) and exists in plasma almost entirely as the pharmacologically active intact lactone form. At the MTD, mean peak concentrations of the drug in plasma ranged from 67 to 82 ng/mL for the 3 weekly doses and the mean concentration 7 days after dosing was 15 +/- 18 ng/mL. Conclusions: Administration of gimatecan orally once a week at doses that are well tolerated provides continuous exposure to potentially effective plasma concentrations of the biologically active form of the drug. This regimen deserves further evaluation to define its antitumor activity in specific tumor types either alone or in combination with other agents. C1 [Zhu, Andrew X.; Clark, Jeffrey W.; He, Xiaoying; Zvereva, Nela; Lynch, Thomas J.; Ryan, David P.; Supko, Andjeffrey G.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ready, Neal; Safran, Howard] Rhode Isl Hosp, Brown Med Sch, Providence, RI USA. [Amato, Antonino; Salem, Nadia] Sigma Tau Res Inc, Gaithersburg, MD USA. [Pace, Silvia] Sigma Tau Pharmaceut Co, Pomezia, Italy. RP Zhu, AX (reprint author), Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Massachusetts Gen Hosp, 55 Fruit St,LH-POB 232, Boston, MA 02114 USA. EM azhu@partners.org FU Sigma-Tau Research FX Grant support: Sigma-Tau Research. NR 35 TC 11 Z9 12 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 JAN 1 PY 2009 VL 15 IS 1 BP 374 EP 381 DI 10.1158/1078-0432.CCR-08-1024 PG 8 WC Oncology SC Oncology GA 391JO UT WOS:000262229800044 PM 19118068 ER PT J AU Morrow, DA Antman, EM AF Morrow, David A. Antman, Elliott M. TI Evaluation of High-Sensitivity Assays for Cardiac Troponin SO CLINICAL CHEMISTRY LA English DT Editorial Material ID MEDICINE PRACTICE GUIDELINES; ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; CLINICAL BIOCHEMISTRY; NATIONAL ACADEMY; COMMITTEE; MARKERS C1 [Morrow, David A.; Antman, Elliott M.] Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 14 TC 63 Z9 65 U1 0 U2 5 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 JAN PY 2009 VL 55 IS 1 BP 5 EP 8 DI 10.1373/clinchem.2008.117218 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 392LJ UT WOS:000262303900002 PM 19028812 ER PT J AU Burnett-Bowie, SAM Roupenian, KC Dere, ME Lee, H Leder, BZ AF Burnett-Bowie, Sherri-Ann M. Roupenian, Kristen C. Dere, Melissa E. Lee, Hang Leder, Benjamin Z. TI Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial SO CLINICAL ENDOCRINOLOGY LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; ESTROGEN PLUS PROGESTIN; LOW SERUM TESTOSTERONE; POSTMENOPAUSAL WOMEN; ELDERLY-MEN; REPLACEMENT THERAPY; BODY-COMPOSITION; PLASMA-LIPOPROTEINS; LUTEINIZING-HORMONE; ANDROGEN DEFICIENCY AB To assess the effects of sustained aromatase inhibition in older hypogonadal men. In a 1-year randomized, double-blind, placebo-controlled trial, 88 men, aged 60 years and older with testosterone levels between 5.2 and 10.4 nmol/l on a single measure or between 10.4 and 12.1 nmol/l on two consecutive measures, and with symptoms of hypogonadism were recruited. Subjects received either anastrozole 1 mg daily or placebo. Changes in gonadal steroid hormone levels, body composition [by computerized tomography (CT) and dual X-ray absorptiometry (DXA)], strength, prostate specific antigen (PSA), symptoms of benign prostatic hypertrophy (BPH), haematocrit and lipid levels were assessed. Testosterone levels increased from 11.2 +/- 3.3 nmol/l at baseline to 18.2 +/- 4.8 nmol/l at month 3 (P < 0.0001 vs. placebo) while bioavailable testosterone levels increased from 2.7 +/- 0.8 nmol/l at baseline to 5.4 +/- 1.7 nmol/l at month 3 (P < 0.0001 vs. placebo). Testosterone and biotestosterone levels peaked at month 3 and then declined by month 12 (though they remained significantly higher than baseline and greater than placebo). E-2 levels decreased from 55.8 +/- 15.4 pmol/l at baseline to 42.2 +/- 13.6 pmol/l at month 3 and then remained stable (P < 0.0001). Body composition and strength did not change, nor did PSA, BPH symptoms, haematocrit or lipid levels. Anastrozole administration normalized androgen production in older hypogonadal men and decreased E-2 production modestly. These alterations did not improve body composition or strength. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Burnett-Bowie, SAM (reprint author), 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM sburnett-bowie@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU National Institute of Health [K23-RR-161310, R01-AG-025099-03, M01-RR-01066]; AstraZeneca Pharmaceuticals FX The authors are grateful to the staff of the MGH Mallinckrodt GCRC for the implementation of the study protocol and to Dr Joel Finkelstein for his helpful suggestions. Funding: National Institute of Health grants K23-RR-161310 (to BZL), R01-AG-025099-03 (to BZL), M01-RR-01066 (to the Mallinckrodt GCRC) and AstraZeneca Pharmaceuticals. NR 46 TC 22 Z9 23 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2009 VL 70 IS 1 BP 116 EP 123 DI 10.1111/j.1365-2265.2008.03327.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 389OW UT WOS:000262105400018 PM 18616708 ER PT J AU Cronin, CG Moore, M Blake, MA AF Cronin, Carmel G. Moore, Michael Blake, Michael A. TI Positron Emission Tomography/Computerized Tomography for the Gastroenterologist and Hepatologist SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; RECURRENT COLORECTAL-CANCER; IN-LINE PET/CT; ESOPHAGEAL CANCER; F-18-FDG PET; COMPUTED-TOMOGRAPHY; GALLBLADDER CANCER; PANCREATIC-CANCER; GASTRIC-CANCER; HEPATOCELLULAR-CARCINOMA C1 [Cronin, Carmel G.; Moore, Michael; Blake, Michael A.] Massachusetts Gen Hosp, Dept Abdominal & Intervent Radiol, Boston, MA 02114 USA. RP Cronin, CG (reprint author), Massachusetts Gen Hosp, Dept Abdominal & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM carmelcronin2000@hotmail.com NR 52 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2009 VL 7 IS 1 BP 20 EP 26 DI 10.1016/j.cgh.2008.10.033 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 399TK UT WOS:000262822000007 PM 19041954 ER PT J AU Jongmans, MCJ van Ravenswaaij-Arts, CMA Pitteloud, N Ogata, T Sato, N Claahsen-van der Grinten, HL van der Donk, K Seminara, S Bergman, JEH Brunner, HG Crowley, WF Hoefsloot, LH AF Jongmans, M. C. J. van Ravenswaaij-Arts, C. M. A. Pitteloud, N. Ogata, T. Sato, N. Claahsen-van der Grinten, H. L. van der Donk, K. Seminara, S. Bergman, J. E. H. Brunner, H. G. Crowley, W. F., Jr. Hoefsloot, L. H. TI CHD7 mutations in patients initially diagnosed with Kallmann syndrome - the clinical overlap with CHARGE syndrome SO CLINICAL GENETICS LA English DT Article DE anosmia; CHARGE syndrome; CHD7 gene; hypogonadotropic hypogonadism; Kallmann syndrome ID HYPOGONADOTROPIC HYPOGONADISM; GENE; PHENOTYPE; SPECTRUM; MOLECULES; ADHESION; FGFR1 AB Kallmann syndrome (KS) is the combination of hypogonadotropic hypogonadism and anosmia or hyposmia, two features that are also frequently present in CHARGE syndrome. CHARGE syndrome is caused by mutations in the CHD7 gene. We performed analysis of CHD7 in 36 patients with KS and 20 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) in whom mutations in KAL1, FGFR1, PROK2 and PROKR2 genes were excluded. Three of 56 KS/nIHH patients had de novo mutations in CHD7. In retrospect, these three CHD7-positive patients showed additional features that are seen in CHARGE syndrome. CHD7 mutations can be present in KS patients who have additional features that are part of the CHARGE syndrome phenotype. We did not find mutations in patients with isolated KS. These findings imply that patients diagnosed with hypogonadotropic hypogonadism and anosmia should be screened for clinical features consistent with CHARGE syndrome. If such features are present, particularly deafness, dysmorphic ears and/or hypoplasia or aplasia of the semicircular canals, CHD7 sequencing is recommended. C1 [Jongmans, M. C. J.; van der Donk, K.; Brunner, H. G.; Hoefsloot, L. H.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [van Ravenswaaij-Arts, C. M. A.; Bergman, J. E. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 AB Groningen, Netherlands. [Pitteloud, N.; Seminara, S.; Crowley, W. F., Jr.] Harvard Univ, Reprod Endocrine Sci Ctr, Boston, MA 02115 USA. [Pitteloud, N.; Seminara, S.; Crowley, W. F., Jr.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Ogata, T.; Sato, N.] Natl Res Inst Child Hlth & Dev, Dept Endocrinol & Metab, Tokyo, Japan. [Claahsen-van der Grinten, H. L.] Radboud Univ Nijmegen, Med Ctr, Dept Pediat Endocrinol, NL-6525 ED Nijmegen, Netherlands. RP Jongmans, MCJ (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM m.jongmans@antrg.umcn.nl RI Brunner, Han/C-9928-2013; PITTELOUD, Nelly/K-2709-2014; Claahsen-van der Grinten, H.L./L-4247-2015; OI Bergman, Jorieke/0000-0002-3929-3619 FU NICHD Center of Excellence Program; Netherlands Organisation for Health Research FX Drs Pitteloud, Seminara and Crowley were supported by the NICHD Center of Excellence Program, Drs Ogata and Sato were supported by a Grant-in-Aid for Scientific Research on Priority areas, and Dr. Bergman was supported by a grant from the Netherlands Organisation for Health Research. NR 21 TC 80 Z9 86 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 2009 VL 75 IS 1 BP 65 EP 71 DI 10.1111/j.1399-0004.2008.01107.x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 389XP UT WOS:000262129200011 PM 19021638 ER PT J AU Morris, MJ Basch, EM Wilding, G Hussain, M Carducci, MA Higano, C Kantoff, P Oh, WK Small, EJ George, D Mathew, P Beer, TM Slovin, SF Ryan, C Logothetis, C Scher, HI AF Morris, Michael J. Basch, Ethan M. Wilding, George Hussain, Maha Carducci, Michael A. Higano, Celestia Kantoff, Philip Oh, William K. Small, Eric J. George, Daniel Mathew, Paul Beer, Tomaz M. Slovin, Susan F. Ryan, Charles Logothetis, Christopher Scher, Howard I. TI Department of Defense Prostate Cancer Clinical Trials Consortium: A New Instrument for Prostate Cancer Clinical Research SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Clinical consortium; Collaborative; Infrastructure; Phase I/II trial ID END-POINTS; WORKING GROUP; RECOMMENDATIONS; ELIGIBILITY AB Background: In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). Patients and Methods: The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >= 1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. Results: The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. Conclusion: The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals. C1 [Morris, Michael J.; Basch, Ethan M.; Slovin, Susan F.; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10065 USA. [Morris, Michael J.; Basch, Ethan M.; Slovin, Susan F.; Scher, Howard I.] Cornell Univ, Dept Med, Joan & Sanford E Weill Coll Med, New York, NY 10021 USA. [Wilding, George] Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI USA. [Hussain, Maha] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hussain, Maha] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Carducci, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Higano, Celestia] Univ Washington, Dept Med, Seattle, WA USA. [Higano, Celestia] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Kantoff, Philip; Oh, William K.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Kantoff, Philip; Oh, William K.] Harvard Univ, Sch Med, Boston, MA USA. [Small, Eric J.; Ryan, Charles] Univ Calif San Francisco, UCSF Canc Ctr, San Francisco, CA 94143 USA. [George, Daniel] Duke Univ, Dept Surg, Duke Comprehens Canc Ctr, Div Urol, Durham, NC USA. [Mathew, Paul; Logothetis, Christopher] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Beer, Tomaz M.] Oregon Hlth & Sci Univ, OHSU Canc Inst, Portland, OR 97201 USA. RP Scher, HI (reprint author), Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10065 USA. EM scherh@mskcc.org RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Morris, Michael J./0000-0002-9454-0096 FU US Department of Defense Prostate Cancer Research Program; Prostate Cancer Foundation FX This study is Supported by the US Department of Defense Prostate Cancer Research Program and the Prostate Cancer Foundation. The authors wish to thank Mary Warren, MSW; Jake Vinson, MHA; Moshe Kelsen; Elizabeth Brand; and Hope J. Lafferty, MA, ELS, of the PCCTC for their assistance in preparing this manuscript. NR 14 TC 13 Z9 13 U1 0 U2 1 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 JAN PY 2009 VL 7 IS 1 BP 51 EP 57 DI 10.3816/CGC.2009.n.009 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 406UC UT WOS:000263319400009 PM 19213669 ER PT J AU Allen, RS Phillips, LL Pekmezi, D Crowther, MR Prentice-Dunn, S AF Allen, Rebecca S. Phillips, Laura L. Pekmezi, Dorothy Crowther, Martha R. Prentice-Dunn, Steven TI Living Well with Living Wills: Application of Protection Motivation Theory to Living Wills Among Older Caucasian and African American Adults SO CLINICAL GERONTOLOGIST LA English DT Article DE living wills; race/ethnicity and health; protection motivation theory; preventive health ID LIFE-SUSTAINING TREATMENTS; ADVANCE DIRECTIVES; DECISION-MAKING; INDIVIDUAL-DIFFERENCES; FAMILY CAREGIVERS; END; PREFERENCES; HEALTH; INFORMATION; RESPONSES AB Using protection motivation theory, we examined racial differences in intent to complete a living will, rational problem solving (e.g., information seeking), and maladaptive coping responses (i.e., wishful thinking) to a health crisis. Sixty healthy, older adults without living wills responded to written vignettes, including information about living wills as an effective coping mechanism to avoid a health crisis. Use of adaptive coping responses predicted intent to execute a living will. A significant race-by-threat interaction predicted use of rational problem solving, with Caucasians more likely to seek information in response to perceived threat in comparison with African Americans. A significant race-by-adaptive-coping interaction predicted maladaptive coping, indicating that Caucasians were more variable in their maladaptive responses. The effectiveness of health care messages regarding living wills for older adults may be enhanced by focusing on racial differences in response to perceived health threat and perceived adaptive coping information. C1 [Allen, Rebecca S.; Crowther, Martha R.; Prentice-Dunn, Steven] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. [Allen, Rebecca S.; Crowther, Martha R.] Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. [Phillips, Laura L.] Houston Vet Affairs Med Ctr, Houston, TX USA. [Pekmezi, Dorothy] Miriam Hosp, Providence, RI 02906 USA. [Pekmezi, Dorothy] Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI USA. RP Allen, RS (reprint author), Univ Alabama, Dept Psychol, Box 870348, Tuscaloosa, AL 35487 USA. EM rsallen@bama.ua.edu OI Allen, Rebecca Sue/0000-0002-2563-4996 FU National Institute on Aging [K01AG00943]; Department of Psychology at The University of Alabama FX Portions of this article were presented at the 56th annual scientific meeting of the Gerontological Society of America, San Diego, CA, November 2003. Funding from the National Institute on Aging (K01AG00943) to Rebecca S. Allen partially supported data collection for this project and preparation of this manuscript. Additionally, funding for data collection was provided by the Department of Psychology at The University of Alabama as part of Dorothy Pekmezi's undergraduate honors thesis. NR 26 TC 6 Z9 6 U1 2 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-7115 J9 CLIN GERONTOLOGIST JI Clin. Gerontol. PY 2009 VL 32 IS 1 BP 44 EP 59 DI 10.1080/07317110802474643 PG 16 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 675UP UT WOS:000283864400004 PM 19337566 ER PT J AU Albacker, L Karisola, P Umetsu, S Akbari, O Freeman, G Umetsu, D DeKruyff, R AF Albacker, Lee Karisola, Piia Umetsu, Sarah Akbari, Omid Freeman, Gordon Umetsu, Dale DeKruyff, Rosemarie TI TIM-4 Negatively Regulates Immune Responses by Reducing Antigen Specific T Cell Numbers SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Albacker, Lee; Karisola, Piia; Akbari, Omid; Umetsu, Dale; DeKruyff, Rosemarie] Childrens Hosp, Boston, MA 02115 USA. [Albacker, Lee; Karisola, Piia; Akbari, Omid; Freeman, Gordon; Umetsu, Dale; DeKruyff, Rosemarie] Harvard Univ, Sch Med, Boston, MA USA. [Umetsu, Sarah] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Freeman, Gordon] Dana Farber Canc Inst, Boston, MA 02115 USA. 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S53 EP S53 DI 10.1016/j.clim.2009.03.150 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300144 ER PT J AU Albacker, L Karisola, P Umetsu, S Akbari, O Freeman, G Umetsu, D DeKruyff, R AF Albacker, Lee Karisola, Piia Umetsu, Sarah Akbari, Omid Freeman, Gordon Umetsu, Dale DeKruyff, Rosemarie TI TIM-4 Negatively Regulates Immune Responses by Reducing Antigen Specific T Cell Numbers SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Albacker, Lee; Karisola, Piia; Akbari, Omid; Freeman, Gordon; Umetsu, Dale; DeKruyff, Rosemarie] Harvard Univ, Sch Med, Boston, MA USA. [Albacker, Lee; Karisola, Piia; Akbari, Omid; Umetsu, Dale; DeKruyff, Rosemarie] Childrens Hosp, Boston, MA 02115 USA. [Umetsu, Sarah] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Freeman, Gordon] Dana Farber Canc Inst, Boston, MA 02115 USA. 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S36 EP S36 DI 10.1016/j.clim.2009.03.101 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300096 ER PT J AU Andreola, G Chittenden, M Shaffer, J Cosimi, B Kawai, T Cotter, P Dey, B Tolkoff-Rubin, N Preffer, F Saidman, S Kottleman, K Spitzer, T Sachs, D Sykes, M AF Andreola, Giovanna Chittenden, Meredith Shaffer, Juanita Cosimi, Benedict Kawai, Tatsuo Cotter, Pete Dey, Bimalangshu Tolkoff-Rubin, Nina Preffer, Frederic Saidman, Susan Kottleman, Kristin Spitzer, Thomas Sachs, David Sykes, Megan TI Mechanisms of Donor-Specific Unresponsiveness Following Loss of Chimerism in Recipients of Haploidentical Combined Bone Marrow/Kidney Transplantation SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Andreola, Giovanna; Chittenden, Meredith; Shaffer, Juanita; Cosimi, Benedict; Kawai, Tatsuo; Cotter, Pete; Dey, Bimalangshu; Tolkoff-Rubin, Nina; Preffer, Frederic; Saidman, Susan; Kottleman, Kristin; Spitzer, Thomas; Sachs, David; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S60 EP S60 DI 10.1016/j.clim.2009.03.173 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300167 ER PT J AU Drouin, E Seward, R Costello, C Steere, A AF Drouin, Elise Seward, Robert Costello, Catherine Steere, Allen TI HLA-DRB1-Presented Peptides in Inflamed Synovium from Patients with Rheumatoid Arthritis or Anti biotic-Refractory Lyme Arthritis SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Drouin, Elise; Seward, Robert; Steere, Allen] Massachusetts Gen Hosp, Charlestown, MA USA. [Drouin, Elise; Seward, Robert; Steere, Allen] Harvard Univ, Sch Med, Charlestown, MA USA. [Costello, Catherine] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S152 EP S152 DI 10.1016/j.clim.2009.03.448 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300440 ER PT J AU Fingeroth, J AF Fingeroth, Joyce TI Epstein-Barr Virus Replicative Cycle Proteins in the Pathogenesis of Human Disease SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Fingeroth, Joyce] BIDMC, Boston, MA USA. [Fingeroth, Joyce] Harvard Univ, Sch Med, Boston, MA 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S79 EP S79 DI 10.1016/j.clim.2009.03.231 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300224 ER PT J AU Francisco, L Salinas, V Brown, K Vanguri, V Freeman, G Kuchroo, V Sharpe, A AF Francisco, Loise Salinas, Victor Brown, Keturah Vanguri, Vijay Freeman, Gordon Kuchroo, Vijay Sharpe, Arlene TI PD-L1 Regulates the Development, Maintenance and Function of Induced-regulatory T Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Francisco, Loise; Salinas, Victor; Brown, Keturah; Vanguri, Vijay; Kuchroo, Vijay; Sharpe, Arlene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Freeman, Gordon] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S45 EP S45 DI 10.1016/j.clim.2009.03.126 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300120 ER PT J AU Francisco, L Salinas, V Brown, K Vanguri, V Freeman, G Kuchroo, V Sharpe, A AF Francisco, Loise Salinas, Victor Brown, Keturah Vanguri, Vijay Freeman, Gordon Kuchroo, Vijay Sharpe, Arlene TI PD-L1 Regulates the Development, Maintenance and Function of Induced-regulatory T Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Francisco, Loise; Salinas, Victor; Brown, Keturah; Vanguri, Vijay; Kuchroo, Vijay; Sharpe, Arlene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Freeman, Gordon] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S41 EP S41 DI 10.1016/j.clim.2009.03.115 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300110 ER PT J AU Hazen, M McArdel, S Ercan, A Ortiz-Lopez, A Benoist, C Mathis, D Lee, D AF Hazen, Melissa McArdel, Shannon Ercan, Alton Ortiz-Lopez, Adriana Benoist, Christophe Mathis, Diane Lee, David TI Modulation of Autoantibody Glycosylation during Arthritis in the K/BxN Mouse SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Hazen, Melissa] Childrens Hosp Boston, Boston, MA USA. [McArdel, Shannon; Ercan, Alton; Lee, David] Brigham & Womens Hosp, Boston, MA 02115 USA. [McArdel, Shannon; Ercan, Alton; Ortiz-Lopez, Adriana; Benoist, Christophe; Mathis, Diane; Lee, David] Harvard Univ, Sch Med, Boston, MA USA. [Ortiz-Lopez, Adriana; Benoist, Christophe; Mathis, Diane] Joslin Diabet Ctr, Boston, MA 02215 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S118 EP S118 DI 10.1016/j.clim.2009.03.349 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300341 ER PT J AU Kim, SS Peer, D Kumar, P Shimaoka, M Shankar, P AF Kim, Sang-Soo Peer, Dan Kumar, Priti Shimaoka, Motomu Shankar, Premlata TI siRNA Delivery with Integrin LFA-1-targeted Nanoparticles Prevents HIV Infection in Humanized Mice SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Kim, Sang-Soo; Shankar, Premlata] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, El Paso, TX USA. [Peer, Dan; Shimaoka, Motomu] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Kumar, Priti] Yale Univ, Sch Med, New Haven, CT USA. RI Peer, Dan/A-1785-2011 OI Peer, Dan/0000-0001-8238-0673 NR 0 TC 1 Z9 1 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S75 EP S76 DI 10.1016/j.clim.2009.03.221 PG 2 WC Immunology SC Immunology GA 449PK UT WOS:000266342300214 ER PT J AU Moghadam-Kia, S Klein, R Chilek, K Gaines, E Costner, M Rose, M Okawa, J Werth, V AF Moghadam-Kia, Siamak Klein, Rachel Chilek, Katherine Gaines, Elizabeth Costner, Melissa Rose, Mathew Okawa, Joyce Werth, Victoria TI Characteristics of Patients with Refractory Cutaneous Lupus Erythematosus: A Database Analysis of 152 Patients Seen at an Outpatient Dermatology Clinic SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Moghadam-Kia, Siamak; Klein, Rachel; Chilek, Katherine; Gaines, Elizabeth; Rose, Mathew; Okawa, Joyce; Werth, Victoria] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Costner, Melissa] Univ Texas SW, Dallas, TX 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S129 EP S129 DI 10.1016/j.clim.2009.03.382 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300374 ER PT J AU Orban, T Farkas, K Jalahej, H Kis, J Treszl, A Falk, B Reijonen, H Wolfsdorf, J Ricker, A Matthews, J Tchao, N Sayre, P Bianchine, P AF Orban, Tihamer Farkas, Klara Jalahej, Heyam Kis, Janos Treszl, Andras Falk, Ben Reijonen, Helena Wolfsdorf, Joseph Ricker, Alyne Matthews, Jeffrey Tchao, Nadia Sayre, Peter Bianchine, Peter TI Autoantigen Specific Regulatory T Cells Induced in Patients with Type 1 Diabetes Mellitus SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Orban, Tihamer; Farkas, Klara; Jalahej, Heyam] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kis, Janos] Polyclin Hosp Bros, Budapest, Hungary. [Treszl, Andras] Semmelweis Univ, H-1085 Budapest, Hungary. [Falk, Ben; Reijonen, Helena] Virginia Mason, Seattle, WA USA. [Wolfsdorf, Joseph; Ricker, Alyne] Childrens Hosp, Boston, MA 02115 USA. [Matthews, Jeffrey; Tchao, Nadia; Sayre, Peter] UCSF, San Francisco, CA USA. [Bianchine, Peter] NIAID, Bethesda, DC 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 SU S BP S83 EP S83 DI 10.1016/j.clim.2009.03.243 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300236 ER PT J AU Tocco, G Kim, P Kant, C Lin, C Yun, SH Benichou, G AF Tocco, Georges Kim, Pilhan Kant, Cavit Lin, Charles Yun, Seok-Hyun Benichou, Gilles TI Cellular Migration in Transplantation Studied Using in vivo Microscopy SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Tocco, Georges; Kim, Pilhan; Kant, Cavit; Lin, Charles; Yun, Seok-Hyun; Benichou, Gilles] 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S11 EP S12 DI 10.1016/j.clim.2009.03.027 PG 2 WC Immunology SC Immunology GA 449PK UT WOS:000266342300024 ER PT J AU Yip, L Creusot, R Sheng, DQ Chang, P Czesak, M Albert, P Collier, AR Turley, S Fathman, CG Su, L AF Yip, Linda Creusot, Remi Sheng, Deqiao Chang, Pearl Czesak, Margaret Albert, Paul Collier, Ai-ris Turley, Shannon Fathman, C. Garrison Su, Leon TI Deaf1 Isoforms Control Changes in Peripheral Tissue Antigen Gene Expression in the Non-obese Diabetic Mouse Pancreatic Lymph Node during Type I Diabetes Pathogenesis SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 11-14, 2009 CL San Francisco, CA SP Federat Clin Immunol Soc C1 [Yip, Linda; Creusot, Remi; Sheng, Deqiao; Chang, Pearl; Fathman, C. Garrison; Su, Leon] Stanford Univ, Stanford, CA 94305 USA. [Czesak, Margaret; Albert, Paul] Univ Ottawa, Ottawa, ON, Canada. [Collier, Ai-ris; Turley, Shannon] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Albert, Paul/E-4804-2010 OI Albert, Paul/0000-0002-1809-3554 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2009 VL 131 BP S117 EP S117 DI 10.1016/j.clim.2009.03.344 PG 1 WC Immunology SC Immunology GA 449PK UT WOS:000266342300336 ER PT J AU Gist, S Tio-Matos, I Falzgraf, S Cameron, S Beebe, M AF Gist, Steve Tio-Matos, Iris Falzgraf, Sharon Cameron, Shirley Beebe, Michael TI Wound care in the geriatric client SO CLINICAL INTERVENTIONS IN AGING LA English DT Review DE wound care; pressure ulcers; vascular ulcers; diabetic ulcers; debridement; elderly AB With our aging population, chronic diseases that compromise skin integrity such as diabetes, peripheral vascular disease (venous hypertension, arterial insufficiency) are becoming increasingly common. Skin breakdown with ulcer and chronic wound formation is a frequent consequence of these diseases. Types of ulcers include pressure ulcers, vascular ulcers (arterial and venous hypertension), and neuropathic ulcers. Treatment of these ulcers involves recognizing the four stages of healing: coagulation, inflammation, proliferation, and maturation. Chronic wounds are frequently stalled in the inflammatory stage. Moving past the inflammation stage requires considering the bacterial burden, necrotic tissue, and moisture balance of the wound being treated. Bacterial overgrowth or infection needs to be treated with topical or systemic agents. In most cases, necrotic tissue needs to be debrided and moisture balance needs to be addressed by wetting dry tissue and drying wet tissue. Special dressings have been developed to accomplish these tasks. They include films, hydrocolloids, hydrogel dressings, foams, hydrofibers, composite and alginate dressings. C1 VA Puget Sound Hlth Care Syst, Geriatr Program, Amer Lake Div, Tacoma, WA USA. VA Puget Sound Hlth Care Syst, Extended Care Program, Amer Lake Div, Tacoma, WA USA. RP Beebe, M (reprint author), VA Puget Sound Hlth Care Syst, Integrated Geriatr Programs, Tacoma, WA USA. EM michael.beebe@va.gov NR 48 TC 28 Z9 28 U1 1 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9092 J9 CLIN INTERV AGING JI Clin. Interv. Aging PY 2009 VL 4 BP 269 EP 287 PG 19 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA V21WZ UT WOS:000208239000030 PM 19554098 ER PT J AU Niewczas, MA Ficociello, LH Johnson, AC Walker, W Rosolowsky, ET Roshan, B Warram, JH Krolewski, AS AF Niewczas, Monika A. Ficociello, Linda H. Johnson, Amanda C. Walker, William Rosolowsky, Elizabeth T. Roshan, Bijan Warram, James H. Krolewski, Andrzej S. TI Serum Concentrations of Markers of TNF alpha and Fas-Mediated Pathways and Renal Function in Nonproteinuric Patients with Type 1 Diabetes SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; MICROVASCULAR COMPLICATIONS; SOLUBLE RECEPTORS; FUNCTION DECLINE; CYSTATIN-C; INFLAMMATION; APOPTOSIS; MICROALBUMINURIA; NEPHROPATHY; PLASMA AB Background and objectives: The aim of our study was to examine serum markers of the TNF and Fas pathways for association with cystatin-C based estimated glomerular filtration rate (cC-GFR) in subjects with type 1 diabetes (T1DM) and no proteinuria. Design, setting, participants, & measurements: The study group (the 2nd Joslin Kidney Study) comprised patients with T1DM and normoalbuminuria (NA) (n = 363) or microalbuminuria (MA) 01 = 304). Impaired renal function (cC-GFR <90 ml/min) was present in only 10% of patients with NA and 36% of those with MA. We measured markers of the tumor necrosis factor a (TNF alpha) pathway [TNF alpha, soluble TNF receptor 1 (sTNFR1), and 2 (sTNFR2)], its downstream effectors [soluble intercellular and soluble vascular adhesion molecules (sICAM-1 and sVCAM-1), interleukin 8 (IL8/CXCL8), monocytes chemoattractant protein-1 (MCPI), and IFN gamma inducible protein-10 (IP10/CXCL10)], the Fas pathway [soluble Fas (sFas) and Fas ligand (sFasL)], CRP, and IL6. Results: Of these, TNF alpha, sTNFRs, sFas, sICAM-1, and sIP10 were associated with cC-GFR. However, only the TNF receptors and sFas were associated with cC-GFR in multivariate analysis. Variation in the concentration of the TNF receptors had a much stronger impact on GFR than clinical covariates such as age and albumin excretion. Conclusions: Elevated concentrations of serum markers of the TNFa and Fas-pathways are strongly associated with decreased renal function in nonproteinuric type 1 diabetic patients. These effects are independent of those of urinary albumin excretion. Follow-up studies are needed to characterize the role of these markers in early progressive renal function decline. C1 [Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Niewczas, Monika A.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Niewczas, Monika A.] Warsaw Med Univ, Dept Immunol Transplant Med & Internal Dis, Warsaw, Poland. [Rosolowsky, Elizabeth T.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU National Institutes of Health [DK-41526]; American Diabetes Association mentor-based fellowship; [7-03-MN-28] FX M.A. Niewczas was supported by Americal Diabetes Association mentor-based fellowship # 7-03-MN-28. The authors thank Harry Spaulding for his assistance in the preparation of this manuscript. NR 37 TC 72 Z9 87 U1 2 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2009 VL 4 IS 1 BP 62 EP 70 DI 10.2215/CJN.03010608 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 397SA UT WOS:000262681200012 PM 19073786 ER PT J AU Chakkera, HA Chertow, GM O'Hare, AM Amend, WJ Gonwa, TA AF Chakkera, Harini A. Chertow, Glenn M. O'Hare, Ann M. Amend, William J., Jr. Gonwa, Thomas A. TI Regional Variation in Kidney Transplant Outcomes: Trends Over Time SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID UNITED-STATES; VASCULAR ACCESS; HEMODIALYSIS; VARIABILITY; MANAGEMENT; SURGERY; US AB Background and objectives: Clinical outcomes after kidney transplant have improved considerably in the United States over the past several decades. However, the degree to which this has occurred uniformly across the country is unknown. Design, setting, participants, & measurements: Regional variations in graft failure after kidney transplant during three different time periods were examined. These time periods were chosen to coincide with major shifts in immunosuppressant usage: Era 1, cyclosporine usage, 3.988 through 1989; Era 2, introduction of tacrolimus and mycophenolate mofetil, 1994 through 1995; and Era 3, widespread use of tacrolimus and mycophenolate mofetil, 1998 through 1999. Patient data were obtained from the United States Renal Data System database. For each period, regional differences in time from transplant to graft failure (organ removal, death, or return to dialysis) were examined. For each region, differences in graft failure over time were examined. Results: One-year graft survival rates ranged from 76% to 83% between regions in Era 1 (n = 13,669), from 84% to 89% in Era 2 (n = 17,456), and from 87.5%, to 92% in Era 3 (n = 20,375). Three-year graft survival ranged from 65% to 75% between regions in Era 1, from 84% to 89% in Era 2, and from 77% to 86%) in Era 3. Adjusted models for donor and recipient characteristics showed improvements in graft survival over time in all United Network for Organ Sharing regions with minimal variation across regions. Conclusions: Regional differences in graft survival after kidney transplant are minimal, particularly when compared with the dramatic improvements in graft survival that have occurred over time. C1 [Chakkera, Harini A.] Mayo Clin, Div Transplant Med, Scottsdale, AZ USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [O'Hare, Ann M.] Univ Washington, Sch Med, Div Nephrol, Seattle, WA USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Amend, William J., Jr.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Gonwa, Thomas A.] Mayo Clin, Div Transplant Med, Jacksonville, FL 32224 USA. RP Chakkera, HA (reprint author), Mayo Clin Hosp, Div Transplantat, MCSB, 5777 E Mayo Blvd, Phoenix, AZ 85054 USA. EM chakkera.harini@mayo.edu FU Health Resources and Services Administration [234-2005-370011C] FX This,vas Supported in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility Of the authors alone and does not necessarily reflect the view of the Department of Health and Human Services. NR 18 TC 5 Z9 6 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2009 VL 4 IS 1 BP 152 EP 159 DI 10.2215/CJN.02050408 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 397SA UT WOS:000262681200024 PM 18922989 ER PT J AU Pekkala, S Goral, M Hyun, J Obler, LK Erkinjuntti, T Albert, ML AF Pekkala, Seija Goral, Mira Hyun, Jungmoon Obler, Loraine K. Erkinjuntti, Timo Albert, Martin L. TI Semantic verbal fluency in two contrasting languages SO CLINICAL LINGUISTICS & PHONETICS LA English DT Article DE Semantic verbal fluency; culture; language; cross-language; older adults ID CERAD NEUROPSYCHOLOGICAL BATTERY; CATEGORY FLUENCY; ALZHEIMERS-DISEASE; NORMATIVE DATA; VASCULAR DEMENTIA; CULTURE; AGE; MEMORY; EDUCATION; PERFORMANCE AB This cross-linguistic study investigated Semantic Verbal Fluency (SVF) performance in 30 American English-speaking and 30 Finnish-speaking healthy elderly adults with different cultural and linguistic backgrounds. Despite the different backgrounds of the participant groups, remarkable similarities were found between the groups in the overall SVF performance in two semantic categories (animals and clothes), in the proportions of words produced within the first half (30 seconds) of the SVF tasks, and in the variety of words produced for the categories. These similarities emerged despite the difference in the mean length of words produced in the two languages (with Finnish words being significantly longer than English words). The few differences found between the groups concerned the types and frequencies of the 10 most common words generated for the categories. It was concluded that culture and language differences do not contribute significantly to variability in SVF performance in healthy elderly people. C1 [Pekkala, Seija] Univ Helsinki, Dept Speech Sci, FIN-00014 Helsinki, Finland. [Goral, Mira; Hyun, Jungmoon; Obler, Loraine K.] CUNY, Grad Ctr, Program Speech Language Hearning Sci, New York, NY USA. [Goral, Mira; Hyun, Jungmoon; Obler, Loraine K.; Albert, Martin L.] VA Boston Healthcare Syst, Med Res Serv, Boston, MA USA. [Goral, Mira] CUNY, Lehman Coll, New York, NY 10021 USA. [Obler, Loraine K.; Albert, Martin L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Erkinjuntti, Timo] Univ Helsinki, Dept Neurol, Helsinki, Finland. RP Pekkala, S (reprint author), Univ Helsinki, Dept Speech Sci, POB 9,Siltavuorenpenger 20 A, FIN-00014 Helsinki, Finland. EM seija.pekkala@helsinki.fi FU NIA NIH HHS [R01 AG014345, R01 AG014345-10, AG14345] NR 57 TC 7 Z9 8 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9206 J9 CLIN LINGUIST PHONET JI Clin. Linguist. Phon. PY 2009 VL 23 IS 6 BP 431 EP 445 DI 10.1080/02699200902839800 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 454YR UT WOS:000266720900003 PM 19440894 ER PT J AU Herbst, RS Lynch, TJ Sandler, AB AF Herbst, Roy S. Lynch, Thomas J. Sandler, Alan B. TI Beyond Doublet Chemotherapy for Advanced Non-Small-Cell Lung Cancer: Combination of Targeted Agents with First-Line Chemotherapy SO CLINICAL LUNG CANCER LA English DT Review DE Epidermal growth factor receptor; Farnesyltransferase inhibitors; Protein kinase C; Tyrosine kinase ID PHASE-III TRIAL; GROWTH-FACTOR RECEPTOR; METALLOPROTEINASE INHIBITOR BMS-275291; QUALITY-OF-LIFE; RANDOMIZED-TRIAL; CLINICAL-TRIALS; PLUS CARBOPLATIN; SUPPORTIVE CARE; SINGLE-AGENT; MATRIX METALLOPROTEINASES AB The first-line treatment of advanced non-small-cell lung cancer (NSCLC) has evolved significantly over the past 5 years. As recently as 15 years ago, best supportive care (BSC) was considered an acceptable option for most patients with advanced or metastatic NSCLC, based on the concern that toxic effects of systemic chemotherapy overshadowed any potential benefits. The enhanced efficacy of platinum-based doublet chemotherapeutic regimens led to increases in overall patient survival relative to BSC. However, overall survival (OS) appeared to plateau, even with the introduction and refinement of these regimens. The addition of novel targeted agents targeting growth pathways to platinum-based regimens failed to overcome the 7.8- to 10.5-month survival barrier. After many phase III clinical trials, which involved tyrosine kinase inhibitors, matrix metalloproteinase inhibitors, protein kinase C inhibitors, and retinoids, this survival barrier had yet to be surmounted, although in some cases certain subgroups benefited, suggesting specific molecular correlations. Recently, inhibition of components of the angiogenesis pathway with the addition of bevacizumab to a platinum-based doublet led to statistically significant increases in OS, progression-free survival, and response rate relative to chemotherapy alone. This advance pushed the median survival of selected patients with advanced or metastatic NSCLC who met the eligibility criteria of the trial over the 12-month mark, thus offering patients and clinicians hope for more incremental advances in the future. C1 [Herbst, Roy S.] Univ Texas MD Anderson Canc Ctr, Sect Thorac Med Oncol, Houston, TX 77030 USA. [Lynch, Thomas J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sandler, Alan B.] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. RP Herbst, RS (reprint author), Univ Texas MD Anderson Canc Ctr, Sect Thorac Med Oncol, 1515 Holcombe Blvd,Unit 432, Houston, TX 77030 USA. EM rherbst@mdanderson.org NR 91 TC 11 Z9 11 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JAN PY 2009 VL 10 IS 1 BP 20 EP 27 DI 10.3816/CLC.2009.n.003 PG 8 WC Oncology SC Oncology GA 406TW UT WOS:000263318800003 PM 19289368 ER PT J AU Iverson, GL Langlois, JA McCrea, MA Kelly, JP AF Iverson, Grant L. Langlois, Jean A. McCrea, Michael A. Kelly, James P. TI CHALLENGES ASSOCIATED WITH POST-DEPLOYMENT SCREENING FOR MILD TRAUMATIC BRAIN INJURY IN MILITARY PERSONNEL SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Mild Traumatic Brain Injury; Military; Screening; Epidemiology ID POSTCONCUSSIVE SYMPTOMS; CHRONIC PAIN; CONCUSSION; IRAQ; METAANALYSIS; AFGHANISTAN; DISORDER; CARE AB There is ongoing debate regarding the epidemiology of mild traumatic brain injury (MTBI) in military personnel. Accurate and timely estimates of the incidence of brain injury and the prevalence of long-term problems associated with brain injuries among active duty service members and veterans are essential for (a) operational planning, and (b) to allocate sufficient resources for rehabilitation and ongoing services and supports. The purpose of this article is to discuss challenges associated with post-deployment screening for MTBI. Multiple screening methods have been used in military, Veterans Affairs, and independent studies, which complicate cross-study comparisons of the resulting epidemiological data. We believe that post-deployment screening is important and necessary-but no screening methodology will be flawless, and false positives and false negatives are inevitable. Additional research is necessary to refine the sequential screening methodology, with the goal of minimizing false negatives during initial post-deployment screening and minimizing false positives during follow-up evaluations. C1 [Iverson, Grant L.] Univ British Columbia, Dept Psychiat, Vancouver, BC V6T 2A1, Canada. [Iverson, Grant L.] British Columbia Mental Hlth & Addict Serv, Vancouver, BC, Canada. [Langlois, Jean A.] US Dept Vet Affairs, Off Res & Dev, Washington, DC USA. [McCrea, Michael A.] Waukesha Mem Hosp, Ctr Neurosci, Waukesha, WI USA. [McCrea, Michael A.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Kelly, James P.] Univ Colorado, Dept Neurosurg, Denver Sch Med, Denver, CO 80202 USA. [Kelly, James P.] Univ Colorado, Dept Phys Med & Rehabil, Denver Sch Med, Denver, CO 80202 USA. [Kelly, James P.] Def Ctr Excellence Psychol Hlth, Natl Intrepid Ctr Excellence, Washington, DC USA. [Kelly, James P.] US Dept Def, TBI, Washington, DC 20305 USA. RP Iverson, GL (reprint author), Univ British Columbia, Dept Psychiat, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada. EM giverson@interchange.ubc.ca NR 24 TC 52 Z9 52 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2009 VL 23 IS 8 BP 1299 EP 1314 DI 10.1080/13854040903153902 PG 16 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 524KF UT WOS:000272141500005 PM 19882473 ER PT J AU Harris, WH AF Harris, William H. TI The First 50 Years of Total Hip Arthroplasty: Lessons Learned SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 36th Open Meeting of the Hip-Society CY MAR 08, 2008 CL San Francisco, CA SP Hip So ID POLYETHYLENE ACETABULAR COMPONENTS; MOLECULAR-WEIGHT POLYETHYLENE; CROSS-LINKED POLYETHYLENE; FOLLOW-UP; WEAR PRODUCTS; REPLACEMENT; REVISION; BONE; OSTEOLYSIS; CEMENT AB Fifty years have passed since the first total hip arthroplasty of the modern era was performed. At this, the vantage point, it is reasonable to review these five decades, inquiring behind the single dominating observation that, in its current form, this operation is one of the most successful of all surgical procedures for the management of end-stage human disease. What are the generic lessons that can be derived from the experience? Succinctly, five major observations appear valuable. They are "skunk works," "Pasteur's motto," "the totally unexpected," "research solutions," and "the role of alternatives." "Skunk works," an industrial management term, might be characterized as an innovative endeavor that is offline and off-budget resulting from the relentless pursuit of a vivid dream by creative zealots who eschew defeat. Pasteur's motto dealt with serendipity, which was crucial to total hip arthroplasty progress. The totally unexpected is represented by an entirely new manmade disease, "periprosthetic osteolysis." The research solutions are represented by the complex, sophisticated contemporary research that has unraveled periprosthetic osteolysis and suggested modes of correction. Finally, the application of "alternatives" has characterized major progress. Importantly, these, or similar generic observations, may provide insights into important progress in the future. C1 [Harris, William H.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. [Harris, William H.] Massachusetts Gen Hosp, Adult Reconstruct Unit, Boston, MA 02114 USA. [Harris, William H.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM wharrishm@hotmail.com NR 25 TC 15 Z9 17 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2009 VL 467 IS 1 BP 28 EP 31 DI 10.1007/s11999-008-0467-1 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 383RH UT WOS:000261690600004 PM 18982399 ER PT J AU McCarthy, JC Jibodh, SR Lee, JA AF McCarthy, Joseph C. Jibodh, Stefan R. Lee, Jo-Ann TI The Role of Arthroscopy in Evaluation of Painful Hip Arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 36th Open Meeting of the Hip-Society CY MAR 08, 2008 CL San Francisco, CA SP Hip So ID TOTAL KNEE ARTHROPLASTY; REPLACEMENT AB Unexplained pain after hip arthroplasty is frustrating for patients and surgeons. We describe the use of hip arthroscopy in management of the painful hip arthroplasty, critically evaluate the outcomes of these patients, and refine indications for hip arthroscopy in this setting. We retrospectively reviewed 14 patients (16 hips) who underwent hip arthroscopy after joint replacement. One patient had suspected septic arthritis despite negative aspiration and one had known septic arthritis but was not a candidate for open arthrotomy; two had intraarticular migration of hardware. The remaining 10 patients (11 hips) had persistent pain despite negative diagnostic studies. The two patients (two hips) with infection were successfully treated with arthroscopic lavage and d,bridement plus intravenous antibiotics. Intraarticular metal fragments and a loose acetabular screw were successfully removed in two patients (three hips). Findings in the remaining 11 hips included a loose acetabular component (one); corrosion at the head-neck junction of a metal-on-metal articulation (one); soft tissue-scar impingement at the head/cup interface (four); synovitis with associated scar tissue (four); and capsular scarring with adhesions (one). Arthroscopy represented a successful treatment or directly led to a successful treatment in 12 of 16 hips. We observed no complications as a result of the arthroscopy. Arthroscopy may be of value in selected patients undergoing hip arthroplasty with unexplained pain after an inconclusive standard workup. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. C1 [McCarthy, Joseph C.; Lee, Jo-Ann] Newton Wellesley Hosp, Dept Orthopaed Surg, Newton, MA 02462 USA. [McCarthy, Joseph C.; Jibodh, Stefan R.; Lee, Jo-Ann] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP McCarthy, JC (reprint author), Newton Wellesley Hosp, Dept Orthopaed Surg, 2000 Washington St,Green 361, Newton, MA 02462 USA. EM jcmccarthy1@partners.org NR 21 TC 16 Z9 19 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2009 VL 467 IS 1 BP 174 EP 180 DI 10.1007/s11999-008-0525-8 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 383RH UT WOS:000261690600023 PM 18830795 ER PT J AU Johnson, DC Campbell, SL Rabkin, JD AF Johnson, Douglas Clark Campbell, Stacy Lynn Rabkin, Judith Dawn TI Tracheostomy tube manometry: evaluation of speaking valves, capping and need for downsizing SO CLINICAL RESPIRATORY JOURNAL LA English DT Article DE dyspnea; manometry; speaking valve; speech; tracheostomy tube AB Readiness to speak is a major problem for many tracheostomized patients. Evaluation for tracheostomy tube capping or speaking valve is often subjective. We first wanted to assess whether there were differences among speaking valves. We developed a care pathway for tracheostomy tube evaluation and management including manometry, which we wanted to evaluate. Three different speaking valves were assessed using manometry and measuring dyspnea in 21 patients. Subsequently, 100 consecutive patients referred for tracheostomy tube evaluation in a long-term acute-care rehabilitation hospital were studied using our care pathway with manometry before and after tracheostomy tube changes. Inspiratory pressures differed among the speaking valves. Borg scale was higher among patients with high expiratory pressures. Of the 100 patients, following our care pathway, speech (speaking valve or capping) was recommended for 78 patients with their initial tube, and for 93 patients within 2 days of their initial evaluation. Tracheostomy tube downsizing was recommended in 94 patients. Downsizing led to significant reductions in airway pressures. Capping was initially recommended for 12 patients and for 71 following downsizing. Women had higher pressures than men for the same size tubes. Tracheostomy tube manometry is very helpful in objectively guiding recommendations for speaking valve use, capping, and changing tracheostomy tubes. Speech is an early recommendation for most patients. Please cite this paper as: Johnson DC, Campbell SL and Rabkin JD. Tracheostomy tube manometry: evaluation of speaking valves, capping and need for downsizing. The Clinical Respiratory Journal 2009; 3: 8-14. C1 [Johnson, Douglas Clark; Rabkin, Judith Dawn] Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Campbell, Stacy Lynn] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Johnson, DC (reprint author), Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. EM djohnson5@partners.org NR 9 TC 6 Z9 6 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-6981 J9 CLIN RESPIR J JI Clin. Respir. J. PD JAN PY 2009 VL 3 IS 1 BP 8 EP 14 DI 10.1111/j.1752-699X.2008.00100.x PG 7 WC Respiratory System SC Respiratory System GA 381FO UT WOS:000261521300003 PM 20298366 ER PT J AU Jin, WZ Patti, ME AF Jin, Wanzhu Patti, Mary-Elizabeth TI Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes SO CLINICAL SCIENCE LA English DT Review DE endoplasmic reticulum stress; inflammation; mitochondrion; obesity; pancreatic beta-cell; Type 2 diabetes ID GENOME-WIDE ASSOCIATION; LOW-BIRTH-WEIGHT; PANCREATIC BETA-CELLS; ENDOPLASMIC-RETICULUM STRESS; IMPAIRED GLUCOSE-TOLERANCE; INDUCED INSULIN-RESISTANCE; OXIDATIVE ENZYME-ACTIVITY; HUMAN SKELETAL-MUSCLE; ADIPOSE-TISSUE; IN-VIVO AB T2DM (Type 2 diabetes mellitus) has reached epidemic proportions worldwide, exerting major health consequences at an individual and public health level alike. Unfortunately, the molecular pathophysiology of diabetes remains incompletely understood, impairing progress towards more effective prevention and treatment strategies. Although the rapid increase in the prevalence of insulin resistance and T2DM over the past several decades highlights a major environmental contribution related to overnutrition, obesity and inactivity, susceptibility is likely to reflect individual differences in complex gene-environment interactions. In the present review, we focus on mediators of genetic and environmental risk for T2DM at a molecular level. C1 [Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU National Institutes of Health [DK062948, DK060837]; Graetz Fund FX We gratefully acknowledge research support from the National Institutes of Health [grant numbers DK062948, DK060837 (to M.-E.P.)]; and the Graetz Fund. NR 154 TC 31 Z9 35 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD JAN PY 2009 VL 116 IS 1-2 BP 99 EP 111 DI 10.1042/CS20080090 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 391DG UT WOS:000262212900012 PM 19076063 ER PT J AU Sims, K Politei, J Banikazemi, M Lee, P AF Sims, K. Politei, J. Banikazemi, M. Lee, P. TI CHARACTERIZATION AND INCIDENCE OF STROKE IN FABRY DISEASE: ANALYSIS OF NATURAL HISTORY DATA FROM THE FABRY REGISTRY SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 9th Annual European Round Table Meeting on Fabry Disease CY OCT 17-18, 2008 CL Athens, GREECE SP Genzyme Europe BV C1 [Sims, K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sims, K.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Politei, J.] Juan Fernandez Hosp, Neurol Serv, Buenos Aires, DF, Argentina. [Banikazemi, M.] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA. [Banikazemi, M.] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. [Lee, P.] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2009 VL 31 BP S31 EP S31 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 475HJ UT WOS:000268348900023 ER PT J AU Sims, KB AF Sims, Katherine B. TI The Fabry Registry: Looking at Tomorrow SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 9th Annual European Round Table Meeting on Fabry Disease CY OCT 17-18, 2008 CL Athens, GREECE SP Genzyme Europe BV ID DISEASE; FEMALES; INVOLVEMENT; MALES C1 [Sims, Katherine B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sims, Katherine B.] Harvard Univ, Sch Med, Boston, MA USA. EM ksims@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2009 VL 31 BP S22 EP S23 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 475HJ UT WOS:000268348900014 ER PT B AU Chad, DA Siao, P AF Chad, David A. Siao, Peter BE Stone, JH TI Vasculitic Neuropathy SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID PERIPHERAL NEUROPATHY; NERVE; DIAGNOSIS; BIOPSY C1 [Chad, David A.; Siao, Peter] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chad, DA (reprint author), Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St,Suite 820, Boston, MA 02114 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 211 EP 218 DI 10.1007/978-1-84800-934-9_20 PG 8 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400020 ER PT B AU Churg, A Specks, U Stone, JH AF Churg, Andrew Specks, Ulrich Stone, John H. BE Stone, JH TI The Churg-Strauss Syndrome SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; HYPEREOSINOPHILIC SYNDROME; ASTHMA C1 [Churg, Andrew] Univ British Columbia, Dept Pathol, Vancouver, BC V6T 2B5, Canada. [Specks, Ulrich] May Clin, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. RP Churg, A (reprint author), Univ British Columbia, Dept Pathol, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 239 EP 244 DI 10.1007/978-1-84800-934-9_23 PG 6 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400023 ER PT B AU Stone, JH Ozaki, S Keogh, K Specks, U Langford, CA Rasmussen, N Kallenberg, CGM Bajema, IM AF Stone, John H. Ozaki, Shoichi Keogh, Karina Specks, Ulrich Langford, Carol A. Rasmussen, Niels Kallenberg, Cees G. M. Bajema, Ingeborg M. BE Stone, JH TI ANCA-Associated Vasculitis SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; SMALL-VESSEL VASCULITIS; OF-THE-LITERATURE; WEGENERS-GRANULOMATOSIS; CRESCENTIC GLOMERULONEPHRITIS; MICROSCOPIC POLYANGIITIS; SYSTEMIC VASCULITIS; RENAL-TRANSPLANTATION; RANDOMIZED-TRIAL; DISEASE C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. [Ozaki, Shoichi] St Marianna Univ, Sch Med, Dept Internal Med, Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan. [Keogh, Karina; Specks, Ulrich] May Clin, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. [Langford, Carol A.] Cleveland Clin Fdn, Dept Rheumatol & Immunol, Cleveland, OH 44195 USA. [Rasmussen, Niels] Rigshosp, DK-2100 Copenhagen, Denmark. [Kallenberg, Cees G. M.] Univ Med Groningen Clin Immunol Rheumatol, NL-9713 GZ Groningen, Netherlands. [Bajema, Ingeborg M.] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin, 55 Fruit St,Yawkey 2, Boston, MA 02114 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 245 EP 267 DI 10.1007/978-1-84800-934-9_24 PG 23 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400024 ER PT B AU Stone, JH AF Stone, John H. BE Stone, JH TI Polyarteritis Nodosa SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID ANTIPHOSPHOLIPID SYNDROME; LIVEDOID VASCULOPATHY; MICROSCOPIC POLYANGIITIS; PERIPHERAL NEUROPATHY; SNEDDON-SYNDROME; WOMAN; DISEASE; BIOPSY; SKIN; ANTIBODIES C1 Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin, 55 Fruit St,Yawkey 2, Boston, MA 02114 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 275 EP 284 DI 10.1007/978-1-84800-934-9_26 PG 10 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400026 ER PT B AU Stone, JR Pless, M Salvarani, C Pipitone, N Lessell, S Stone, JH AF Stone, James R. Pless, Misha Salvarani, Carlo Pipitone, Nicolo Lessell, Simmons Stone, John H. BE Stone, JH TI Giant Cell Arteritis and Polymyalgia Rheumatica SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID PLACEBO-CONTROLLED TRIAL; POSITRON-EMISSION-TOMOGRAPHY; SUPERFICIAL TEMPORAL ARTERY; LARGE-VESSEL VASCULITIS; CORTICOSTEROID TREATMENT; DOUBLE-BLIND; ANTICARDIOLIPIN ANTIBODIES; DUPLEX ULTRASONOGRAPHY; OCULAR MANIFESTATIONS; ANTICOAGULANT-THERAPY C1 [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. [Salvarani, Carlo; Pipitone, Nicolo] Areispedale S Maria Nuova, I-42100 Reggio Emilia, Italy. [Pless, Misha] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lessell, Simmons] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. OI Salvarani, Carlo/0000-0001-5426-5133 NR 86 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 285 EP 304 DI 10.1007/978-1-84800-934-9_27 PG 20 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400027 ER PT B AU Molloy, ES Stone, JH Langford, CA AF Molloy, Eamonn S. Stone, John H. Langford, Carol A. BE Stone, JH TI Takayasu's Arteritis SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID NECROSIS FACTOR THERAPY; SURGICAL-TREATMENT; FOLLOW-UP; LIMITATIONS; DIAGNOSIS; DISEASE; COHORT C1 [Molloy, Eamonn S.] Cleveland Clin, Cleveland, OH 44195 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. [Langford, Carol A.] Cleveland Clin Fdn, Dept Rheumatol & Immunol, Cleveland, OH 44195 USA. RP Molloy, ES (reprint author), Cleveland Clin, Desk A50,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 305 EP 310 DI 10.1007/978-1-84800-934-9_28 PG 6 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400028 ER PT B AU Calabrese, LH Singhal, AB AF Calabrese, Leonard H. Singhal, Aneesh B. BE Stone, JH TI Primary Angiitis of the Central Nervous System and Reversible Cerebral Vasoconstriction Syndromes SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID THUNDERCLAP HEADACHE; VASCULITIS; ANGIOPATHY; BIOPSY C1 [Calabrese, Leonard H.] Cleveland Clin Fdn, Dept Rheumatol & Immunol, Cleveland, OH 44195 USA. [Singhal, Aneesh B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Stroke Res Ctr, Boston, MA 02114 USA. RP Calabrese, LH (reprint author), Cleveland Clin Fdn, Dept Rheumatol & Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 311 EP 316 DI 10.1007/978-1-84800-934-9_29 PG 6 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400029 ER PT B AU Matteson, EL Stone, JH AF Matteson, Eric L. Stone, John H. BE Stone, JH TI Thromboangiitis Obliterans (Buerger's Disease) SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID TOBACCO C1 [Matteson, Eric L.] Mayo Clin, Div Rheumatol, Rochester, MN 55095 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. RP Matteson, EL (reprint author), Mayo Clin, Div Rheumatol, 200 1st St SW, Rochester, MN 55095 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 317 EP 323 DI 10.1007/978-1-84800-934-9_30 PG 7 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400030 ER PT B AU Matteson, EL Stone, JH AF Matteson, Eric L. Stone, John H. BE Stone, JH TI Less Common Forms of Vasculitis SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID ERYTHEMA-ELEVATUM-DIUTINUM; URTICARIAL VASCULITIS; COGANS-SYNDROME C1 [Matteson, Eric L.] Mayo Clin, Div Rheumatol, Rochester, MN 55095 USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. RP Matteson, EL (reprint author), Mayo Clin, Div Rheumatol, 200 1st St SW, Rochester, MN 55095 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 325 EP 333 DI 10.1007/978-1-84800-934-9_31 PG 9 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400031 ER PT B AU Rosenbaum, JT Papaliodis, GN AF Rosenbaum, James T. Papaliodis, George N. BE Stone, JH TI Inflammatory Eye Disease SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID GIANT-CELL ARTERITIS; ERYTHROCYTE SEDIMENTATION-RATE; TUBULOINTERSTITIAL NEPHRITIS; PARS PLANITIS; UVEITIS; PROGNOSIS; COMPLICATIONS; VASCULITIS; SCLERITIS; ARTHRITIS C1 [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Div Arthrit & Rheumat Dis, Casey Eye Inst, Portland, OR 97239 USA. [Papaliodis, George N.] Massachusetts Eye & Ear Infirm, Ocular Immunol Clin, Boston, MA 02114 USA. RP Rosenbaum, JT (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, Div Arthrit & Rheumat Dis, Casey Eye Inst, 2275 SW Terwilliger Blvd, Portland, OR 97239 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 377 EP 384 DI 10.1007/979-1-84800-934-9_38 PG 8 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400038 ER PT B AU Seton, M AF Seton, Margaret BE Stone, JH TI Paget's Disease of Bone SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID ZOLEDRONIC ACID; ETIDRONATE; RISEDRONATE; SEQUESTOSOME-1; MUTATION; TERM; ALENDRONATE; IMPROVEMENT; DISODIUM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Seton, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 405 EP 408 DI 10.1007/978-1-84800-934-9_41 PG 4 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400041 ER PT B AU Dixit, RK Schwab, JH AF Dixit, Rajiv K. Schwab, Joseph H. BE Stone, JH TI Low Back and Neck Pain SO CLINICIAN'S PEARLS AND MYTHS IN RHEUMATOLOGY LA English DT Article; Book Chapter ID LUMBAR SPINAL STENOSIS; RANDOMIZED CONTROLLED-TRIAL; NONOPERATIVE TREATMENT; NONSURGICAL TREATMENT; DISK HERNIATION; FUSION; EXERCISES; SURGERY; SPORT C1 [Dixit, Rajiv K.] Univ Calif San Francisco, Dept Med, Walnut Creek, CA 94598 USA. [Schwab, Joseph H.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Dixit, RK (reprint author), Univ Calif San Francisco, Dept Med, 120 Casa Via,Suite 204, Walnut Creek, CA 94598 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84800-933-2 PY 2009 BP 447 EP 459 DI 10.1007/978-1-84800-934-9_45 PG 13 WC Rheumatology SC Rheumatology GA BMM83 UT WOS:000272857400045 ER PT J AU Salemi, VMC Fernandes, F Sirvente, R Nastari, L Rosa, LV Ferreira, CA Pena, JLB Picard, MH Mady, C AF Cury Salemi, Vera Maria Fernandes, Fabio Sirvente, Raquel Nastari, Luciano Rosa, Leonardo Vieira Ferreira, Cristiano A. Barros Pena, Jose Luiz Picard, Michael H. Mady, Charles TI DOES QUANTITATIVE LEFT VENTRICULAR REGIONAL WALL MOTION CHANGE AFTER FIBROUS TISSUE RESECTION IN ENDOMYOCARDIAL FIBROSIS? SO Clinics LA English DT Article DE Endomyocardial fibrosis; Wall motion; Restrictive cardiomyopathy; Ejection fraction; Surgery ID CARDIOMYOPATHY; EPIDEMIOLOGY; SURVIVAL; AFRICA; VOLUME AB OBJECTIVES: We compared left ventricular regional wall motion, the global left ventricular ejection fraction, and the New York Heart Association functional class pre- and postoperatively. INTRODUCTION: Endomyocardial fibrosis is characterized by fibrous tissue deposition in the endomyocardium of the apex and/or inflow tract of one or both ventricles. Although left ventricular global systolic function is preserved, patients exhibit wall motion abnormalities in the apical and inferoapical regions. Fibrous tissue resection in New York Heart Association FC III and IV endomyocardial fibrosis patients has been shown to decrease morbidity and mortality. METHODS: We prospectively studied 30 patients (20 female, 30+/-10 years) before and 5+/-8 months after surgery. The left ventricular ejection fraction was determined using the area-length method. Regional left ventricular motion was measured by the centerline method. Five left ventricular segments were analyzed pre- and postoperatively. Abnormality was expressed in units of standard deviation from the mean motion in a normal reference population. RESULTS: Left ventricular wall motion in the five regions did not differ between pre- and postoperative measurements. Additionally, the left ventricular ejection fraction did not change after surgery (0.45+/-0.13% x 0.43+/-0.12% pre- and postoperatively, respectively). The New York Heart Association functional class improved to class I in 40% and class II in 43% of patients postoperatively (p < 0.05). CONCLUSIONS: Although endomyocardial fibrosis patients have improved clinical symptoms after surgery, the global left ventricular ejection fraction and regional wall motion in these patients do not change. This finding suggests that other explanations, such as improvements in diastolic function, may be operational. C1 [Cury Salemi, Vera Maria; Fernandes, Fabio; Sirvente, Raquel; Nastari, Luciano; Rosa, Leonardo Vieira; Ferreira, Cristiano A.; Barros Pena, Jose Luiz; Mady, Charles] Univ Sao Paulo, Fac Med, Hosp Clin, Heart Inst InCor,Cardiomyopathy Unit, BR-05508 Sao Paulo, Brazil. [Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Salemi, VMC (reprint author), Univ Sao Paulo, Fac Med, Hosp Clin, Heart Inst InCor,Cardiomyopathy Unit, BR-05508 Sao Paulo, Brazil. EM verasalemi@uol.com.br RI Fernandes, Fabio/D-5994-2012; Sirvente, Raquel/E-6763-2012; Nastari, Luciano/C-8528-2012; Mady, Charles/C-8870-2012; OI Nastari, Luciano/0000-0002-7959-3827; Mady, Charles/0000-0002-8838-199X; Picard, Michael/0000-0002-9264-3243 NR 31 TC 1 Z9 1 U1 0 U2 0 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2009 VL 64 IS 1 BP 17 EP 22 DI 10.1590/S1807-59322009000100004 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 394EX UT WOS:000262429800004 PM 19142546 ER PT J AU Henriques, SG Fraguas, R Iosifescu, DV Menezes, PR de Lucia, MCS Gattaz, WF Martins, MA AF Henriques, Sergio Goncalves Fraguas, Renerio Iosifescu, Dan V. Menezes, Paulo Rossi Souza de Lucia, Mara Cristina Gattaz, Wagner Farid Martins, Milton Arruda TI RECOGNITION OF DEPRESSIVE SYMPTOMS BY PHYSICIANS SO CLINICS LA English DT Article DE Internal medicine; Ambulatory care; Diagnosis; Depressive disorder; Primary care ID PRIMARY-CARE; MAJOR DEPRESSION; MENTAL-DISORDERS; GENERAL-PRACTICE; ATTRIBUTION; EDUCATION; ANXIETY; PREVALENCE; MANAGEMENT; PROJECT AB OBJECTIVE: To investigate the recognition of depressive symptoms of major depressive disorder (MDD) by general practitioners. INTRODUCTION: MDD is underdiagnosed in medical settings, possibly because of difficulties in the recognition of specific depressive symptoms. METHODS: A cross-sectional study of 316 outpatients at their first visit to a teaching general hospital. We evaluated the performance of 19 general practitioners using Primary Care Evaluation of Mental Disorders (PRIME-MD) to detect depressive symptoms and compared them to 11 psychiatrists using Structured Clinical Interview Axis I Disorders, Patient Version (SCID I/P). We measured likelihood ratios, sensitivity, specificity, and false positive and false negative frequencies. RESULTS: The lowest positive likelihood ratios were for psychomotor agitation/retardation (1.6) and fatigue (1.7), mostly because of a high rate of false positive results. The highest positive likelihood ratio was found for thoughts of suicide (8.5). The lowest sensitivity, 61.8%, was found for impaired concentration. The sensitivity for worthlessness or guilt in patients with medical illness was 67.2% (95% CI, 57.4-76.9%), which is significantly lower than that found in patients without medical illness, 91.3% (95% CI, 83.2-99.4%). DISCUSSION: Less adequately identified depressive symptoms were both psychological and somatic in nature. The presence of a medical illness may decrease the sensitivity of recognizing specific depressive symptoms. CONCLUSIONS: Programs for training physicians in the use of diagnostic tools should consider their performance in recognizing specific depressive symptoms. Such procedures could allow for the development of specific training to aid in the detection of the most misrecognized depressive symptoms. C1 [Henriques, Sergio Goncalves; Fraguas, Renerio; Gattaz, Wagner Farid] Univ Sao Paulo, Fac Med, Dept Psychiat, Hosp Clin, Sao Paulo, Brazil. [Henriques, Sergio Goncalves; Fraguas, Renerio; Gattaz, Wagner Farid] Univ Sao Paulo, Fac Med, Inst Psychiat, Hosp Clin, Sao Paulo, Brazil. [Iosifescu, Dan V.] Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02115 USA. [Menezes, Paulo Rossi] Univ Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo, Brazil. [Souza de Lucia, Mara Cristina] Univ Sao Paulo, Fac Med, Div Psychol, Hosp Clin, Sao Paulo, Brazil. [Martins, Milton Arruda] Univ Sao Paulo, Fac Med, Dept Clin Med, Hosp Clin, Sao Paulo, Brazil. RP Henriques, SG (reprint author), Univ Sao Paulo, Fac Med, Dept Psychiat, Hosp Clin, Sao Paulo, Brazil. EM nupi1968@hotmail.com RI Menezes, Paulo/C-9985-2010; Martins, Milton/D-6658-2012; Gattaz, Wagner/C-4456-2012 OI Menezes, Paulo/0000-0001-6330-3314; FU State of Sao Paulo Research Foundation (FAPESP), Sao Paulo, Brazil [00669-9] FX The study received financial support from The State of Sao Paulo Research Foundation (FAPESP, project 00669-9), Sao Paulo, Brazil. NR 32 TC 11 Z9 12 U1 0 U2 6 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2009 VL 64 IS 7 BP 629 EP 635 DI 10.1590/S1807-59322009000700004 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 480HZ UT WOS:000268725900004 PM 19606237 ER PT J AU Nelson, AA Tsao, H AF Nelson, Andrew A. Tsao, Hensin TI Melanoma and genetics SO CLINICS IN DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; GERMLINE MUTATIONS; TUMOR SUPPRESSION; CDKN2A MUTATIONS; RED HAIR; INK4A; RISK; MC1R; PREVALENCE; VARIANTS AB As the incidence of malignant melanoma continues to increase and with the completion of the sequencing of the human genome, there have been increasing efforts to identify the "melanoma gene (s)." Although some patients and families have significantly increased risks due to genetic predisposition, most melanoma cases are sporadic and likely result from low to moderate risk genetic factors. This review focuses on the genes that cover the greatest risk of developing melanoma. It is important to remember that many-if not most-cases of melanoma are the result of undiscovered variants. The strongest genetic risk for the development of melanoma results from heritable alterations in cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, which encodes two separate but related proteins, p16/(INK4a) and p14/(ARF). These proteins help regulate cell division and apoptosis, both of which are necessary to maintain cellular homeostasis. Other important genes include CDK4/6 and retinoblastoma (RBI), which encode downstream proteins in the same pathway as p16/(INK4a) and p14/(ARF). Finally, we discuss the relative importance of the melanocortin I receptor (MCIR) gene as a moderate risk factor for melanoma. Although great advances have been made in understanding the molecular basis and genetic predisposition of melanoma, many questions still remain to be answered. Someday soon, it will be possible to predict a patient's risk of melanoma by DNA analysis, however, it is important to reconcile our tremendous technologic capabilities with documented clinical utility. (C) 2009 Elsevier Inc. All rights reserved. C1 [Nelson, Andrew A.; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Melanoma & Pigmented Les Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. EM htsao@partners.org FU American Cancer Society FX Dr Tsao is supported in part by a agrant from the American Cancer Society and by donations to the Massachusetts General Hospital. NR 27 TC 30 Z9 31 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JAN-FEB PY 2009 VL 27 IS 1 BP 46 EP 52 DI 10.1016/j.clindermatol.2008.09.005 PG 7 WC Dermatology SC Dermatology GA 397RW UT WOS:000262680800006 PM 19095153 ER PT J AU Spencer, TJ Arnsten, AFT Scahill, L Wigal, SB AF Spencer, Thomas J. Arnsten, Amy F. T. Scahill, Lawrence Wigal, Sharon B. TI Advances in Attention-Deficit Hyperactivity Disorder Treatment A Focus on the Role of Noradrenergic and Alpha-2a Receptor Modulation SO CNS DRUGS LA English DT Editorial Material C1 [Spencer, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program, Boston, MA 02115 USA. [Arnsten, Amy F. T.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Scahill, Lawrence] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Scahill, Lawrence] Yale Univ, Sch Nursing, New Haven, CT 06520 USA. [Wigal, Sharon B.] Univ Calif Irvine, Irvine, CA USA. [Wigal, Sharon B.] Child Dev Ctr, Irvine, CA USA. RP Spencer, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2009 VL 23 BP 1 EP 4 PG 4 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 478WT UT WOS:000268620000001 ER PT J AU Spencer, TJ AF Spencer, Thomas J. TI Toward a New Understanding of Attention-Deficit Hyperactivity Disorder Advances in Research and Treatment INTRODUCTION SO CNS DRUGS LA English DT Editorial Material ID DEFICIT/HYPERACTIVITY DISORDER; COMORBID ANXIETY; CHILDREN; ADHD; GUANFACINE; CLONIDINE; ATOMOXETINE; ASSOCIATION; ADOLESCENTS; SYMPTOMS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin & Res Program, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin & Res Program, 55 Fruit St Warren 705, Boston, MA 02114 USA. NR 34 TC 3 Z9 3 U1 2 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2009 VL 23 BP 5 EP 8 PG 4 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 478WT UT WOS:000268620000002 PM 19621973 ER PT J AU Spencer, TJ AF Spencer, Thomas J. TI Issues in the Management of Patients with Complex Attention-Deficit Hyperactivity Disorder Symptoms SO CNS DRUGS LA English DT Review ID OPPOSITIONAL DEFIANT DISORDER; SUBSTANCE USE DISORDERS; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIALS; PEDIATRIC BIPOLAR DISORDER; MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; MIXED AMPHETAMINE SALTS; OPEN-LABEL TRIAL; DEFICIT/HYPERACTIVITY-DISORDER AB Patients with attention-deficit hyperactivity disorder (ADHD) exhibit a wide range of symptoms related to functional impairment. Psychiatric comorbidities are highly prevalent among these patients, often emerging at an early age and persisting (or reoccurring) into adulthood. Among the most coinmon types of coniorbidities in children and adults are disruptive behaviour disorders such as oppositional defiant disorder and conduct disorder, mood disorders, anxiety disorders, and substance use disorders. The heterogeneous clinical presentation of ADH D, which also changes with maturation into adulthood, may often obscure the presence of psychiatric comorbidity. Co-occurring disorders frequently go undetected and lead to negative effects on psychosocial and long-term functional outcomes. As with uncomplicated ADHD, medication therapy combined with psychosocial interventions may be necessary. With cornorbid disorders, two or more inedications may be considered to appropriately manage both ADHD and the comorbid disorder. However, there are few studies that discuss combination medication treatments and there are no current US FDA-approved combined treatments for ADHD and comorbid conditions. This raises significant challenges and risks for poor tolerability and drug-drug interactions. Nevertheless, identification and appropriate treatment must be given a high priority for these highly vulnerable patients to derive optimal benefits from treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program, 55 Fruit St Warren 705, Boston, MA 02114 USA. NR 100 TC 9 Z9 9 U1 2 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2009 VL 23 BP 9 EP 20 PG 12 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 478WT UT WOS:000268620000003 PM 19621974 ER PT J AU Rush, AJ Warden, D Wisniewski, SR Fava, M Trivedi, MH Gaynes, BN Nierenberg, AA AF Rush, A. John Warden, Diane Wisniewski, Stephen R. Fava, Maurizio Trivedi, Madhukar H. Gaynes, Bradley N. Nierenberg, Andrew A. TI STAR*D Revising Conventional Wisdom SO CNS DRUGS LA English DT Article ID MAJOR DEPRESSIVE DISORDER; SEQUENCED TREATMENT ALTERNATIVES; MEASUREMENT-BASED CARE; QUALITY-OF-LIFE; DIAGNOSTIC SCREENING QUESTIONNAIRE; MEDICATION ALGORITHM PROJECT; D CLINICAL-TRIAL; REPORT QIDS-SR; RELIEVE DEPRESSION; ANTIDEPRESSANT TREATMENT AB The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequenced, randomized treatment trials following a first and, if needed, subsequent treatment steps to define the tolerability and effectiveness of various options in both acute and longer term treatment. Adult outpatients (n=4041) with nonpsychotic major depressive disorder, substantial chronic and recurrent depression, and co-morbid psychiatric and general medical conditions were enrolled in 41 representative primary and specialty care settings. About one-third of participants remitted in first step treatment with citalopram, 50% of these within 6 weeks. Poorer outcomes were associated with minority status, socioeconomic disadvantage, more axis I and III co-morbid disorders, lower function and quality of life, and anxious and melancholic features. In step 2 medication switch, there were no significant differences in remission among within-class, out-of-class or dual-action agents: sertraline (27%), bupropion-sustained release (26%) and venlafaxine-extended release (25%). In step 2 medication augmentation of citalopram, there was no significant difference in remission between bupropion-sustained release (39%) and buspirone (33%), although participants using bupropion-sustained release had greater symptom reduction and better tolerability. There were no significant differences in remission in step 2 between cognitive therapy and medication treatment in either the switch (31% vs 27%) or augmentation (31% vs 33%) strategies, although participants in cognitive therapy augmentation had a longer time to remission than those in medication augmentation (55 vs 40 days). In step 3, there were no differences in remission between a switch to mirtazapine (8%) or nortriptyline (12%), or between augmentation with lithium (13%) or T3 (triiodothyronine, liothyronine) [25%], although more participants discontinued lithium due to adverse effects than discontinued T(3). In the fourth step, there was no difference in remission between tranylcypromine (14%) or venlafaxine-extended release plus mirtazapine (16%), although the combination treatment had fewer adverse effects and had the advantages of not requiring a washout period or diet restrictions. Participants requiring more than two well delivered treatments may be characterized as treatment resistant given the substantially lower remission rates after that point. Treatment resistance was associated with more concurrent axis I or III co-morbid conditions, socioeconomic disadvantage, chronicity and melancholic or anxious features. However, if participants remained in treatment for up to four steps, about 67% reached remission. Times to remission were not substantially longer for later treatment steps. The importance of reaching remission is highlighted by the lower relapse rates in naturalistic follow-up for participants entering in remission compared with those entering with response but not remission (step 1: 34% vs 59%; step 2: 47% vs 68%; step 3: 42% vs 76%; step 4: 50% vs 83%). Clinical decision making based on the itemized measurement of symptoms and adverse effects at each treatment visit was feasible in STAR*D's real world settings and resulted in adequate dosages and durations of treatment that generally exceeded those typically found in practice settings. Although switch and augmentation strategies could not be directly compared due to the equipoise stratified randomized design, the higher remission rates at step 2 with medication augmentation are intriguing and merit further study. C1 [Rush, A. John] Duke Natl Univ Singapore, Grad Sch Med, Dept Clin Sci, Singapore 169547, Singapore. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Rush, A. John; Warden, Diane; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Fava, Maurizio; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Gaynes, Bradley N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. RP Rush, AJ (reprint author), Duke Natl Univ Singapore, Grad Sch Med, Dept Clin Sci, 2 Jalan Bukit Merah, Singapore 169547, Singapore. EM john.rush@duke-nus.sg OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH900034] NR 93 TC 102 Z9 103 U1 3 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2009 VL 23 IS 8 BP 627 EP 647 PG 21 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 477UU UT WOS:000268545200001 PM 19594193 ER PT J AU Bhuvaneswar, CG Baldessarini, RJ Harsh, VL Alpert, JE AF Bhuvaneswar, Chaya G. Baldessarini, Ross J. Harsh, Veronica L. Alpert, Jonathan E. TI Adverse Endocrine and Metabolic Effects of Psychotropic Drugs Selective Clinical Review SO CNS DRUGS LA English DT Review ID INDUCED WEIGHT-GAIN; PLACEBO-CONTROLLED TRIAL; NEPHROGENIC DIABETES-INSIPIDUS; ANTIPSYCHOTIC-INDUCED HYPERPROLACTINEMIA; TREATMENT-RESISTANT SCHIZOPHRENIA; SEROTONIN REUPTAKE INHIBITORS; POLYCYSTIC OVARIAN SYNDROME; INDUCED SEXUAL DYSFUNCTION; BONE-MINERAL DENSITY; BIPOLAR-I DISORDER AB The article critically reviews selected, clinically significant, adverse endocrine and metabolic effects associated with psychotropic drug treatments, including hyperprolactinaemia, hyponatraemia, diabetes insipidus, hypothyroidism, hyperparathyroidism, sexual dysfunction and virilization, weight loss, weight gain and metabolic syndrome (type 2 diabetes mellitus, dyslipidaemia and hypertension). Such effects are prevalent and complex, but can be managed clinically when recognized. They encourage continued critical assessment of benefits versus risks of psychotropic drugs and underscore the importance of close coordination of psychiatric and general medical care to improve long-term health of psychiatric patients. Options for management of hyperprolactinaemia include lowering doses, switching to agents such as aripiprazole, clozapine or quetiapine, managing associated osteoporosis, carefully considering the use of dopamine receptor agonists; and ruling out stress, oral contraceptive use and hypothyroidism as contributing factors. Disorders of water homeostasis may include syndrome of inappropriate antidiuretic hormone (SIADH), managed by water restriction or slow replacement by hypertonic saline along with drug discontinuation. Safe management of diabetes insipidus, commonly associated with lithium, involves switching mood stabilizer and consideration of potassium-sparing diuretics. Clinical hypothyroidism may be a more useful marker than absolute cut-offs of hormone values, and may be associated with quetiapine, antidepressant and lithium use, and managed by thyroxine replacement. Hyper-parathyroidism requires comprehensive medical evaluation for occult tumours. Hypocalcaemia, along with multiple other psychiatric and medical causes, may result in decreased bone density and require evaluation and management. Strategies for reducing sexual dysfunction with psychotropics remain largely unsatisfactory. Finally, management strategies for obesity and metabolic syndrome are reviewed in light of the recent expert guidelines, including risk assessment and treatments, such as monoamine transport inhibitors, anticonvulsants; and cannabinoid receptor antagonists, as well as lifestyle changes. C1 [Bhuvaneswar, Chaya G.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Baldessarini, Ross J.; Alpert, Jonathan E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.; Alpert, Jonathan E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baldessarini, Ross J.] McLean Hosp, Belmont, MA 02178 USA. [Harsh, Veronica L.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Bhuvaneswar, CG (reprint author), Univ Penn, Hosp Univ Penn, Outpatient Clin, Dept Psychiat, 3535 Market St,2nd Floor, Philadelphia, PA 19104 USA. EM cbhospitalpsychiatry@live.com OI Alpert, Jonathan/0000-0002-4332-908X FU American Psychiatric Institute for Research and Education (APIRE); NIMH Diversity Supplement; Bruce J. Anderson Foundation; McLean Private Donors Fund FX Dr Bhuvaneswar has received training awards from: Merck, Janssen, Johnson and Johnson, Novartis, Sepracor, Cypress Bio and Infiniti Pharmaceuticals. Dr Baldessarini has recently been a consultant or investigator-initiated research collaborator with: Auritec, Biotrofix, IFA SpA, Janssen, JDS, Lilly, NeuroHealing, Novartis, Solvay and SK-BioPharmaceuticals Corporations. Dr Harsh has no relevant disclosures. Dr Alpert is a consultant or has received research support from: Aspect Medical Systems, Lilly, Forest, Organon, Pamlab, Pfizer and Pharmavite, and honoraria from Organon and Janssen Corportions. No author is a member of pharmaceutical speakers' bureaus nor do they or family members hold equity positions in biomedical or pharmaceutical corporations. NR 248 TC 27 Z9 27 U1 5 U2 19 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2009 VL 23 IS 12 BP 1003 EP 1021 PG 19 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 538EV UT WOS:000273168000002 PM 19958039 ER PT J AU Simon, NM Kaufman, RE Hoge, EA Worthington, JJ Herlands, NN Owens, ME Pollack, MH AF Simon, Naomi M. Kaufman, Rebecca E. Hoge, Elizabeth A. Worthington, John J. Herlands, Nannette N. Owens, Maryann E. Pollack, Mark H. TI Open-Label Support for Duloxetine for the Treatment of Panic Disorder SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Anxiety; antidepressant; duloxetine; panic; pharmacotherapy; treatment ID VENLAFAXINE; PAROXETINE; SEROTONIN; EFFICACY; SCALE AB Panic disorder with or without agoraphobia is a common, often chronic and refractory anxiety disorder. Although a number of pharmacotherapies are now indicated for panic disorder, many patients do not respond to available interventions. We hypothesized that duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI) that has greater initial noradrenergic effects than venlafaxine, would have broad efficacy for individuals with panic disorder. Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day. Duloxetine treatment resulted in significant anxiolysis as measured by the primary outcome measure, the Panic Disorder Severity Scale (PDSS) (paired t(df) = 4.02(14), P = 0.0013), as well as measures of generalized anxiety, depression and quality of life (all P < 0.05). Although definitive conclusions are limited due to its small open-label nature, this first prospective study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger randomized controlled study is warranted. C1 [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org RI Hoge, Elizabeth/H-5879-2012; OI Hoge, Elizabeth/0000-0002-5513-2292; Sripada, Rebecca/0000-0002-2844-3458 NR 15 TC 17 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 1 BP 19 EP 23 DI 10.1111/j.1755-5949.2008.00076.x PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 407GX UT WOS:000263352700003 PM 19228176 ER PT J AU Marques, L Kaufman, RE LeBeau, RT Moshier, SJ Otto, MW Pollack, MH Simon, NM AF Marques, Luana Kaufman, Rebecca E. LeBeau, Richard T. Moshier, Samantha J. Otto, Michael W. Pollack, Mark H. Simon, Naomi M. TI A Comparison of Emotional Approach Coping (EAC) between Individuals with Anxiety Disorders and Nonanxious Controls SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Anxiety; Anxiety sensitivity; Coping; Emotional regulation; Panic; Phobia ID PANIC DISORDER; SENSITIVITY; DYSREGULATION; ADJUSTMENT; STRATEGIES; VALIDATION; PREDICTOR; SYMPTOMS; ATTACKS; HEALTH AB Emotional regulation deficits are described as a core component of anxiety disorders (ADs), yet there remains a paucity of data examining this issue in patients diagnosed with ADs. We hypothesized that help-seeking individuals with ADs would report lower levels of emotional approach coping (EAC), which includes emotional processing (EP) and emotional expression (EE), than nonanxious controls. Diagnostic interviews and a validated self-report scale assessing emotional approaches to coping (emotional approach coping scale [EACS]) were administered to 101 nonanxious controls and 92 patients with a primary AD (29 generalized anxiety disorder, 40 social anxiety disorder, and 23 panic disorder). Patients with each AD demonstrated significantly lower EAC, including both EP and EE, than nonanxious controls. Lower EAC was also associated with higher anxiety sensitivity and higher anxiety symptom severity. Overall, gender did not moderate the anxiety-EAC effect, but the results suggested that women utilize EAC to a greater degree than men. Clinical techniques designed to improve emotional coping may be beneficial to individuals with ADs. C1 [Marques, Luana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Otto, Michael W.] Boston Univ, Boston, MA 02215 USA. RP Marques, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM lmarques@partners.org OI Sripada, Rebecca/0000-0002-2844-3458 FU Highland Street Foundation FX This research was supported in part by a grant from the Highland Street Foundation. NR 36 TC 2 Z9 2 U1 2 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 2 BP 100 EP 106 DI 10.1111/j.1755-5949.2009.00080.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 443AW UT WOS:000265883600002 PM 19492991 ER PT J AU Hinton, DE Pollack, MH AF Hinton, Devon E. Pollack, Mark H. TI Introduction to the Special Issue: Anxiety Disorders in Cross-Cultural Perspective SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Editorial Material DE Anxiety disorders; Catastrophic cognitions; Cognitive theory; Cross-cultural AB This special issue explores the cross-cultural variation in the presentation and generation of anxiety disorders. As a background review, in this Introduction, we illustrate how the cognitive theory of the generation of anxiety disorders explains how such cross-cultural variation occurs. We first show how the "catastrophic cognitions" theory applies to panic disorder and then suggest how the "catastrophic cognitions" theory applies to all anxiety disorders-and so explains the existence of profound cultural influence on the presentation and generation of the anxiety disorders. C1 [Hinton, Devon E.; Pollack, Mark H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hinton, Devon E.; Pollack, Mark H.] Harvard Univ, Sch Med, Boston, MA USA. [Hinton, Devon E.] Arbour Counseling Ctr, SE Asian Clin, Lowell, MA USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 2 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 3 BP 207 EP 209 DI 10.1111/j.1755-5949.2009.00097.x PG 3 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 481ER UT WOS:000268790700001 PM 19691539 ER PT J AU Paradis, C Friedman, S Hinton, DE McNally, RJ Solomon, LZ Lyons, KA AF Paradis, Cheryl Friedman, Steven Hinton, Devon E. McNally, Richard J. Solomon, Linda Z. Lyons, Kelly A. TI The Assessment of the Phenomenology of Sleep Paralysis: The Unusual Sleep Experiences Questionnaire (USEQ) SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Isolated sleep paralysis; Sleep disturbance; Sleep paralysis ID MEDICAL-STUDENTS; COLLEGE-STUDENTS; PREVALENCE; HALLUCINATIONS; FREQUENCY; DIAGNOSIS AB Previous research has found a relationship between sleep paralysis (SP) and anxiety states and higher rates have been reported among certain ethnic groups. To advance the cross-cultural study of SP, we developed a brief assessment instrument (which can be self-administered), the Unusual Sleep Experiences Questionnaire (USEQ). In this article, we report on a pilot study with the USEQ in a sample of 208 college students. The instrument was easily understood by the participants, with one quarter reporting at least one lifetime episode of SP. As in previous studies, SP was associated with anxiety (in particular, panic attacks). C1 [Paradis, Cheryl] Marymt Manhattan Coll, Pratt Stn, Brooklyn, NY 11205 USA. [Paradis, Cheryl; Friedman, Steven] Suny Downstate Med Ctr, Dept Psychiat, Brooklyn, NY 11203 USA. [Hinton, Devon E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hinton, Devon E.] SE Asian Clin, Boston, MA USA. RP Paradis, C (reprint author), Marymt Manhattan Coll, Pratt Stn, POB 050-145, Brooklyn, NY 11205 USA. EM cparadis@mmm.edu NR 30 TC 5 Z9 5 U1 2 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 3 BP 220 EP 226 DI 10.1111/j.1755-5949.2009.00098.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 481ER UT WOS:000268790700003 PM 19691541 ER PT J AU Asnaani, A Gutner, CA Hinton, DE Hofmann, SG AF Asnaani, Anu Gutner, Cassidy A. Hinton, Devon E. Hofmann, Stefan G. TI Panic Disorder, Panic Attacks and Panic Attack Symptoms across Race-Ethnic Groups: Results of the Collaborative Psychiatric Epidemiology Studies SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Anxiety; Cross-cultural; Epidemiology; Panic attacks; Panic disorder ID NATIONAL-COMORBIDITY-SURVEY; ASIAN-AMERICAN; UNITED-STATES; LATINO; RELIABILITY; PREVALENCE; VALIDITY; SERVICES; ANXIETY AB The current study investigates race-ethnic differences in rates of panic disorder, panic attacks and certain panic attack symptoms by jointly combining three major national epidemiological databases. The compared groups were White, African American, Latino and Asian. The White group had significantly higher rates of panic disorder, and of many panic symptoms, including palpitations, as compared to the African American, Asian and Latino groups. Several expected race-ethnic differences were not found. An explanation for these findings are adduced, and suggestions are given for future studies so that possible ethnic-racial differences in panic disorder, panic attacks and panic attack symptoms can be investigated in a more rigorous manner. C1 [Asnaani, Anu; Gutner, Cassidy A.; Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Hinton, Devon E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Fl, Boston, MA 02215 USA. EM shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 FU NIMH [1R01MH078308, R01MH079032] FX Dr. Hofmann is a paid consultant by Schering-Plough and supported by NIMH grant 1R01MH078308. Dr. Hinton is supported by NIMH grant R01MH079032. NR 15 TC 13 Z9 13 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 3 BP 249 EP 254 DI 10.1111/j.1755-5949.2009.00092.x PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 481ER UT WOS:000268790700006 PM 19691544 ER PT J AU Hinton, DE Hofmann, SG Pollack, MH Otto, MW AF Hinton, Devon E. Hofmann, Stefan G. Pollack, Mark H. Otto, Michael W. TI Mechanisms of Efficacy of CBT for Cambodian Refugees with PTSD: Improvement in Emotion Regulation and Orthostatic Blood Pressure Response SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Cambodian refugees; Cognitive-behavior therapy; Emotion regulation; Orthostatic intolerance; Panic attacks; Posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIOR THERAPY; TREATMENT-RESISTANT PTSD; PANIC DISORDER; HEART-RATE; SCALE; SEVERITY; ATTACKS; DYSREGULATION; DIFFICULTIES AB Based on the results of a randomized controlled trial, we examined a model of the mechanisms of efficacy of culturally adapted cognitive-behavior therapy (CBT) for Cambodian refugees with pharmacology-resistant posttraumatic stress disorder (PTSD) and comordid orthostatic panic attacks (PAs). Twelve patients were in the initial treatment condition, 12 in the delayed treatment condition. The patients randomized to CBT had much greater improvement than patients in the waitlist condition on all psychometric measures and on one physiological measure-the systolic blood pressure response to orthostasis (d = 1.31)-as evaluated by repeated-measures MANOVA and planned contrasts. After receiving CBT, the Delayed Treatment Group improved on all measures, including the systolic blood pressure response to orthostasis. The CBT treatment's reduction of PTSD severity was significantly mediated by improvement in orthostatic panic and emotion regulation ability. The current study supports our model of the generation of PTSD in the Cambodian population, and suggests a key role of decreased vagal tone in the generation of orthostatic panic and PTSD in this population. It also suggests that vagal tone is involved in emotion regulation, and that both vagal tone and emotion regulation improve across treatment. C1 [Hinton, Devon E.; Pollack, Mark H.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hinton, Devon E.] SE Asian Clin, Lowell, MA USA. [Hofmann, Stefan G.; Otto, Michael W.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Hinton, DE (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02115 USA. EM devon_hinton@hms.harvard.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 32 TC 47 Z9 49 U1 1 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 3 BP 255 EP 263 DI 10.1111/j.1755-5949.2009.00100.x PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 481ER UT WOS:000268790700007 PM 19691545 ER PT J AU Hinton, DE Lewis-Fernandez, R Pollack, MH AF Hinton, Devon E. Lewis-Fernandez, Roberto Pollack, Mark H. TI A Model of the Generation of Ataque de Nervios: The Role of Fear of Negative Affect and Fear of Arousal Symptoms SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Anxiety; Anxiety sensitivity; Ataque de nervios; Cultural syndromes; Idioms of distress ID ANXIETY SENSITIVITY; PANIC-ATTACKS; CAMBODIAN REFUGEES; DISORDER; DISSOCIATION; PREDICTION; COMMUNITY; AMERICANS AB This article examines a model of the generation of ataque de nervios, according to which both fear of negative affectivity and fear of arousal symptoms are associated with the emergence of ataques. We examine the relationship of fear of negative affectivity and fear of arousal to the severity of ataque de nervios during the last month and the last 6 months among Caribbean Latinos residing in the United States. The measures include a Fear of Anger Scale and the Anxiety Sensitivity Index (ASI), the ASI augmented with two items that assess fear of arousal symptoms common in ataques: chest tightness and a sense of inner heat. In keeping with the model of ataque generation, one-way analysis of variances (ANOVAs) and discriminant function analyses illustrated that items assessing "fear of negative affect" and "fear of somatic and psychological symptoms of arousal" both differentiated well among the levels of ataque severity. In addition, key ataque symptoms-mental incapacitation fears, shakiness, chest tightness, palpitations, and a sense of inner heat-were the best discriminators among levels of ataque severity. In patients with severe ataques, the scores of "fear of negative affect" and "fear of ataque-de-nervios-type somatic and psychological symptoms" were extremely elevated. This further suggests that both these types of fears are associated with this idiom of distress and that the specific content of the fears is linked to the symptom picture of the idiom. This suggests specific therapeutic targets for the treatment of ataque, namely, the reduction of anxiety sensitivity (and more generally negative-emotion and arousal sensitivity) using cognitive behavioral therapy (CBT), relaxation, and mindfulness techniques. C1 [Hinton, Devon E.; Pollack, Mark H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hinton, Devon E.; Pollack, Mark H.] Harvard Univ, Sch Med, Boston, MA USA. [Hinton, Devon E.] Arbour Counseling Ctr, SE Asian Clin, Lowell, MA USA. [Lewis-Fernandez, Roberto] Columbia Univ, New York, NY USA. [Lewis-Fernandez, Roberto] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 24 TC 20 Z9 20 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 3 BP 264 EP 275 DI 10.1111/j.1755-5949.2009.00101.x PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 481ER UT WOS:000268790700008 PM 19691546 ER PT J AU Li, Y Marques, L Hinton, DE Wang, Y Xiao, ZP AF Li, Ying Marques, Luana Hinton, Devon E. Wang, Yuan Xiao, Ze-Ping TI Symptom Dimensions in Chinese Patients with Obsessive-Compulsive Disorder SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Chinese patients; DY-BOCS; Obsessive-compulsive disorder (OCD); Symptom dimension ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; DSM-IV; PERSONALITY-DISORDER; CLINICAL-FEATURES; SCALE; PHENOMENOLOGY; EPIDEMIOLOGY; CHECKERS; SUBTYPES; WASHERS AB To study the symptom dimensions of Chinese patients with obsessive-compulsive disorder (OCD), the symptom checklist of the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) was used to assess the symptom dimensions of 139 OCD patients at a mental health center in Shanghai. The most common symptom dimensions were symmetry (67.6%), contamination (43.2%), and aggression (31.7%). The frequency of patients with the miscellaneous, sexual/religious, and hoarding symptom dimensions was 25.9%, 10.8%, and 8.6%, respectively. The frequency of male patients with symmetry concerns was higher than that of the female patients, and the frequency of female patients with contamination concerns was higher than that of male patients. OCD symptom dimensions can be identified in the Chinese context but there is a low frequency of endorsement of certain dimensions: sexual/religious, aggression, and hoarding concerns. Future studies need to further investigate the sociocultural and gender factors that may result in these findings: low numbers of people in China with a religious affiliation and the Chinese emphasis on Confucian harmony philosophy, thrift, and saving. C1 [Li, Ying; Wang, Yuan; Xiao, Ze-Ping] Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China. [Marques, Luana; Hinton, Devon E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Xiao, ZP (reprint author), Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, 600 Wan Ping Nan Rd, Shanghai 200030, Peoples R China. EM xiaozeping@gmail.com FU New Frontier Technology in Shanghai municipal hospitals [SHDC12006105]; National High Technology Research and Development Program of China [2007AA02Z420]; Science and Technology Commission of Shanghai municipality [074119520]; Program for Shanghai Outstanding Academic Leader Plans [08XD14036] FX This study was supported by a joint key project of New Frontier Technology in Shanghai municipal hospitals (No: SHDC12006105), the National High Technology Research and Development Program of China (No: 2007AA02Z420), a key project from Science and Technology Commission of Shanghai municipality (No: 074119520), and the Program for Shanghai Outstanding Academic Leader Plans (No: 08XD14036). The authors would like to thank Prof. Mary-Jo Delvecchio Good and Prof. Byron J. Good, Harvard University, for their assistance. NR 30 TC 14 Z9 15 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 3 BP 276 EP 282 DI 10.1111/j.1755-5949.2009.00099.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 481ER UT WOS:000268790700009 PM 19691547 ER PT J AU Hinton, DE Park, L Hsia, C Hofmann, S Pollack, MH AF Hinton, Devon E. Park, Lawrence Hsia, Curtis Hofmann, Stefan Pollack, Mark H. TI Anxiety Disorder Presentations in Asian Populations: A Review SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Anxiety disorders; Asian; Catastrophic cognitions; Functional somatic syndromes; Panic attacks ID TRAUMATIZED CAMBODIAN REFUGEES; COGNITIVE-BEHAVIOR THERAPY; TREATMENT-RESISTANT PTSD; FOCUSED PANIC-ATTACKS; ORTHOSTATIC DYSREGULATION; TAIJIN-KYOFUSHO; HWA-BYUNG; SYMPTOM PRESENTATION; VIETNAMESE REFUGEES; JAPANESE AB This article reviews typical anxiety presentations in Asia, and among Asian refugees. In Asia, there are multiple functional somatic syndromes that are common anxiety presentations. These distress syndromes often produce catastrophic cognitions about anxiety-type somatic and psychological symptoms. These functional somatic syndromes should be understood, and specifically assessed and addressed, in order to optimize the evaluation and treatment of anxiety disorders among Asian individuals. C1 [Hinton, Devon E.; Park, Lawrence; Pollack, Mark H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Hinton, Devon E.] Arbour Counseling Ctr, Lowell, MA USA. [Hofmann, Stefan] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Hsia, Curtis] Azusa Pacific Univ, Dept Psychol, Azusa, CA USA. RP Hinton, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 60 TC 17 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 3 BP 295 EP 303 DI 10.1111/j.1755-5949.2009.00095.x PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 481ER UT WOS:000268790700011 PM 19691549 ER PT J AU Iosifescu, DV Moore, CM Deckersbach, T Tilley, CA Ostacher, MJ Sachs, GS Nierenberg, AA AF Iosifescu, Dan V. Moore, Constance M. Deckersbach, Thilo Tilley, Claire A. Ostacher, Michael J. Sachs, Gary S. Nierenberg, Andrew A. TI Galantamine-ER For Cognitive Dysfunction In Bipolar Disorder and Correlation with Hippocampal Neuronal Viability: A Proof-of-Concept Study SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Acetylcholinesterase inhibitors; Bipolar disorder; Cognitive dysfunction; Galantamine; Magnetic resonance spectroscopy ID MAGNETIC-RESONANCE-SPECTROSCOPY; ANTERIOR CINGULATE CORTEX; OXYGEN-GLUCOSE DEPRIVATION; EUTHYMIC PATIENTS; FUNCTIONAL IMPAIRMENT; I DISORDER; NEUROPSYCHOLOGICAL DYSFUNCTION; UNIPOLAR DEPRESSION; ALZHEIMERS-DISEASE; N-ACETYLASPARTATE AB Method: Nineteen subjects with bipolar disorder in remission, who reported subjective cognitive deficits, were treated with open-label galantamine-ER 8-24 mg/day for 4 months. Ten healthy volunteers matched for age and gender were also assessed. Mood and subjective cognitive questionnaires were administered monthly. At the beginning and the end of the trial all subjects were administered neuropsychological tests, including tests of attention (Conners CPT) and episodic memory (CVLT). Bipolar subjects underwent proton magnetic resonance spectroscopy (1H-MRS) measurements before and after treatment, healthy volunteers completed baseline 1H-MRS. We acquired 1H-MRS data at 4.0 T from voxels centered on the left and right hippocampus to measure hippocampal N-acetyl aspartate (NAA, a measure of neuronal viability) and choline containing compounds (Cho, a marker of lipid metabolism and membrane turn-over). Results: Compared to healthy volunteers, bipolar subjects had higher baseline subjective cognitive deficits and lower scores on objective tests of attention (Conner's CPT) and verbal episodic memory (CVLT). After treatment, bipolar subjects experienced significant improvement of subjective cognitive scores and on objective tests of attention (Conner's CPT) and verbal episodic memory (CVLT). In the left hippocampus NAA increased and choline (Cho) decreased in bipolar subjects during treatment. Conclusion: Bipolar subjects had cognitive dysfunction; treatment with Galantamine-ER was associated with improved cognition and with increases in neuronal viability and normalization of lipid membrane metabolism in the left hippocampus. This study was registered on ClinicalTrials.gov (NCT00181636). C1 [Iosifescu, Dan V.; Deckersbach, Thilo; Tilley, Claire A.; Ostacher, Michael J.; Sachs, Gary S.; Nierenberg, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Moore, Constance M.] Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Boston, MA 02114 USA. RP Iosifescu, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU Ortho-McNeil Neurologics, Inc FX This study was supported by a grant from Ortho-McNeil Neurologics, Inc (Dr. Iosifescu). NR 67 TC 21 Z9 23 U1 2 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 4 BP 309 EP 319 DI 10.1111/j.1755-5949.2009.00090.x PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 516BS UT WOS:000271517300003 PM 19889129 ER PT J AU Kashner, TM Trivedi, MH Wicker, A Fava, M Wisniewski, SR Rush, AJ AF Kashner, T. Michael Trivedi, Madhukar H. Wicker, Annie Fava, Maurizio Wisniewski, Stephen R. Rush, A. John TI The Impact of Nonclinical Factors on Care Use for Patients with Depression: A STAR*D Report SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Cost of care; Disease management system; Healthcare utilization; Program evaluation; Severe mental illness ID SEQUENCED TREATMENT ALTERNATIVES; MENTAL-HEALTH-CARE; MEDICATION ALGORITHM PROJECT; REPORT QIDS-SR; SELF-REPORT; PREDICTING COSTS; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; REGRESSION-MODELS; MAJOR DEPRESSION AB Introduction: This article presents baseline findings that describe how nonclinical factors were associated with patient use of psychiatric and general medical care and how those relationships changed after patients enrolled in the 41-site Sequenced Treatment Alternatives to Relieve Depression study (STAR*D). Aims: STAR*D offered adult outpatients with major depression diligently delivered, measurement-based care. To achieve full remission within a tolerable medication dose, recommendations for treatment based on routine symptom and side-effect measurements were discussed with patients by clinical research coordinators and offered to clinicians who could flexibly tailor that guidance to accommodate individual patient needs. Medications were provided gratis. Pre- and post-enrollment data came from provider records and from patient face-to-face, telephone, and computer-assisted surveys. Two-part nested mixed models assessed patient likelihood and volume of mental and general medical care services. Results: Prior to enrollment, predisposing (gender, race, education, and care attitude), affordability (private insurance), and clinical factors (depressive symptoms and mental and physical functioning) were found to be important drivers of patient use of psychiatric and general medical care. After STAR*D enrollment, however, predisposing factors were less important drivers of psychiatric service use but remained important drivers of general medical care. Conclusions: Data suggest diligent, measurement-based mental health programs may reduce race, gender, and education disparities in the use of needed mental health care. C1 [Kashner, T. Michael; Trivedi, Madhukar H.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Kashner, T. Michael] Off Acad Affiliat, Vet Hlth Adm, Dept Vet Affairs, Washington, DC USA. [Wicker, Annie] N Texas Hlth Care Syst, Dept Vet Affairs, Dallas, TX USA. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. [Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. RP Kashner, TM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM michael.kashner@va.gov OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health, National Institutes of Health [N01-MH-90003] FX This project has been funded in whole or in part with federal funds from the National Institute of Mental Health, National Institutes of Health, under contract N01-MH-90003 (A.J. Rush MD, P.I.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services or the Department of Veterans Affairs, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 68 TC 7 Z9 7 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2009 VL 15 IS 4 BP 320 EP 332 DI 10.1111/j.1755-5949.2009.00091.x PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 516BS UT WOS:000271517300004 PM 19712127 ER PT J AU Cruciani, M Lipsky, BA Mengoli, C de Lalla, F AF Cruciani, M. Lipsky, B. A. Mengoli, C. de Lalla, F. TI Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot infections SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID MONONUCLEAR-CELL IMPLANTATION; CRITICAL LIMB ISCHEMIA; MEDICAL-TREATMENT; CONTROLLED-TRIAL; AUTOLOGOUS TRANSPLANTATION; LOCAL CARE; ULCERS; IMPROVES; FILGRASTIM; METAANALYSIS AB Background G-CSF increases the release of neutrophil endothelial progenitor cells from the bone marrow, and improves neutrophil functions, which are often impaired in people with diabetes. Objectives To examine the effects of adjunctive G-CSF compared with placebo or no growth factor added to usual care on rates of infection, cure and wound healing in people with diabetes who have a foot infection. Search strategy We searched the Cochrane Wounds Group Specialised Register (Searched 16/3/09); the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 1 2009); Ovid MEDLINE (1950 to March Week 1 2009); Ovid EMBASE (1980 to 2009 Week 11); EBSCO CINAHL (1982 to March Week 2 2009); LookSmart's Find Articles (January 1990 to January 2008); conference proceedings and references lists in the included studies. Selection criteria Randomised controlled trials (RCTs) that evaluated the effect of adding G-CSF to usual care in people with a diabetic foot infection. Data collection and analysis Three review authors independently assessed trial eligibility, methodological quality and extracted data. Relative risk (RR), or for continuous outcomes, mean differences (MD), with 95% confidence intervals (CI) were reported. In the case of low or no heterogeneity studies were pooled using a fixed-effect model. Main results We identified and included five eligible trials with a total of 167 patients. The investigators administered various G-CSF preparations, at different doses and for different durations of time. Adding G-CSF did not significantly affect the likelihood of resolution of infection or wound healing, but it was associated with a significantly reduced likelihood of lower extremity surgical interventions (RR 0.37; 95 % CI 0.20 to 0.68), including amputation (RR 0.41; 95 % CI 0.18 to 0.95). Moreover, providing G-CSF reduced the duration of hospital stay ( MD, -1.40 days; 95% CI, -2.27 to -0.53 days), but did not significantly affect the duration of systemic antibiotic therapy (MD, -0.27 days; 95 % CI, -1.30 to 0.77 days). Authors' conclusions The available evidence is limited, but suggests that adjunctive G-CSF treatment in people with a diabetic foot infection, including infected ulcers, does not appear to increase the likelihood of resolution of infection or healing of the foot ulcer. However, it does appear to reduce the need for surgical interventions, especially amputations, and the duration of hospitalisation. Clinicians might consider adding G-CSF to the usual treatment of diabetic foot infections, especially in patients with a limb-threatening infection, but it is not clear which patients might benefit. C1 [Cruciani, M.] G Fracastoro Hosp, Ctr Prevent Med, I-37135 Verona, Italy. [Cruciani, M.] G Fracastoro Hosp, HIV Outpatient Clin, I-37135 Verona, Italy. [Lipsky, B. A.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Mengoli, C.] Univ Padua, Dept Histol Microbiol & Med Biotechnol, Padua, Italy. [de Lalla, F.] Osped san Bortolo, Dept Infect Dis, Vicenza, Italy. RP Cruciani, M (reprint author), G Fracastoro Hosp, Ctr Prevent Med, Via Germania 20, I-37135 Verona, Italy. EM crucianimario@virgilio.it OI Lipsky, Benjamin A./0000-0001-9886-5114; Mengoli, Carlo/0000-0002-7422-0554 NR 66 TC 16 Z9 16 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2009 IS 3 AR CD006810 DI 10.1002/14651858.CD006810.pub2 PG 35 WC Medicine, General & Internal SC General & Internal Medicine GA 471EE UT WOS:000268037500012 PM 19588405 ER PT J AU O'Connor, AM Bennett, CL Stacey, D Barry, M Col, NF Eden, KB Entwistle, VA Fiset, V Holmes-Rovner, M Khangura, S Llewellyn-Thomas, H Rovner, D AF O'Connor, A. M. Bennett, C. L. Stacey, D. Barry, M. Col, N. F. Eden, K. B. Entwistle, V. A. Fiset, V Holmes-Rovner, M. Khangura, S. Llewellyn-Thomas, H. Rovner, D. TI Decision aids for people facing health treatment or screening decisions SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; BREAST-CANCER SUSCEPTIBILITY; DIAGNOSED HYPERTENSIVE PATIENTS; PATIENT-PHYSICIAN PARTNERSHIP; BENIGN PROSTATIC HYPERPLASIA; EVIDENCE-BASED INFORMATION; INTERACTIVE VIDEO PROGRAM; CELL LUNG-CANCER; INFORMED-CONSENT AB Background Decision aids prepare people to participate in 'close call' decisions that involve weighing benefits, harms, and scientific uncertainty. Objectives To conduct a systematic review of randomised controlled trials (RCTs) evaluating the efficacy of decision aids for people facing difficult treatment or screening decisions. Search strategy We searched MEDLINE (Ovid) (1966 to July 2006); Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library; 2006, Issue 2); CINAHL (Ovid) (1982 to July 2006); EMBASE (Ovid) (1980 to July 2006); and PsycINFO (Ovid) (1806 to July 2006). We contacted researchers active in the field up to December 2006. There were no language restrictions. Selection criteria We included published RCTs of interventions designed to aid patients' decision making by providing information about treatment or screening options and their associated outcomes, compared to no intervention, usual care, and alternate interventions. We excluded studies in which participants were not making an active treatment or screening decision, or if the study's intervention was not available to determine that it met the minimum criteria to qualify as a patient decision aid. Data collection and analysis Two review authors independently screened abstracts for inclusion, and extracted data from included studies using standardized forms. The primary outcomes focused on the effectiveness criteria of the International Patient Decision Aid Standards (IPDAS) Collaboration: attributes of the decision and attributes of the decision process. We considered other behavioural, health, and health system effects as secondary outcomes. We pooled results of RCTs using mean differences (MD) and relative risks (RR) using a random effects model. Main results This update added 25 new RCTs, bringing the total to 55. Thirty-eight (69%) used at least one measure that mapped onto an IPDAS effectiveness criterion: decision attributes: knowledge scores (27 trials); accurate risk perceptions (11 trials); and value congruence with chosen option (4 trials); and decision process attributes: feeling informed (15 trials) and feeling clear about values (13 trials). This review confirmed the following findings from the previous (2003) review. Decision aids performed better than usual care interventions in terms of: a) greater knowledge (MD 15.2 out of 100; 95% CI 11.7 to 18.7); b) lower decisional conflict related to feeling uninformed (MD -8.3 of 100; 95% CI -11.9 to -4.8); c) lower decisional conflict related to feeling unclear about personal values (MD -6.4; 95% CI -10.0 to -2.7); d) reduced the proportion of people who were passive in decision making (RR 0.6; 95% CI 0.5 to 0.8); and e) reduced proportion of people who remained undecided post-intervention (RR 0.5; 95% CI 0.3 to 0.8). When simpler decision aids were compared to more detailed decision aids, the relative improvement was significant in knowledge (MD 4.6 out of 100; 95% CI 3.0 to 6.2) and there was some evidence of greater agreement between values and choice. In this review, we were able to explore the use of probabilities in decision aids. Exposure to a decision aid with probabilities resulted in a higher proportion of people with accurate risk perceptions (RR 1.6; 95% CI 1.4 to 1.9). The effect was stronger when probabilities were measured quantitatively (RR 1.8; 95% CI 1.4 to 2.3) versus qualitatively (RR 1.3; 95% CI 1.1 to 1.5). As in the previous review, exposure to decision aids continued to demonstrate reduced rates of: elective invasive surgery in favour of conservative options, decision aid versus usual care (RR 0.8; 95% CI 0.6 to 0.9); and use of menopausal hormones, detailed versus simple aid (RR 0.7; 95% CI 0.6 to 1.0). There is now evidence that exposure to decision aids results in reduced PSA screening, decision aid versus usual care (RR 0.8; 95% CI 0.7 to 1.0). For other decisions, the effect on decisions remains variable. As in the previous review, decision aids are no better than comparisons in affecting satisfaction with decision making, anxiety, and health outcomes. The effects of decision aids on other outcomes (patient-practitioner communication, consultation length, continuance, resource use) were inconclusive. There were no trials evaluating the IPDAS decision process criteria relating to helping patients to recognize a decision needs to be made, understand that values affect the decision, or discuss values with the practitioner. Authors' conclusions Patient decision aids increase people's involvement and are more likely to lead to informed values-based decisions; however, the size of the effect varies across studies. Decision aids have a variable effect on decisions. They reduce the use of discretionary surgery without apparent adverse effects on health outcomes or satisfaction. The degree of detail patient decision aids require for positive effects on decision quality should be explored. The effects on continuance with chosen option, patient-practitioner communication, consultation length, and cost-effectiveness need further evaluation. C1 [O'Connor, A. M.] Univ Ottawa, Dept Epidemiol, Sch Nursing, Ottawa, ON K1Y 4E9, Canada. [O'Connor, A. M.; Bennett, C. L.; Khangura, S.] Ottawa Hlth Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Barry, M.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Col, N. F.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04102 USA. [Eden, K. B.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR USA. [Entwistle, V. A.] Univ Dundee, Social Dimens Hlth Inst, Dundee, Scotland. [Fiset, V] Algonquin Coll, Nursing Program, Ottawa, ON, Canada. [Holmes-Rovner, M.] Michigan State Univ, Coll Human Med, Ctr Eth & Humanities Life Sci, E Lansing, MI 48824 USA. [Llewellyn-Thomas, H.] Dartmouth Coll, Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH USA. RP O'Connor, AM (reprint author), Univ Ottawa, Dept Epidemiol, Sch Nursing, 1053 Carling Ave,ASB 2-008, Ottawa, ON K1Y 4E9, Canada. EM aoconnor@ohri.ca OI Entwistle, Vikki/0000-0002-0856-4025 FU Agency for Healthcare Research and Quality, USA [HHSA29030050013C]; Canadian Institutes of Health Research, Canada [MGC 42668] FX Agency for Healtlicare Research and Quality, USA.; KB is currently directing patient decision aid development for the John M. Eisenberg Clinical Decisions and Communications Science Center funded by the Agency for Heaithcare Research and Quality (HHSA29020050013C) and located at Oregon Health & Science University in Portland, Oregon.; Canadian Institutes of Health Research, Canada.; Group Grant in Decision Support Tools for Clinicians and Patients (MGC 42668) provided salary (CB, SK) and material (systematic review software) support.; Canada Research Chair Program, Canada.; AO holds a Tier 1 Canada Research Chair in Health Care Consumer Decision Support. NR 183 TC 312 Z9 315 U1 5 U2 39 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2009 IS 3 AR CD001431 DI 10.1002/14651858.CD001431.pub2 PG 119 WC Medicine, General & Internal SC General & Internal Medicine GA 471EH UT WOS:000268037800014 PM 19588325 ER PT J AU Barrett, LF AF Barrett, Lisa Feldman TI Variety is the spice of life: A psychological construction approach to understanding variability in emotion SO COGNITION & EMOTION LA English DT Review DE Affect; Categorization; Construction; Perception ID INDIVIDUAL-DIFFERENCES; NUCLEUS-ACCUMBENS; CATEGORICAL PERCEPTION; FACIAL EXPRESSIONS; MORAL JUDGMENT/; WORKING-MEMORY; VALENCE FOCUS; AROUSAL FOCUS; FEELING GOOD; CORE AFFECT AB There is remarkable variety in emotional life. Not all mental states referred to by the same word (e.g., ofearo) look alike, feel alike, or have the same neurophysiological signature. Variability has been observed within individuals over time, across individuals from the same culture, and of course across cultures. In this paper, I outline an approach to understanding the richness and diversity of emotional life. This model, called the conceptual act model, is not only well suited to explaining individual differences in the frequency and quality of emotion, but it also suggests the counter-intuitive view that the variety in emotional life extends past the boundaries of events that are conventionally called oemotiono to other classes of psychological events that people call by different names, such as ocognitionso. As a result, the conceptual act model is a unifying account of the broad variety of mental states that constitute the human mind. C1 [Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. EM barretli@bc.edu FU NIA NIH HHS [R01 AG030311-04, R01 AG030311]; NIH HHS [DP1 OD003312, DP1 OD003312-03] NR 132 TC 79 Z9 80 U1 1 U2 25 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PY 2009 VL 23 IS 7 BP 1284 EP 1306 AR PII 912825248 DI 10.1080/02699930902985894 PG 23 WC Psychology, Experimental SC Psychology GA 500GU UT WOS:000270287600003 PM 20221411 ER PT J AU Zaitchik, D Solomon, GEA AF Zaitchik, Deborah Solomon, Gregg E. A. TI Conservation of species, volume, and belief in patients with Alzheimer's disease: The issue of domain specificity and conceptual impairment SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article DE Alzheimer's disease; Ageing; Cognitive development; Intuitive biology; Domain specificity; Conceptual impairment; Piagetian conservation ID SEMANTIC MEMORY IMPAIRMENT; ANIMATE-INANIMATE DISTINCTION; CATEGORY-SPECIFIC DEFICITS; LIVING THINGS; MULTIPLE SEMANTICS; FALSE BELIEF; NONLIVING THINGS; KNOWLEDGE; DISSOCIATIONS; DEMENTIA AB Two studies investigated whether patients with Alzheimer's disease (AD) suffer high-level and category-specific impairment in the conceptual domain of living things. In Experiment 1, AD patients and healthy young and healthy elderly controls took part in three tasks: the conservation of species, volume, and belief. All 3 tasks required tracking an object's identity in the face of irrelevant but salient transformations. Healthy young and elderly controls performed at or near ceiling on all tasks. AD patients were at or near ceiling on the volume and belief tasks, but only about half succeeded on the species task. Experiment 2 demonstrated that the results were not due to simple task demands. AD patients' failure to conserve species indicates that they are impaired in their theoretical understanding of living things, and their success on the volume and belief tasks suggests that the impairment is domain-specific. Two hypotheses are put forward to explain the phenomenon: The first, a category-specific account, holds that the intuitive theory of biology undergoes pervasive degradation; the second, a hybrid domain-general/domain-specific account, holds that impairment to domain-general processes such as executive function interacts with core cognition, the primitive elements that are the foundation of domain-specific knowledge. C1 [Zaitchik, Deborah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Solomon, Gregg E. A.] Natl Sci Fdn, Div Res Learning, Arlington, VA 22230 USA. RP Zaitchik, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM dzaitchiksamet@partners.org FU National Institutes of Health [NIH/NIA AG020548]; National Science Foundation FX We thank Marilyn Albert, Lynelle Cortellini, Rebecca England, Kathryn Fitzpatrick, Sarah Helmstadter, Jerry Samet, Yaakov Stern, Caren Walker, and the Hebrew Rehabilitation Center for the Aged. The first author was supported by a grant from the National Institutes of Health (NIH/NIA AG020548), and the second author was supported by the IR/D program of the National Science Foundation. NR 81 TC 6 Z9 6 U1 3 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PY 2009 VL 26 IS 6 BP 511 EP 526 DI 10.1080/02643290903478549 PG 16 WC Psychology; Psychology, Experimental SC Psychology GA 564EE UT WOS:000275195300002 PM 20043252 ER PT J AU Yang, JY Chinchilli, VM AF Yang, Jingyun Chinchilli, Vernon M. TI Fixed-Effects Modeling of Cohen's Kappa for Bivariate Multinomial Data SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Agreement; Categorical data; Kappa; Largest eigenvalue ID CONCORDANCE CORRELATION-COEFFICIENT; NOMINAL SCALE AGREEMENT; MULTIPLE RATERS; WEIGHTED KAPPA; RELIABILITY; REPRODUCIBILITY AB Cohen's kappa statistic is the conventional method that is used widely in measuring agreement between two responses when they are categorical. In this article, we develop a fixed-effects modeling of Cohen's kappa for bivariate multinomial data which reduces to Cohen's kappa under certain conditions and hence can be considered as a generalization of the conventional Cohen's kappa. Also, this method can easily be adapted as a generalization of Cohen's weighted kappa. Properties of the proposed method are provided. Large sample performance is investigated through bootstrap simulation studies followed by two illustrative examples. C1 [Yang, Jingyun] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Chinchilli, Vernon M.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA. RP Yang, JY (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM jingyuny@gmail.com NR 33 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2009 VL 38 IS 20 BP 3634 EP 3653 AR PII 915802176 DI 10.1080/03610920802618426 PG 20 WC Statistics & Probability SC Mathematics GA 506VY UT WOS:000270806000002 ER PT J AU Kogai, T Brent, GA AF Kogai, Takahiko Brent, Gregory A. BE Preedy, VR Burrow, GN Watson, RR TI Regulation and Enhancement of Endogenous Sodium Iodide Symporter Expression: NIS Regulatory Pathways in Thyroid and Breast Cancer SO COMPREHENSIVE HANDBOOK OF IODINE: NUTRITIONAL, BIOCHEMICAL, PATHOLOGICAL AND THERAPEUTIC ASPECTS LA English DT Article; Book Chapter ID HUMAN CHORIONIC-GONADOTROPIN; CHORIOCARCINOMA CELL-LINE; SODIUM/IODIDE SYMPORTER; GENE-EXPRESSION; NA+/I-SYMPORTER; RADIOIODIDE UPTAKE; TRANSCRIPTION FACTOR; DIFFERENTIAL REGULATION; UPSTREAM ENHANCER; CARCINOMA CELLS AB The sodium iodide symporter (NIS) gene is expressed at a high level in the thyroid gland and the lactating breast. Thyroid-stimulating hormone, or thyrotropin (TSH) is the major regulator of NIS expression in the normal thyroid and also stimulates NIS in more than 80% of differentiated thyroid cancers. TSH stimulates NIS gene expression through the proximal promoter and the NIS far upstream enhancer (NUE). The NUE requires at least two transcription factors, Pax-8 and CREB, for stimulation. Reduced expression of these transcription factors may contribute to the reduction in NIS expression that is seen in some differentiated thyroid cancer. High levels of endogenous TSH, or administration of recombinant TSH, are required to enhance the iodide uptake in thyroid cancer before radioiodide therapy. NIS gene expression in lactating breast tissue is primarily regulated by oxytocin and prolactin. A modest level of NIS expression has been reported in approximately 80% of cases of breast cancers. A number of strategies have been used to enhance NIS expression and radioiodide uptake in thyroid cancer and breast cancer. These include redifferentiation agents, such as retinoic acid and other nuclear hormone receptor ligands, as well as epigenetic modifiers. The results from application of these agents to in vitro models of thyroid and breast cancer will be described. Insights into NIS regulation, as well as agents that promote endogenous NIS expression, should lead to new approaches to using radioiodine in the treatment of thyroid and breast cancers. C1 [Kogai, Takahiko; Brent, Gregory A.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med, David Geffen Sch Med,Mol Endocrinol Lab, Los Angeles, CA 90073 USA. [Kogai, Takahiko; Brent, Gregory A.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Physiol, David Geffen Sch Med,Mol Endocrinol Lab, Los Angeles, CA 90073 USA. RP Kogai, T (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med, David Geffen Sch Med,Mol Endocrinol Lab, Los Angeles, CA 90073 USA. NR 46 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-092086-3 PY 2009 BP 221 EP 230 DI 10.1016/B978-0-12-374135-6.00023-6 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Nutrition & Dietetics GA BCR55 UT WOS:000311104900024 ER PT B AU Rehman, SU Ahmed, MM Hutchison, FN AF Rehman, Shakaib U. Ahmed, Mohammed M. Hutchison, Florence N. BE Preedy, VR Burrow, GN Watson, RR TI Goiter in the Elderly: The Role of Iodine SO COMPREHENSIVE HANDBOOK OF IODINE: NUTRITIONAL, BIOCHEMICAL, PATHOLOGICAL AND THERAPEUTIC ASPECTS LA English DT Article; Book Chapter ID PERCUTANEOUS ETHANOL INJECTION; NODULAR THYROID-DISEASE; OPERATIVE MANAGEMENT; INTRATHORACIC GOITER; SURGICAL-MANAGEMENT; SUBSTERNAL GOITER; THERAPY; OBSTRUCTION; DISORDERS; HYPERTHYROIDISM AB The term goiter means thyroid enlargement, either diffuse or nodular. The incidence of goiter increases with age. The most common type of goiter in the elderly is multinodular goiter. Graves' disease is very rare in older adults. The most common cause of goiter worldwide is iodine deficiency. It is becoming less of a problem in developed countries, due to the addition of iodine to salt and bread. Goiter commonly presents as neck mass. Although most patients with goiter do not have any symptom other than neck swelling, occasionally patients complain of dysphagia, dysphonia, or pain. Many goiters do not cause any thyroidal hormonal abnormality (euthyroid status). Some can present with either excess thyroidal hormonal activity (hyperthyroidism) or deficiency of thyroid hormones (hypothyroidism). Proper work-up for elderly patients with goiter includes a thorough history, detailed clinical examination, thyroid hormone assays, e. g., TSH, T4, T3, and an ultrasound or CT scan. Most goiters are benign in nature and may not require tissue diagnosis. In some elderly patients, fine needle aspiration and biopsy may be considered to rule out malignancy. Most elderly patients with nodular goiter are treated best by surgical removal, while radioiodine therapy and/or antithyroid drugs are the most effective therapy for non-nodular goiter. C1 [Rehman, Shakaib U.; Hutchison, Florence N.] Ralph H Johnson Vet Affairs Hosp, Charleston, SC 29401 USA. [Rehman, Shakaib U.; Hutchison, Florence N.] Med Univ S Carolina, Charleston, SC 29401 USA. [Ahmed, Mohammed M.] Univ Toledo, Dept Med, Toledo, OH 43614 USA. RP Rehman, SU (reprint author), Ralph H Johnson Vet Affairs Hosp, Charleston, SC 29401 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-092086-3; 978-0-12-374135-6 PY 2009 BP 323 EP 329 DI 10.1016/B978-0-12-374135-6.00034-0 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Nutrition & Dietetics GA BCR55 UT WOS:000311104900035 ER PT J AU Flory, JD Yehuda, R Grossman, R New, AS Mitropoulou, V Siever, LJ AF Flory, Janine D. Yehuda, Rachel Grossman, Robert New, Antonia S. Mitropoulou, Vivian Siever, Larry J. TI Childhood trauma and basal cortisol in people with personality disorders SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ABUSE; NEGLECT; DEPRESSION; BEHAVIOR AB This study examined the influence of various forms of childhood abuse on basal cortisol levels in a sample of adults with Axis II personality disorders. Participants included 63 adults (n = 19 women) who provided basal plasma cortisol samples and completed the Childhood Trauma Questionnaire. Linear regression analyses that included all 5 subscales (ie, sexual abuse, physical abuse, emotional abuse, physical neglect and emotional neglect) demonstrated that physical abuse was related to lower cortisol levels (beta = -.43 P = .007), consistent with prior literature. In contrast, physical neglect was associated with higher cortisol (beta = .36, P = .02), after controlling for other forms of abuse. Results are consistent with the view that childhood trauma has long-lasting neurobiological effects and suggest that different forms of trauma may have distinct biological effects. (C) 2009 Elsevier Inc. All rights reserved. C1 [Flory, Janine D.] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Flory, Janine D.; Yehuda, Rachel; Grossman, Robert; New, Antonia S.; Mitropoulou, Vivian; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Yehuda, Rachel; New, Antonia S.; Siever, Larry J.] Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Flory, JD (reprint author), CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. EM janine.flory@qc.cuny.edu FU Mount Sinai General Clinical Research Center [MH069979, RO1 MH056606, RO1 MH063875, RO3 MH58697, MO1 RR0071] FX This work was supported by MH069979 (JDF) RO1 MH056606 (LJS), RO1 MH063875 (LJS), RO3 MH58697 (RG), and MO1 RR0071 (Mount Sinai General Clinical Research Center). NR 21 TC 24 Z9 24 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2009 VL 50 IS 1 BP 34 EP 37 DI 10.1016/j.comppsych.2008.05.007 PG 4 WC Psychiatry SC Psychiatry GA 389KA UT WOS:000262090100006 PM 19059511 ER PT J AU Mourdjeva, M Mandinova, A Kyurkchiev, S Kehayov, I AF Mourdjeva, Milena Mandinova, Anna Kyurkchiev, Stanimir Kehayov, Ivan TI EXPERIMENTAL DATA FOR INHIBITION OF THE EXPRESSION OF SURVIVIN BY SMALL INTERFERING RNA MOLECULES (siRNAs) SO COMPTES RENDUS DE L ACADEMIE BULGARE DES SCIENCES LA English DT Article DE survivin; siRNA; carcinoma cells AB This paper presents the data from experiments on: 1) isolation and purification of recombinant survivin with a view to use it for induction of polyclonal or monoclonal antibodies and, 2) inhibition of the synthesis and secretion of survivin in cell of PC-3 cell line isolated from prostate carcinoma. To these ends a plasmid containing cloned human survivin DNA was expressed in E. coli culture and after induction of its expression the recombinant protein was purified by affinity chromatography and characterized by immunoblot. The next step in our experiments was to check the possibility to inhibit the synthesis of survivin in PC-3 cells. In these experiments Signal Silence Survivin siRNA kit (Cell Signaling, USA) was used. The effect of the inhibition was followed by Western blot to detect changes in the survivin expression at protein level and real-time RT-PCR to assess the changes in the transcription of the specific mRNA. Both methods demonstrate that the introduction of survivin siRNA caused reduction of mRNA and protein expression in the treated PC-3 cells. C1 [Mourdjeva, Milena; Kyurkchiev, Stanimir; Kehayov, Ivan] Bulgarian Acad Sci, Inst Biol & Immunol Reprod, Acad K Bratanov, BU-1113 Sofia, Bulgaria. [Mandinova, Anna] Massachusetts Gen Hosp, Dept Dermatol, Charlstown, MA 02129 USA. RP Mourdjeva, M (reprint author), Bulgarian Acad Sci, Inst Biol & Immunol Reprod, Acad K Bratanov, 73 Tsarigradsko Chaussee Blvd, BU-1113 Sofia, Bulgaria. EM kehayoviv@yahoo.com OI Mourdjeva, Milena/0000-0003-1416-1457 FU Bulgarian Ministry of Education and Science [TKB-1609/06] FX This work was partly supported by a grant TKB-1609/06 from the National Science Fund at the Bulgarian Ministry of Education and Science. NR 5 TC 0 Z9 0 U1 0 U2 0 PU PUBL HOUSE BULGARIAN ACAD SCI PI SOFIA PA ACADEMICIAN G BONCEV ST, 1113 SOFIA, BULGARIA SN 1310-1331 J9 CR ACAD BULG SCI JI C. R. Acad. Bulg. Sci. PY 2009 VL 62 IS 5 BP 647 EP 650 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 469CL UT WOS:000267872800017 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Transposed Markov matrix as a new decision tool of how to choose among competing investment options in academic medicine SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article DE decision analysis; decision tree; Markov chain; stochastic modelling AB Medical institutions face the challenge of promoting excellence in a variety of competing focus areas, such as grants, publications, income, research, faculty, variety, patient care and teaching. A transposed Markov chain is used analyse the interactions between the various focus areas and their transition towards steady-state. In contradistinction with a regular Markov chain, in the transposed chain used for the present analysis, the sum of inputs (rather than outputs) of each individual state is 100%, whereas the outputs are left to assume any possible value. The mathematics of calculating the steady state conditions of a transposed Markov matrix are similar to those of a regular Markov matrix. The analysis shows that a focus area more dependent on other areas is also more likely to lose its investment, whereas largely self-reliant areas will generate the largest return. Full strength of all academic focus areas can be achieved only by investments in all areas. In academic systems with one or several exclusively self-reliant focus areas, only investment in these particular areas will invigorate the system, as all other investments are bound to dissipate over time. The newly developed decision tool of a transposed Markov matrix could be helpful in stochastic modelling of medical phenomena. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Portland, OR USA. EM sonnenbe@ohsu.edu NR 11 TC 2 Z9 2 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2009 VL 10 IS 1 BP 1 EP 7 AR PII 789782974 DI 10.1080/17486700701865323 PG 7 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 428LD UT WOS:000264848500001 ER PT B AU Cheng, JT Ravicz, ME Rosowski, JJ Hulli, N Hernandez-Montes, MS Furlong, C AF Cheng, Jeffrey T. Ravicz, Michael E. Rosowski, John J. Hulli, Nesim Hernandez-Montes, Maria S. Furlong, Cosme BE Cooper, NP Kemp, DT TI TIME AVERAGE HOLOGRAPHY STUDY OF HUMAN TYMPANIC MEMBRANE WITH ALTERED MIDDLE EAR OSSICULAR CHAIN SO CONCEPTS AND CHALLENGES IN THE BIOPHYSICS OF HEARING LA English DT Proceedings Paper CT 10th International Workshop on the Mechanics of Hearing CY JUL 27-31, 2008 CL Keele Univ, Staffordshire, ENGLAND SP Oticon Fdn, Otodynam Ltd, Starkey Lab Ltd, MED EL, Polytec GmbH, Tucker Davis Technol HO Keele Univ AB Computer-assisted time average holographic interferometry was used to study the vibration of the human tympanic membrane (TM) in cadaveric temporal bones before and after alterations of the ossicular chain. Simultaneous laser Doppler vibrometer measurements of stapes velocity were performed to estimate the conductive hearing loss caused by ossicular alterations. The quantified TM motion described from holographic images was correlated with stapes velocity to define relations between TM motion and stapes velocity in various ossicular disorders. The results suggest that motions of the TM are relatively uncoupled from stapes motion at frequencies above 1000 Hz. C1 [Cheng, Jeffrey T.; Ravicz, Michael E.; Rosowski, John J.] Harvard Univ, Sch Med, EPL, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cheng, JT (reprint author), Harvard Univ, Sch Med, EPL, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-283-377-8 PY 2009 BP 3 EP 8 DI 10.1142/9789812833785_0001 PG 6 WC Biophysics SC Biophysics GA BKL64 UT WOS:000268443600001 ER PT B AU Guinan, JJ AF Guinan, J. J., Jr. BE Cooper, NP Kemp, DT TI BIAS-TONE EFFECTS ON THE FIRST-PEAK VERSUS LATER PEAKS OF AUDITORY-NERVE RESPONSES SO CONCEPTS AND CHALLENGES IN THE BIOPHYSICS OF HEARING LA English DT Proceedings Paper CT 10th International Workshop on the Mechanics of Hearing CY JUL 27-31, 2008 CL Keele Univ, Staffordshire, ENGLAND SP Oticon Fdn, Otodynam Ltd, Starkey Lab Ltd, MED EL, Polytec GmbH, Tucker Davis Technol HO Keele Univ ID INNER HAIR CELL; BASILAR-MEMBRANE; FIBER RESPONSES; COCHLEA; SUPPRESSION; MODULATION; CLICKS; LEVEL; CORTI AB Preliminary experiments show that low-frequency "bias" tones at sound levels that produce twice-a-cycle suppression of low-level, cochlear-amplified auditory-nerve (AN) responses, suppress the first peak of AN click responses in different ways depending on click level. At moderate click levels, the most common bias-tone effect was twice-a-cycle suppression, but at high click levels where the AN first peak switches from rarefaction to condensation clicks, bias tones sinusoidally modulated the click response. The results are consistent with the hypothesis that AN first-peak responses to high-level clicks originate from a different cochlear vibrational mode than other AN responses. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-283-377-8 PY 2009 BP 155 EP 161 DI 10.1142/9789812833785_0024 PG 7 WC Biophysics SC Biophysics GA BKL64 UT WOS:000268443600024 ER PT S AU Helleso, R Eines, J Sorensen, L Fagermoen, MS AF Helleso, Ragnhild Eines, Johannes Sorensen, Lena Fagermoen, May Solveig BE Saranto, K Brennan, PF Park, HA Tallberg, M Ensio, A TI Severity of Illness - Implications for Information Management by Patients SO CONNECTING HEALTH AND HUMANS SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 10th International Congress on Nursing Informatics CY JUN 28-JUL 01, 2009 CL Helsinki, FINLAND SP Finnish Nurses Assoc DE Information management; information strategies; chronic heart insufficiency; discharge summary; electronic patient record ID HEART-FAILURE; CARE AB As more and More people are living with chronic diseases, there is a greater need for patients to have access to accurate and reliable information about health in general and their own health care in particular. In this Study we explored how patients suffering from chronic heart insufficiency who needed post-hospital home nursing care assessed their need for health information and their use of the health information they received. Fourteen patients were interviewed in their homes one week after their discharge. Using a thematic approach, we identified three main areas: the hospital systems for providing information to patients, how patients processed the information, and how patients managed the information. Next of kin had a significant role in information management for the patient. The patient's condition has implications for his or her ability to manage the information, and therefore it seems important to customize information according to the patient's level of comprehension. C1 [Helleso, Ragnhild; Fagermoen, May Solveig] Univ Oslo, Fac Med, Inst Nursing & Hlth Sci, N-0316 Oslo, Norway. [Eines, Johannes; Fagermoen, May Solveig] Oslo Univ Hosp, N-0450 Oslo, Norway. [Sorensen, Lena] Massachusetts Gen Hosp, Inst Hlth Profession, Boston, MA 02114 USA. EM ragnhild.helleso@medisin.uio.no NR 19 TC 2 Z9 2 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-024-7 J9 STUD HEALTH TECHNOL PY 2009 VL 146 BP 373 EP + DI 10.3233/978-1-60750-024-7-373 PG 2 WC Health Policy & Services; Nursing SC Health Care Sciences & Services; Nursing GA BMS75 UT WOS:000273498700067 PM 19592869 ER PT J AU Schalock, PC AF Schalock, Peter C. TI Allergic contact cermatitis to retapamulin ointment SO CONTACT DERMATITIS LA English DT Editorial Material DE adverse drug reaction; allergic contact dermatitis; patch test; topical antibiotics; topical drugs C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Schalock, PC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, BAR622,55 Fruit St, Boston, MA 02114 USA. EM schalock@gmail.com NR 5 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-1873 J9 CONTACT DERMATITIS JI Contact Dermatitis PY 2009 VL 61 IS 2 BP 126 EP 126 PG 1 WC Allergy; Dermatology SC Allergy; Dermatology GA 486FY UT WOS:000269182800012 PM 19706058 ER PT J AU Wilt, TJ Brawer, MK Barry, MJ Jones, KM Kwon, Y Gingrich, JR Aronson, WJ Nsouli, I Iyer, P Cartagena, R Snider, G Roehrborn, C Fox, S AF Wilt, Timothy J. Brawer, Michael K. Barry, Michael J. Jones, Karen M. Kwon, Young Gingrich, Jeffrey R. Aronson, William J. Nsouli, Imad Iyer, Padmini Cartagena, Ruben Snider, Glenn Roehrborn, Claus Fox, Steven TI The Prostate cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): Design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer SO Contemporary Clinical Trials LA English DT Article DE Prostate cancer; Randomized clinical trial; Radical prostatectomy; Watchful waiting ID PROTECT AB Background: Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy). external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. Methods: We describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia. Results: We screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 102 ng/ml). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade and tumor stage, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Scandinavian trial. Conclusions: PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinically localized prostate cancer. Published by Elsevier Inc. C1 [Wilt, Timothy J.] Minneapolis VA Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Brawer, Michael K.] URIDEA, Seattle, WA USA. [Barry, Michael J.] Massachusetts Gen Hosp, Med Practices Evaluat Center, Boston, MA 02114 USA. [Jones, Karen M.] Vet Affairs Cooperat Studies Program Coordinating, Perry Point, MD USA. [Kwon, Young] Hampton VA Med Ctr, Hampton, VA USA. [Gingrich, Jeffrey R.] Univ Pittsburgh, Dept Urol, Pittsburgh, PA 15260 USA. [Gingrich, Jeffrey R.] Univ Pittsburgh, VA Pittsburgh Hlth Care System, Pittsburgh, PA 15260 USA. [Aronson, William J.] VA Med Ctr, Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Nsouli, Imad] VA Med Ctr Syracuse, New York, NY USA. [Iyer, Padmini] VA Med Center, Long Beach, CA USA. [Cartagena, Ruben] VA Western New York Hlth Syst, Buffalo, NY USA. [Snider, Glenn] Louis A Johnson VA Med Ctr, Clarksburg, WV USA. [Roehrborn, Claus] Univ Texas Dallas, SW Med Ctr, Dept Urol, Dallas, TX USA. [Fox, Steven] Agcy Healthcare Res & Quality, Rockville, MD USA. RP Wilt, TJ (reprint author), Minneapolis VA Ctr Chron Dis Outcomes Res, 1 Vet Dr 111-0, Minneapolis, MN 55417 USA. EM tim.wilt@med.va.gov FU Department of Veterans Affairs Cooperative Studies Program; National Cancer Institute; Agency for Healthcare Research and Quality FX Funding provided by the Department of Veterans Affairs Cooperative Studies Program, the National Cancer Institute and the Agency for Healthcare Research and Quality. NR 17 TC 84 Z9 91 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2009 VL 30 IS 1 BP 81 EP 87 DI 10.1016/j.ccr.2008.08.002 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 396PO UT WOS:000262603800013 PM 18783735 ER PT J AU Bajwa, EK AF Bajwa, Ednan K. TI The genetics of acute lung injury: looking back and pointing the way forward SO CRITICAL CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; ASSOCIATION; THERAPY AB Individual genetic factors have long been suspected of playing a major role in susceptibility to acute lung injury and acute respiratory distress syndrome. Flores and colleagues evaluate the quality of published studies testing the relationships between variation in candidate genes and susceptibility to lung injury syndromes or worsened outcome in patients with these conditions. Their results demonstrate that while important advances have been made in this area, attention should be paid to improving the methodology of future studies in order to minimize the chances of publishing false-positive results. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Bajwa, EK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM ebajwa@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2009 VL 13 IS 1 AR 108 DI 10.1186/cc7132 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 421IC UT WOS:000264351600036 PM 19183434 ER PT J AU Lang, JD Matute-Bello, G AF Lang, John D. Matute-Bello, Gustavo TI Lymphocytes, apoptosis and sepsis: making the jump from mice to humans SO CRITICAL CARE LA English DT Editorial Material ID MONOCYTE DEACTIVATION; UNITED-STATES; DOUBLE-BLIND; PHASE-III; RECEPTOR; TRIAL; EPIDEMIOLOGY; DEATH AB Sepsis is an important clinical problem with a mortality rate of 20% to 30%. Lymphocyte apoptosis has been recognized as an important step in the pathogenesis of experimental sepsis, by inducing a state of 'immune paralysis' that renders the host vulnerable to invading pathogens. The importance of lymphocyte apoptosis in human disease is now confirmed by Weber and colleagues, who demonstrate extensive apoptosis in circulating lymphocytes from patients with severe sepsis. Weber and colleagues' data set the basis for further studies aimed at modulating lymphocyte apoptosis in sepsis. C1 [Matute-Bello, Gustavo] Univ Washington, Dept Med, Ctr Lung Biol, Div Pulm & Crit Care Med, Seattle, WA 98109 USA. [Lang, John D.] VA Puget Sound HealthCare Syst, Seattle, WA 98108 USA. [Lang, John D.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. RP Matute-Bello, G (reprint author), Univ Washington, Dept Med, Ctr Lung Biol, Div Pulm & Crit Care Med, Seattle, WA 98109 USA. NR 14 TC 26 Z9 32 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2009 VL 13 IS 1 AR 109 DI 10.1186/cc7144 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 421IC UT WOS:000264351600037 PM 19216722 ER PT J AU Li, LF Huang, CC Lin, HC Tsai, YH Quinn, DA Liao, SK AF Li, Li-Fu Huang, Chung-Chi Lin, Horng-Chyuan Tsai, Ying-Huang Quinn, Deborah A. Liao, Shuen-Kuei TI Unfractionated heparin and enoxaparin reduce high-stretch ventilation augmented lung injury: a prospective, controlled animal experiment SO CRITICAL CARE LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; INDUCED NEUTROPHIL INFILTRATION; INDUCED PULMONARY-FIBROSIS; FACTOR-KAPPA-B; MECHANICAL VENTILATION; PROTEIN-C; GENE; FIBRINOLYSIS; COAGULATION; KINASE AB Introduction Dysregulation of coagulation and local fibrinolysis found in patients with acute lung injury often results in the need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and suppression of fibrinolytic activity, but the mechanisms are unclear. We hypothesized that subcutaneous injections of unfractionated heparin and enoxaparin would decrease neutrophil infiltration, lung edema, and plasminogen-activator inhibitor-1 (PAI-1) production in mice exposed to high-tidal-volume ventilation. Methods Male C57BL/6 mice, weighing 20 to 25 g, were exposed to either high-tidal-volume (30 ml/kg) or low-tidal-volume (6 ml/kg) mechanical ventilation with room air for 1 to 5 hours after 200 IU/kg or 400 IU/kg unfractionated heparin and 4 mg/kg or 8 mg/kg enoxaparin administration. Nonventilated mice served as a control group. Evan blue dye, lung wet- to dry-weight ratio, histopathologic grading of epithelium, myeloperoxidase, and gene expression of PAI-1 were measured. The expression of PAI-1 was studied by immunohistochemistry. Results High-tidal-volume ventilation induced increased microvascular permeability, neutrophil influx, PAI-1 mRNA expression, production of PAI-1 protein, and positive staining of PAI-1 in epithelium in a dose-dependent manner. Lung injury induced by high-tidal-volume ventilation was attenuated with PAI-1-deficient mice and pharmacologic inhibition of PAI-1 activity by low-dose unfractionated heparin and enoxaparin. Conclusions We conclude that high-tidal-volume mechanical ventilation increased microvascular permeability, neutrophil influx, lung PAI-1 mRNA expression, production of active PAI-1. The deleterious effects were attenuated by low-dose unfractionated heparin or enoxaparin treatment. Understanding the protective mechanism of unfractionated heparin and enoxaparin related to the reduction of PAI-1 may afford further knowledge of the effects of mechanical forces in the lung and development of possible therapeutic strategies involved in acute lung injury. C1 [Liao, Shuen-Kuei] Chang Gung Univ, Grad Inst Clin Med Sci, Tao Yuan 333, Taiwan. [Li, Li-Fu; Huang, Chung-Chi; Lin, Horng-Chyuan; Tsai, Ying-Huang] Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Dept Med, Tao Yuan 333, Taiwan. [Li, Li-Fu; Huang, Chung-Chi; Lin, Horng-Chyuan; Tsai, Ying-Huang] Chang Gung Mem Hosp, Dept Resp Therapy, Tao Yuan 333, Taiwan. [Quinn, Deborah A.] Massachusetts Gen Hosp, Dept Med, Pulm Unit, Boston, MA 02114 USA. [Quinn, Deborah A.] Massachusetts Gen Hosp, Dept Med, Crit Care Unit, Boston, MA 02114 USA. [Quinn, Deborah A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Quinn, Deborah A.] Novartis Inst Biomed Res, Cambridge, MA 02140 USA. RP Liao, SK (reprint author), Chang Gung Univ, Grad Inst Clin Med Sci, 259 Wen Hwa 1st Rd, Tao Yuan 333, Taiwan. EM liaosk@mail.cgu.edu.tw FU Chang Gung Medical Research [CMRPG361412] FX Sources of Support: Chang Gung Medical Research Project CMRPG361412. We thank Tsung-Pin Yu for his help in the experiment. NR 34 TC 23 Z9 24 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2009 VL 13 IS 4 AR R108 DI 10.1186/cc7949 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA 525OL UT WOS:000272225600005 PM 19580651 ER PT J AU Owens, RL Harris, RS Malhotra, A AF Owens, Robert L. Harris, R. Scott Malhotra, Atul TI Is the way to man's heart (and lung) through the abdomen? SO CRITICAL CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; PRESSURE-VOLUME CURVE; INTRAABDOMINAL HYPERTENSION; TRANSPULMONARY PRESSURES; VENTILATION; ESOPHAGEAL; FAILURE AB Intra-abdominal hypertension is increasingly recognized to be both prevalent and clinically important in medical and surgical intensive care units. Intra-abdominal pressure (IAP) can impact organ function throughout the body, and it can also complicate standard measurements used in intensive care units. The article by Krebs and colleagues reports the effect of IAP on respiratory function, gas exchange and hemodynamic function. Their results show a relatively small effect of modestly elevated IAP on these variables in their patient population. However, their work raises several questions for clinicians and researchers regarding the pathophysiology and management of IAP. C1 [Owens, Robert L.; Malhotra, Atul] Brigham & Womens Hosp, Div Sleep Med, Sleep Disorders Res Program, Boston, MA 02115 USA. [Owens, Robert L.; Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Harris, R. Scott] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Harris, R. Scott] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Owens, RL (reprint author), Brigham & Womens Hosp, Div Sleep Med, Sleep Disorders Res Program, 221 Longwood Ave, Boston, MA 02115 USA. EM rowens@partners.org FU NHLBI NIH HHS [F32 HL097578] NR 17 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2009 VL 13 IS 6 AR 199 DI 10.1186/cc8136 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 556DF UT WOS:000274567900039 PM 19909491 ER PT J AU Palevsky, PM O'Connor, TZ Chertow, GM Crowley, ST Zhang, JH Kellum, JA AF Palevsky, Paul M. O'Connor, Theresa Z. Chertow, Glenn M. Crowley, Susan T. Zhang, Jane Hongyuan Kellum, John A. CA US Dept Vet Affairs Natl Inst Hlth TI Intensity of renal replacement therapy in acute kidney injury: perspective from within the Acute Renal Failure Trial Network Study SO CRITICAL CARE LA English DT Article ID CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS HEMOFILTRATION; INTERMITTENT HEMODIALYSIS; RANDOMIZED-TRIAL; DIALYSIS; SUPPORT; SURVIVAL AB Determination of the optimal dose of renal replacement therapy in critically ill patients with acute kidney injury has been controversial. Questions have recently been raised regarding the design and execution of the US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) Study, which demonstrated no improvement in 60-day all-cause mortality with more intensive management of renal replacement therapy. In the present article we present our rationale for these aspects of the design and conduct of the study, including our use of both intermittent and continuous modalities of renal support, our approach to initiation of study therapy and the volume management during study therapy. In addition, the article presents data on hypotension during therapy and recovery of kidney function in the perspective of other studies of renal support in acute kidney injury. Finally, we address the implications of the ATN Study results for clinical practice from the perspective of the study investigators. C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.; Kellum, John A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. [O'Connor, Theresa Z.; Crowley, Susan T.; Zhang, Jane Hongyuan] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Crowley, Susan T.] Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM Palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Department of Veterans Affairs Office of Research and Development; National Institute of Diabetes and Digestive and Kidney Diseases [Y1-DK-3508-01] FX Supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development and by the National Institute of Diabetes and Digestive and Kidney Diseases (interagency agreement Y1-DK-3508-01). NR 32 TC 22 Z9 25 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2009 VL 13 IS 4 AR 310 DI 10.1186/cc7901 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 525OL UT WOS:000272225600066 PM 19678919 ER PT J AU Renaud, B Labarere, J Coma, E Santin, A Hayon, J Gurgui, M Camus, N Roupie, E Hemery, F Herve, J Salloum, M Fine, MJ Brun-Buisson, C AF Renaud, Bertrand Labarere, Jose Coma, Eva Santin, Aline Hayon, Jan Gurgui, Merce Camus, Nicolas Roupie, Eric Hemery, Francois Herve, Jerome Salloum, Mirna Fine, Michael J. Brun-Buisson, Christian TI Risk stratification of early admission to the intensive care unit of patients with no major criteria of severe community-acquired pneumonia: development of an international prediction rule SO CRITICAL CARE LA English DT Article ID SYSTEMIC INFLAMMATORY RESPONSE; SURVIVING SEPSIS CAMPAIGN; SEPTIC SHOCK; CONTROLLED-TRIAL; DECISION RULES; GUIDELINES; MANAGEMENT; OUTCOMES; ADULTS; MULTICENTER AB Introduction To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3. Methods Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support). Results A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population. Conclusions The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions. C1 [Renaud, Bertrand; Santin, Aline; Camus, Nicolas; Herve, Jerome; Salloum, Mirna] Grp Hosp Henri Mondor Albert Chenevier, AP HP, Dept Emergency Med, F-94010 Creteil, France. [Labarere, Jose; Brun-Buisson, Christian] CHU Grenoble, Unite Evaluat Med, F-38043 Grenoble, France. [Coma, Eva] USAC, Inst Catala Oncol, Hosp Duran & Reynals, Serv Atencio Continuada, Barcelona 08907, Spain. [Hayon, Jan] Ctr Hosp Intercommunal Poissy St Germain, Dept Intens Care Med, F-78100 St Germain En Laye, France. [Gurgui, Merce] Hosp Santa Creu & Sant Pau, Dept Emergency Med, Barcelona, Spain. [Camus, Nicolas; Brun-Buisson, Christian] Univ Paris 12, Fac Med, F-94000 Creteil, France. [Roupie, Eric] CHU Caen, Dept Emergency Med, Hop Cote Nacre, F-14033 Caen, France. [Roupie, Eric] Univ Caen Basse Normandie, Fac Med, F-14032 Caen, France. [Hemery, Francois] Grp Hosp Henri Mondor Albert Chenevier, AP HP, Dept Informat Hosp, PMSI & Rech Clin, F-94010 Creteil, France. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Fine, Michael J.] Univ Pittsburgh, UPMC Montefiore Hosp, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Brun-Buisson, Christian] Grp Hosp Henri Mondor Albert Chenevier, AP HP, F-94010 Creteil, France. RP Renaud, B (reprint author), Grp Hosp Henri Mondor Albert Chenevier, AP HP, Dept Emergency Med, F-94010 Creteil, France. EM bertrand.renaud@hmn.aphp.fr RI Labarere, Jose/N-1688-2014; OI Labarere, Jose/0000-0001-7621-6586 FU "Direction de la Recherche Clinique d'Ile de France" [AOM 89-145] FX This study was funded by the "Direction de la Recherche Clinique d'Ile de France" as part of the "Programme Hospitalier de Recherche Clinique" (Grant N degrees AOM 89-145). NR 33 TC 47 Z9 48 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2009 VL 13 IS 2 AR R54 DI 10.1186/cc7781 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 453UN UT WOS:000266638500026 PM 19358736 ER PT J AU Roberts, RJ Barletta, JF Fong, JJ Schumaker, G Kuper, PJ Papadopoulos, S Yogaratnam, D Kendall, E Xamplas, R Gerlach, AT Szumita, PM Anger, KE Arpino, PA Voils, SA Grgurich, P Ruthazer, R Devlin, JW AF Roberts, Russel J. Barletta, Jeffrey F. Fong, Jeffrey J. Schumaker, Greg Kuper, Philip J. Papadopoulos, Stella Yogaratnam, Dinesh Kendall, Elise Xamplas, Renee Gerlach, Anthony T. Szumita, Paul M. Anger, Kevin E. Arpino, Paul A. Voils, Stacey A. Grgurich, Philip Ruthazer, Robin Devlin, John W. TI Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study SO CRITICAL CARE LA English DT Article ID FATAL MYOCARDIAL FAILURE; INTENSIVE-CARE-UNIT; METABOLIC-ACIDOSIS; LACTIC-ACIDOSIS; CARDIAC-SURGERY; PATIENT; RHABDOMYOLYSIS; ANESTHESIA; CHILDREN; DEATH AB Introduction While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol. Methods Critically ill adults from 11 academic medical centers administered an infusion of propofol for [>/=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS. Results Among 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>/=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar. Conclusions Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS. C1 [Devlin, John W.] Northeastern Univ, Sch Pharm, Boston, MA 02115 USA. [Roberts, Russel J.] Tufts Med Ctr, Dept Pharm, Boston, MA 02111 USA. [Barletta, Jeffrey F.] Spectrum Hlth, Dept Pharm, Grand Rapids, MI 49503 USA. [Fong, Jeffrey J.] Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, Worcester, MA 01608 USA. [Schumaker, Greg] Tufts Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02111 USA. [Kuper, Philip J.] Mayo Clin, Mayo Sch Hlth Sci, Coll Med, Dept Pharm, Rochester, MN 55905 USA. [Papadopoulos, Stella; Grgurich, Philip] Boston Med Ctr, Dept Pharm, Boston, MA 02118 USA. [Yogaratnam, Dinesh] Univ Massachusetts, Dept Pharm, Mem Med Ctr, Worcester, MA 01605 USA. [Kendall, Elise] Concord Reg Hosp, Dept Pharm, Concord, NH 03301 USA. [Xamplas, Renee] John H Stroger Jr Hosp Cook Cty, Dept Pharm Practice, Chicago, IL 60612 USA. [Gerlach, Anthony T.] Ohio State Univ, Med Ctr, Dept Pharm, Columbus, OH 43210 USA. [Gerlach, Anthony T.] Ohio State Univ, Med Ctr, Ctr Crit Care, Columbus, OH 43210 USA. [Szumita, Paul M.; Anger, Kevin E.] Brigham & Womens Hosp, Dept Pharm Serv, Boston, MA 02115 USA. [Arpino, Paul A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Voils, Stacey A.] Virginia Commonwealth Univ Hlth Syst, Dept Pharm, Richmond, VA 23298 USA. [Ruthazer, Robin] Tufts Med Ctr, Biostat Res Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. RP Devlin, JW (reprint author), Northeastern Univ, Sch Pharm, 360 Huntington Ave,Mugar 206, Boston, MA 02115 USA. EM j.devlin@neu.edu OI Barletta, Jeffrey/0000-0002-9054-8218 FU Hospira Pharmaceuticals FX The authors acknowledge the efforts of Robert Maclean, Pharm. D. and Keith Dunn, Pharm. D. towards this study. This study was funded by an unrestricted grant from Hospira Pharmaceuticals. None of the authors have conflicts of interest surrounding this study. NR 74 TC 61 Z9 62 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2009 VL 13 IS 5 AR R169 DI 10.1186/cc8145 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 525OO UT WOS:000272226000028 PM 19874582 ER PT J AU Erickson, SE Shlipak, MG Martin, GS Wheeler, AP Ancukiewicz, M Matthay, MA Eisner, MD AF Erickson, Sara E. Shlipak, Michael G. Martin, Greg S. Wheeler, Arthur P. Ancukiewicz, Marek Matthay, Michael A. Eisner, Mark D. CA Natl Heart Lung & Blood Inst TI Racial and ethnic disparities in mortality from acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; race; ethnicity; mortality; epidemiology ID RESPIRATORY-DISTRESS-SYNDROME; CHRONIC ALCOHOL-ABUSE; MYOCARDIAL-INFARCTION; SOCIOECONOMIC-STATUS; CONTROLLED-TRIAL; CARE; VENTILATION; MANAGEMENT; OUTCOMES; STATES AB Objective: Little is known about the influence of race and ethnicity on mortality from acute lung injury (ALI). We sought to determine whether black race or Hispanic ethnicity is independently associated with mortality among patients with ALI. Design: Retrospective cohort study of patients enrolled in the Acute Respiratory Distress Syndrome Network randomized controlled trials. Setting: Adult intensive care units participating in the Acute Respiratory Distress Syndrome Network trials. Patients: A total of 2362 mechanically ventilated patients (11715 white, 449 black, and 198 Hispanic) with ALI. Measurements and Main Results. The primary outcome was 60-day mortality. A secondary outcome was number of ventilator-free days. Crude mortality was 33% for both blacks and Hispanics compared with 27% for whites (p = 0.02). After adjusting for demographic and clinical covariates, the association between race/ethnicity and mortality persisted (odds ratio [OR] = 1.42; 95% confidence interval [CI] 1.10-1.84 for blacks; OR = 1.94; 95% Cl, 1.36-2.77 for Hispanics; OR = 1.00 for whites). After adjustment for severity of illness (Acute Physiology Score), black race was no longer significantly associated with mortality (OR = 1.25; 95% Cl, 0.95-1.66), whereas the association with Hispanic ethnicity persisted (OR = 2.00; 95% Cl, 1.37-2.90). Hispanics had significantly fewer ventilator-free days compared with whites after adjustment for demographic and clinical covariates (mean difference in days = -2.3; 95% Cl -3.90 to -0.70). Conclusions. Black and Hispanic patients with ALI have a significantly higher risk of death compared with white patients. This increased risk seemed to be mediated by increased severity of illness at presentation for blacks, but was unexplained among Hispanics. (Grit Care Med 2009; 37:1-6) C1 [Erickson, Sara E.; Martin, Greg S.] Emory Univ, Dept Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA 30322 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Matthay, Michael A.; Eisner, Mark D.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA. [Wheeler, Arthur P.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. [Ancukiewicz, Marek] Massachusetts Gen Hosp, ARDS Network Clin Coordinating Ctr, Boston, MA 02114 USA. RP Erickson, SE (reprint author), Emory Univ, Dept Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA 30322 USA. EM sara.erickson@gmail.com RI Martin, Greg/B-4085-2009 OI Martin, Greg/0000-0002-9684-7593 FU NHLBI [P50 HL74005, R01 HL51856, HR046059] FX Supported, in part, by NHLBI P50 HL74005 (to MAM, MDE), NHLBI R01 HL51856 (to MAM) and NHLBI HR046059 (ARDS Network). NR 25 TC 50 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2009 VL 37 IS 1 BP 1 EP 6 DI 10.1097/CCM.0b013e31819292ea PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 391YK UT WOS:000262269900001 PM 19050621 ER PT J AU Sun, JX Reisner, AT Saeed, M Heldt, T Mark, RG AF Sun, James X. Reisner, Andrew T. Saeed, Mohammed Heldt, Thomas Mark, Roger G. TI The cardiac output from blood pressure algorithms trial SO CRITICAL CARE MEDICINE LA English DT Article DE cardiac output; non-invasive monitoring; pulse contour; database; arterial blood pressure; thermodilution ID STROKE VOLUME; AORTIC PRESSURE; PULSE; THERMODILUTION; DATABASE; MODEL; FLOW; DOG AB Objective: The value of different algorithms that estimate cardiac output (CO) by analysis of a peripheral arterial blood pressure (ABP) waveform has not been definitively identified. In this investigation, we developed a testing data set containing a large number of radial ABP waveform segments and contemporaneous reference CO by thermodilution measurements, collected in an intensive care unit (ICU) patient population during routine clinical operations. We employed this data set to evaluate a set of investigational algorithms, and to establish a public resource for the meaningful comparison of alternative CO-from-ABP algorithms. Design: A retrospective comparative analysis of eight investigational CO-from-ABP algorithms using the Multiparameter Intelligent Monitoring in Intensive Care II database. Setting: Mixed medical/surgical ICU of a university hospital. Patients. A total of 120 cases. Interventions: None. Measurements. CO estimated by eight investigational CO-from-ABP algorithms, and COT, as a reference. Main Results: All investigational methods were significantly better than mean arterial pressure (MAP) at estimating direction changes in CO(TD). Only the formula proposed by Liljestrand and Zander in 1928 was a significantly better quantitative estimator of CO(TD) compared with MAP (95% limits-of-agreement with CO(TD): -1.76/+1.41 L/min versus -2.20/+1.82 L/min, respectively; p < 0.001, per the Kolmogorov-Smirnov test). The Liljestrand method was even more accurate when applied to the cleanest ABP waveforms. Other investigational algorithms were not significantly superior to MAP as quantitative estimators of CO. Conclusions: Based on ABP data recorded during routine intensive care unit (ICU) operations, the Liljestrand and Zander method is a better estimator Of CO(TD) than MAP alone. Our attempts to fully replicate commercially-available methods were unsuccessful, and these methods could not be evaluated. However, the data set is publicly and freely available, and developers and vendors of CO-from-ABP algorithms are invited to test their methods using these data. (Crit Care Med 2009; 37:72-80) C1 [Sun, James X.] Massachusetts Gen Hosp, MIT, Div Hlth Sci & Technol, Boston, MA 02114 USA. [Reisner, Andrew T.] Dept Emergency Med, Div Hlth Sci & Technol, Boston, MA USA. [Saeed, Mohammed] Philips Med Syst, MIT, Div Hlth Sci & Technol, Boston, MA USA. [Heldt, Thomas] MIT, Electromagnet & Elect Syst Lab, Boston, MA USA. RP Sun, JX (reprint author), Massachusetts Gen Hosp, MIT, Div Hlth Sci & Technol, Boston, MA 02114 USA. EM areisner@partners.org FU National Institute of Biomedical imaging and Bioengineering [R01 EB001659]; Philips Medical Systems and Philips Research North America; Center for the Integration of Medicine and Innovative Technology FX This research was supported by grant R01 EB001659 from the National Institute of Biomedical imaging and Bioengineering, by support from Philips Medical Systems and Philips Research North America, and by the Center for the Integration of Medicine and Innovative Technology. NR 29 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2009 VL 37 IS 1 BP 72 EP 80 DI 10.1097/CCM.0b013e3181930174 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 391YK UT WOS:000262269900010 PM 19112280 ER PT J AU Nishida, T De Yu, J Minamishima, S Sips, PY Searles, RJ Buys, ES Janssens, S Brouckaert, P Bloch, KD Ichinose, F AF Nishida, Takefumi De Yu, Jia Minamishima, Shizuka Sips, Patrick Y. Searles, Robert J. Buys, Emmanuel S. Janssens, Stefan Brouckaert, Peter Bloch, Kenneth D. Ichinose, Fumito TI Protective effects of nitric oxide synthase 3 and soluble guanylate cyclase on the outcome of cardiac arrest and cardiopulmonary resuscitation in mice SO CRITICAL CARE MEDICINE LA English DT Article DE cardiac arrest; cardiopulmonary resuscitation; nitric oxide; neurological dysfunction; myocardial dysfunction; apoptosis ID CARDIOMYOCYTE-SPECIFIC OVEREXPRESSION; REPERFUSION INJURY; KNOCKOUT MICE; DYSFUNCTION; MORTALITY; HEART; MODEL; SHOCK AB Objectives: Despite advances in resuscitation methods, survival after out-of-hospital cardiac arrest remains low, at least in part, due to postcardiac arrest circulatory and neurologic failure. To elucidate the role of nitric oxide (NO) in the recovery from cardiac arrest and cardiopulmonary resuscitation (CPR), we studied the impact of NO synthase (NOS3)/cGMP signaling on cardiac and neurologic outcomes after cardiac arrest and CPR. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: Mice. Interventions. Female wild-type (WT) mice, NOS3-deficient mice (NOS3(-/-)), NOS3(-/-) mice with cardiomyocyte-specific overexpression of NOS3 (NOS3(-/-)CSTg), and mice deficient for soluble guanylate cyclase (alpha 1 (sGC alpha 1(-/-)) were subjected to potassium-induced cardiac arrest (9 min) followed by CPR. Cardiac and neurologic function and survival were assessed up to 24 hrs post-CPR. Measurements and Main Results: Cardiac arrest and CPR markedly depressed myocardial function in NOS3(-/-) and sGC alpha(-/-) but not in WT and NOS3(-/-)CSTg. Neurologic function score and 24 hrs survival rate was lower in NOS3(-/-) and sGC alpha 1(-/-) compared with WT and NOS3(-/-)CSTg. Detrimental effects of deficiency of NOS3 or sGC alpha 1 were associated with enhanced inflammation of heart and liver and increased cell death in heart, liver, and brain that were largely prevented by cardiomyocyte-restricted NOS3 overexpression. Conclusions: These results demonstrate an important salutary impact of NOS3/sGC signaling on the outcome of cardiac arrest. Myocardial NOS3 prevented postcardiac arrest myocardial dysfunction, attenuated end-organ damage, and improved neurologic outcome and survival. Our observations suggest that enhancement Of cardiac NOS3 and/or sGC activity may improve outcome after cardiac arrest and CPR. (Crit Care Med 2009; 37:256-262) C1 [Nishida, Takefumi; De Yu, Jia; Minamishima, Shizuka; Sips, Patrick Y.; Searles, Robert J.; Buys, Emmanuel S.; Bloch, Kenneth D.; Ichinose, Fumito] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Janssens, Stefan] Univ Leuven, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. [Brouckaert, Peter] Univ Ghent, Dept Mol Biomed Res, B-9000 Ghent, Belgium. Univ Ghent VIB, Flanders Inst Biotechnol, B-9000 Ghent, Belgium. Univ Ghent VIB, Dept Mol Biol, B-9000 Ghent, Belgium. RP Nishida, T (reprint author), Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM fichinose@partners.org OI Sips, Patrick/0000-0001-9241-5980 FU UGENT-BOF-GOA; FWO-Vlaanderen; National Institute of Health [HL70896, HL71987, GM79360] FX Supported by grants from UGENT-BOF-GOA and FWO-Vlaanderen (to PB), National Institute of Health Grants HL70896 (to KDB), and HL71987 and GM79360 (to FI). The authors have not disclosed any potential conflicts of interest. NR 20 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2009 VL 37 IS 1 BP 256 EP 262 DI 10.1097/CCM.0b013e318192face PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 391YK UT WOS:000262269900035 PM 19050616 ER PT J AU Querques, J AF Querques, John TI Can reading a diary improve psychological outcomes in the intensive care unit? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE diaries; intensive care; anxiety; depression; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; ICU C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Querques, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2009 VL 37 IS 1 BP 356 EP 357 DI 10.1097/CCM.0b013e3181930399 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 391YK UT WOS:000262269900065 PM 19112304 ER PT J AU Greer, DM AF Greer, David M. TI Respecting patients' rights at the end of life: Problems with the 2006 Uniform Anatomical Gift Act SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE organ donation; brain death; end-of-life care C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Greer, DM (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2009 VL 37 IS 1 BP 372 EP 373 DI 10.1097/CCM.0b013e3181932d71 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 391YK UT WOS:000262269900075 PM 19112314 ER PT J AU Del Sorbo, L Thompson, BT Ranieri, VM AF Del Sorbo, Lorenzo Thompson, B. Taylor Ranieri, V. Marco TI Postregistration trials: Should we? How do we? SO CRITICAL CARE MEDICINE LA English DT Article DE postregistration trials; postmarketing; phase IV; placebo; ethics; sponsored research; activated protein C; drotrecogin alfa; sepsis; septic shock ID ACTIVATED PROTEIN-C; PLACEBO-CONTROLLED TRIALS; GUIDELINES RECOMMEND THERAPY; RANDOMIZED CONTROLLED-TRIAL; SURVIVING SEPSIS CAMPAIGN; HUMAN MONOCLONAL-ANTIBODY; SEPTIC SHOCK; DOUBLE-BLIND; CLINICAL-RESEARCH; DRUG SAFETY AB Postregistration trials or postmarketing or phase IV trials are tools to investigate any treatment that is already approved and is, therefore, available for prescription use. The main objectives of these trials are typical effectiveness, more structured surveillance for uncommon or rare side effects, and the potential development of new indications. Several issues need to be addressed in the postregistration phase of the evaluation of a therapeutic treatment. Among those we will focus on two ethical challenges: reporting bias from industry-sponsored research and use of placebo as one of the arms in controlled studies where proven treatment already exists. The review of this topic is particularly relevant in the field of critical care because it is ongoing in the debate about the opportunity to perform a new placebo-controlled study with the recombinant human activated protein C (activated drotrecogin alfa-activated protein C). In fact, despite the approval of activated protein C for treatment of patients with severe sepsis and high risk of death, several issues regarding the efficacy and safety of its administration have been recognized by several investgators to the point that the European Medicines Agency asked for a new placebo-controlled study to further clarify the benefit/risk profile of activated protein C. (Crit Care Med 2009; 37[Suppl.]: S154-S158) C1 [Del Sorbo, Lorenzo; Ranieri, V. Marco] Univ Turin, Osped S Giovanni Battista Molinette, Dipartimento Anestesiol & Rianimaz, Turin, Italy. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Del Sorbo, L (reprint author), Univ Turin, Osped S Giovanni Battista Molinette, Dipartimento Anestesiol & Rianimaz, Turin, Italy. EM marco.ranieri@unito.it OI Del Sorbo, Lorenzo/0000-0003-3294-9838 FU Italian Ministry of University and Research [215.04-06]; Regione Piemonte [ASZ25-06-07] FX Supported, in part, by Italian Ministry of University and Research (215.04-06), Regione Piemonte (integrated project ASZ25-06-07). NR 51 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2009 VL 37 IS 1 BP S154 EP S158 DI 10.1097/CCM.0b013e3181922b9b PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 391YO UT WOS:000262270300022 PM 19104216 ER PT J AU Sahai, I Marsden, D AF Sahai, Inderneel Marsden, Deborah TI Newborn Screening SO CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES LA English DT Review DE Biotinidase deficiency; congenital adrenal hyperplasia; cystic fibrosis; false negatives; false positives; galactosemias; hemoglobin disorders; hypothyroidism; lysosomal storage disorders; metabolic disorders; positive predictive value; tandem mass spectrometry; specimen collection; second-tier tests ID TANDEM MASS-SPECTROMETRY; DRIED BLOOD SPOTS; CONGENITAL ADRENAL-HYPERPLASIA; COA DEHYDROGENASE-DEFICIENCY; 3-METHYLCROTONYL-COA CARBOXYLASE DEFICIENCY; PERFORMANCE LIQUID-CHROMATOGRAPHY; PHENYLALANINE-RESTRICTED DIET; DIRECT MULTIPLEX ASSAY; FAST ATOM BOMBARDMENT; FATTY-ACID OXIDATION AB Screening newborns for inherited disorders provides an opportunity for pre-symptomatic identification and early intervention to prevent or mitigate morbidity and mortality associated with these conditions. Since the introduction of newborn screening in 1962 to screen for phenylketonuria, technological advances have enabled the screening panel to expand substantially so that it now includes more than 50 disorders. Newborn screening will continue to evolve,, and deployment of improved methodologies and incorporation of additional disorders are expected. This article provides an overview of the current state of newborn screening, and describes the disorders detectable, the methodologies employed, and the challenges involved in analyses of specimens obtained from newborns. C1 [Sahai, Inderneel] Univ Massachusetts, New England Newborn Screening Program, Jamaica, NY USA. [Sahai, Inderneel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marsden, Deborah] Harvard Univ, Sch Med, Boston, MA USA. [Marsden, Deborah] Childrens Hosp Boston, Boston, MA 02115 USA. RP Marsden, D (reprint author), Childrens Hosp Boston, Fegan 10,300 Longwood Ave, Boston, MA 02115 USA. EM deborah.marsden@childrens.harvard.edu NR 143 TC 22 Z9 27 U1 8 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8363 J9 CRIT REV CL LAB SCI JI Crit. Rev. Clin. Lab. Sci. PY 2009 VL 46 IS 2 BP 55 EP 82 AR PII 909183135 DI 10.1080/10408360802485305 PG 28 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 413TC UT WOS:000263814400001 PM 19255915 ER PT J AU Soltanoff, CS Chen, W Yang, S Li, YP AF Soltanoff, Carrie S. Chen, Wei Yang, Shuying Li, Yi-Ping TI Signaling Networks that Control the Lineage Commitment and Differentiation of Bone Cells SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE osteoblasts; osteoclasts; signaling pathways; transcriptional regulation; skeletal disease; bone genes ID NF-KAPPA-B; COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR PU.1; GROWTH-FACTOR-BETA; ACTIVATED PROTEIN-KINASE; OSTEOCLAST-ASSOCIATED RECEPTOR; SYMPATHETIC-NERVOUS-SYSTEM; MESENCHYMAL STEM-CELLS; CYTOKINE-MEDIATED OSTEOCLASTOGENESIS; INHIBITS OSTEOBLAST DIFFERENTIATION AB Osteoblasts and osteoclasts are the two major bone cells involved in the bone remodeling process. Osteoblasts are responsible for bone formation while osteoclasts are the bone-resorbing cells. The major event that triggers osteogenesis and bone remodeling is the transition of mesenchymal stem cells into differentiating osteoblast cells and monocyte/macrophage precursors into differentiating osteoclasts. Imbalance in differentiation and function of these two cell types will result in skeletal diseases such as osteoporosis, Paget's disease, rheumatoid arthritis, osteopetrosis, periodontal disease, and bone cancer metastases. Osteoblast and osteoclast commitment and differentiation are controlled by complex activities involving signal transduction and transcriptional regulation of gene expression. Recent advances in molecular and generic studies using gene targeting in mice enable a better understanding of the multiple factors and signaling networks that control the differentiation process at a molecular level. This review summarizes recent advances in studies of signaling transduction pathways and transcriptional regulation of osteoblast and osteoclast cell lineage commitment and differentiation. Understanding the signaling networks that control the commitment and differentiation of bone cells will not only expand our basic understanding of the molecular mechanisms of skeletal development but will also aid our ability to develop therapeutic means of intervention in skeletal diseases. C1 [Soltanoff, Carrie S.; Chen, Wei; Yang, Shuying; Li, Yi-Ping] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Chen, Wei; Yang, Shuying; Li, Yi-Ping] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM ypli@forsyth.org RI Yang, Shuying/G-4599-2011 FU NIH [AR44741 (Y.-P. Li), AR-48133 (Y.-P. Li)] FX We would like to thank Ning Li for his assistance with the manuscript. We apologize to the many researchers whose work could not be cited due to space limitations. Work in our laboratory is supported by grants by NIH grant AR44741 (Y.-P. Li) and AR-48133 (Y.-P. Li). NR 390 TC 59 Z9 70 U1 0 U2 18 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1045-4403 EI 2162-6502 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 2009 VL 19 IS 1 BP 1 EP 46 PG 46 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 403OU UT WOS:000263092700001 PM 19191755 ER PT J AU Ginde, AA Mansbach, JM Camargo, CA AF Ginde, Adit A. Mansbach, Jonathan M. Camargo, Carlos A., Jr. TI Vitamin D, Respiratory Infections, and Asthma SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review ID D-RECEPTOR GENE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; SERUM 25-HYDROXYVITAMIN-D; D SUPPLEMENTATION; D DEFICIENCY; MYCOBACTERIUM-TUBERCULOSIS; 1,25-DIHYDROXYVITAMIN D-3; BIRTH COHORT; T-CELLS AB Over the past decade, interest has grown in the role of vitamin D in many nonskeletal medical conditions, including respiratory infection. Emerging evidence indicates that vitamin D-mediated innate immunity, particularly through enhanced expression of the human cathelicidin antimicrobial peptide (hCAP-18), is important in host defenses against respiratory tract pathogens. Observational studies suggest that vitamin D deficiency increases risk of respiratory infections. This increased risk may contribute to incident wheezing illness in children and adults and cause asthma exacerbations. Although unproven, the increased risk of specific respiratory infections in susceptible hosts may contribute to some cases of incident asthma. Vitamin D also modulates regulatory T-cell function and interleukin-10 production, which may increase the therapeutic response to glucocorticoids in steroid-resistant asthma. Future laboratory, epidemiologic, and randomized interventional studies are needed to better understand vitamin D's effects on respiratory infection and asthma. C1 [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU NHLBI NIH HHS [R01 HL84401] NR 56 TC 93 Z9 103 U1 1 U2 10 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD JAN PY 2009 VL 9 IS 1 BP 81 EP 87 DI 10.1007/s11882-009-0012-7 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 425ZB UT WOS:000264675700012 PM 19063829 ER PT J AU Wang, JH Cao, ZX Li, SQ AF Wang, Jihua Cao, Zanxia Li, Shuqiang TI Molecular Dynamics Simulations of Intrinsically Disordered Proteins in Human Diseases SO CURRENT COMPUTER-AIDED DRUG DESIGN LA English DT Article DE Intrinsically disordered proteins; molecular dynamics simulations; P53; alpha-synuclein; drug discovery ID ALPHA-SYNUCLEIN AGGREGATION; DNA-BINDING DOMAIN; N-TERMINAL DOMAIN; P53 CORE DOMAIN; FORCE-FIELD; TRANSACTIVATION DOMAIN; FUNCTIONAL ANTHOLOGY; UNSTRUCTURED PROTEINS; P53-MDM2 INTERACTION; STRUCTURAL BASIS AB Recent structural and genomic studies have clearly shown that many proteins contain long regions that do not adopt any globular structures under native conditions. These regions are termed intrinsically disordered or unstructured, and the proteins with intrinsically disordered regions are called intrinsically disordered proteins (IDPs). Current studies estimate that one third of eukaryotic proteins contain stretches of at least 30 contiguous disordered residues, the predictions are even higher in cancer-associated and signaling proteins (80% and 67%, respectively). IDPs play crucial roles in many aspects of molecular and cell biology and numerous IDPs are associated with human diseases such as cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, diabetes and others. IDPs such as tumor suppressor P53, BRCA1, Parkinson's protein alpha-synuclein, Alzheimer disease protein tau and many other diseaseassociated hub proteins represent attractive targets for drugs modulating protein-protein interactions. The structures and dynamics of the disordered proteins are the basis for the novel drug discovery. IDPs are lack of stable tertiary and / or secondary structure under physiological conditions in vitro. It is difficult to obtain accurate experimental measurements for the structures and dynamics of the disordered proteins. Molecular dynamics simulations provide available powerful tools to calculate the structures and their related dynamics of IDPs. In this paper, we focus on structural and dynamics insights of disease-associated disordered proteins by molecular dynamics simulations. C1 [Wang, Jihua; Cao, Zanxia] Dezhou Univ, Key Lab Biophys, Shandong Univ, Dezhou 253023, Shandong, Peoples R China. [Li, Shuqiang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, JH (reprint author), Dezhou Univ, Key Lab Biophys, Shandong Univ, Dezhou 253023, Shandong, Peoples R China. EM jhwyh@yahoo.com.cn FU Chinese National Key Fundamental Research Project; Shandong Fundamental Research [90403120, Y 2005D12]; Dezhou University FX This work was supported by the Chinese National Key Fundamental Research Project and Shandong Fundamental Research ( Grant No. 90403120 and Grant No. Y 2005D12). We thank Dezhou University for financial support. NR 71 TC 10 Z9 11 U1 5 U2 30 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4099 J9 CURR COMPUT-AID DRUG JI Curr. Comput.-Aided Drug Des. PY 2009 VL 5 IS 4 BP 280 EP 287 PG 8 WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Computer Science GA 523PG UT WOS:000272085700005 ER PT J AU Pallikaris, A Skondra, D Karavvela, M Tsilimbaris, M AF Pallikaris, Aristophanis Skondra, Dimitra Karavvela, Marieta Tsilimbaris, Miltiadis TI Confocal Scanning Laser Tomography Analysis of Choroidal Neovascularization and Correlation with Quantitative Fluorescein Angiography SO CURRENT EYE RESEARCH LA English DT Article DE age-related macular degeneration; confocal scanning laser ophthalmoscopy; fluorescein angiography; photodynamic therapy; retinal imaging ID OPTICAL COHERENCE TOMOGRAPHY; RANDOMIZED CLINICAL-TRIAL; DIABETIC MACULAR EDEMA; REPORT NO. 1; PHOTODYNAMIC THERAPY; PATHOLOGICAL MYOPIA; VERTEPORFIN THERAPY; VISUAL FUNCTION; DEGENERATION; MEMBRANES AB Purpose: To investigate the agreement between confocal scanning laser tomography and quantitative fluorescein angiography in the analysis of retinal-thickness changes in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Materials and Methods: The edema index of a cSLT was measured in 18 eyes of 16 patients with CNV secondary to AMD that underwent photodynamic therapy (PDT) with Visudyne. Measurements were taken 1 hour before as well as 1 hour, 1 month, and 3 months after therapy. Moreover, a custom-written algorithm was used to analyze the integrated contrast amplitude (ICA) of fluorescein angiograms acquired before as well as 1 month and 3 months after PDT. Confocal scanning laser analysis of the edema index (EI) before and after PDT and correlation of the results with quantitative fluorescein angiography was performed. Results: A statistical significant increase of the EI was observed 1 hour after PDT. Nonetheless, no other statistical significant change over time was observed either on the EI or the ICA. Significant correlation was observed between the EI and the ICA as well as their changes over time, yet better results were observed when non-parametric correlation was calculated.Conclusions: The axial intensity profile of the cSLT and the edema index provide important information with respect to the neovascular membranes and correlate well with quantitative fluorescein angiography. The application of cSLT and the EI provide an important tool that could complement the investigation of new treatments of neovascular membranes. C1 [Pallikaris, Aristophanis; Karavvela, Marieta; Tsilimbaris, Miltiadis] Univ Crete, Inst Vis & Opt, Iraklion 71003, Greece. [Skondra, Dimitra] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pallikaris, A (reprint author), Univ Crete, Inst Vis & Opt, Iraklion 71003, Greece. EM apallik@med.uoc.gr NR 32 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 2009 VL 34 IS 4 BP 319 EP 327 AR PII 910508903 DI 10.1080/02713680902796153 PG 9 WC Ophthalmology SC Ophthalmology GA 434RT UT WOS:000265292500010 PM 19373581 ER PT J AU Framme, C Walter, A Prahs, P Regler, R Theisen-Kunde, D Alt, C Brinkmann, R AF Framme, Carsten Walter, Andreas Prahs, Philipp Regler, Roman Theisen-Kunde, Dirk Alt, Clemens Brinkmann, Ralf TI Structural Changes of the Retina after Conventional Laser Photocoagulation and Selective Retina Treatment (SRT) in Spectral Domain OCT SO CURRENT EYE RESEARCH LA English DT Article DE autofluorescence; imaging; OCT; retinal laser treatment; SRT ID PIGMENT EPITHELIUM; PRIMATE RETINA; FUNDUS AUTOFLUORESCENCE; MACULAR DEGENERATION; KRYPTON; LESIONS; RPE; DISEASES; CULTURE; BARRIER AB Background: Spectral domain optical coherence tomography (SD-OCT) in patients can deliver retinal cross-sectional images with high resolution. This may allow the evaluation of the extent of damage to the retinal pigment epithelium (RPE) and the neurosensory retina after laser treatment. This article aims to investigate the value of SD-OCT in comparing laser lesions produced by conventional laser photocoagulation and selective retina treatment (SRT). Material and Methods: In a retrospective study, conventional retinal laser (CRL) lesions and SRT laser lesions were evaluated with SD-OCT. One hundred seventy-five CRL lesions were investigated in 10 patients with diabetic maculopathy at timepoints between 1 hr and 4 years after treatment. Ninety-one SRT lesions were examined in 9 patients with central serous retinopathy, geographic atrophy, and diabetic maculopathy at timepoints between 1 hr and 2 years. CRL lesions were applied with an ophthalmoscopically slightly grayish-white appearance (Nd:YAG laser at 532-nm wavelength; power 100-200 mW; retinal spot diameter 100 mu m; pulse duration 100 ms). SRT lesions were applied with a Nd:YLF (527 nm; pulse duration 200 ns [30 pulses at 100 Hz]; energy 100-200 mu J/pulse; retinal spot diameter 200 mu m) and were visible only angiographically. Results: All CRL lesions were characterized by high reflectivity in OCT images throughout the full thickness of the neurosensory tissue 1 hr after irradiation, suggesting complete neurosensory coagulation. Strong contraction through the full thickness of the neurosensory layers was observed within 7 days after treatment. In contrast, the neural retina appeared unaffected after SRT. For both lesion types, the RPE layer appeared to be regular or thinner immediately after treatment, whereas within a period of 4 weeks, a RPE thickening indicating RPE proliferation was observable. One year and later after treatment, CRL lesions were characterized by RPE atrophy combined with significant damage of the neurosensory tissue. SRT lesions aged one year and older revealed unaffected neurosensory structures and an intact RPE layer. Conclusion: Spectral domain OCT can be used clinically to follow the development of laser-induced lesions over time. Postoperative RPE proliferation was observed in both CRL and SRT laser lesions. RPE atrophy appeared subsequently only in CRL lesions, whereas the neurosensory retina appeared unaffected following SRT. These results suggest the selective effect of SRT in humans without causing adverse effects to the neurosensory retina. C1 [Framme, Carsten; Walter, Andreas; Prahs, Philipp; Regler, Roman] Univ Eye Hosp Regensburg, D-93042 Regensburg, Germany. [Theisen-Kunde, Dirk; Brinkmann, Ralf] Med Laser Ctr, Lubeck, Germany. [Alt, Clemens] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Framme, C (reprint author), Univ Eye Hosp Regensburg, Franz Josef Strauss Allee 11, D-93042 Regensburg, Germany. EM carsten.framme@klinik.uni-regensburg.de RI Brinkmann, Ralf/E-6701-2012 FU Dr. Werner Jackstaedt foundation in Wuppertal, Germany FX The authors would like to thank the Dr. Werner Jackstaedt foundation in Wuppertal, Germany, for the generous financial support of this ongoing study. NR 29 TC 33 Z9 36 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 2009 VL 34 IS 7 BP 568 EP 579 DI 10.1080/02713680902964892 PG 12 WC Ophthalmology SC Ophthalmology GA 482JH UT WOS:000268881600007 PM 19899970 ER PT J AU Mladkova, N Chakravarti, A AF Mladkova, Nikol Chakravarti, Arnab TI Molecular Profiling in Glioblastoma: Prelude to Personalized Treatment SO CURRENT ONCOLOGY REPORTS LA English DT Article ID NEWLY-DIAGNOSED GLIOBLASTOMA; MALIGNANT GLIOMAS; IMATINIB MESYLATE; PHASE-I/II; SURVIVAL; CLASSIFICATION; TEMOZOLOMIDE; INHIBITORS; RAPAMYCIN; RECEPTOR AB The purpose of this review is to provide an up-to-date summary of the current knowledge and understanding of the molecular alterations and pathways relevant to the clinical outcome of glioblastoma patients and their potential use in designing personalized treatment for these patients. This article also discusses the potential of molecular profiling as a diagnostic modality, possible therapeutic implications of MGMT promoter methylation, the targeted inhibition of angiogenesis, and assessment of the tumor's molecular background with respect to PI3K/AKT pathway activation and associated molecules (EGFR, EGFRvIII, PTEN). C1 [Chakravarti, Arnab] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org NR 48 TC 12 Z9 13 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 EI 1534-6269 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD JAN PY 2009 VL 11 IS 1 BP 53 EP 61 PG 9 WC Oncology SC Oncology GA V16AY UT WOS:000207843700010 PM 19080742 ER PT J AU Mrugala, MM Rubenstein, JL Ponzoni, M Batchelor, TT AF Mrugala, Maciej M. Rubenstein, James L. Ponzoni, Maurilio Batchelor, Tracy T. TI Insights Into the Biology of Primary Central Nervous System Lymphoma SO CURRENT ONCOLOGY REPORTS LA English DT Article ID B-CELL LYMPHOMA; PRIMARY CNS LYMPHOMA; BCL-6 EXPRESSION; GENE-EXPRESSION; BRAIN LYMPHOMA; SURVIVAL; VIRUS; EPIDEMIOLOGY; PATHOGENESIS; OSTEOPONTIN AB Primary central nervous system lymphoma (PCNSL) is a rare variant of non-Hodgkin lymphoma that is confined to the central nervous system. Biologic studies of PCNSL are challenging to conduct because the disease is rare and available tissue material is sparse. However, in recent years there has been progress in the understanding of PCNSL biology, largely as the result of multicenter studies using modern molecular techniques. Recent studies may improve insight into the pathogenesis of PCNSL and increase the chances of identifying prognostic factors and novel therapeutic targets. This review discusses recent advances in PCNSL biology, including immunologic and genetic risk factors, and focuses on the molecular alterations important in central nervous system lymphomagenesis. C1 [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org FU NCI NIH HHS [K23 CA100291, R01 CA139083, R13 CA124293] NR 58 TC 9 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD JAN PY 2009 VL 11 IS 1 BP 73 EP 80 PG 8 WC Oncology SC Oncology GA V16AY UT WOS:000207843700013 PM 19080745 ER PT J AU Barrett, CD Di Biase, L Natale, A AF Barrett, Conor D. Di Biase, Luigi Natale, Andrea TI How to identify and treat patient with pulmonary vein stenosis post atrial fibrillation ablation SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE atrial fibrillation; catheter ablation; complications; pulmonary vein stenosis ID RADIOFREQUENCY CATHETER ABLATION; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY; VENOUS STENOSIS; FOLLOW-UP; ANGIOPLASTY; OCCLUSION; SAFETY; STENT AB Purpose of review The diagnosis of pulmonary vein stenosis, following catheter ablation of atrial fibrillation, potentially carries significant morbidity for affected patients. It is important that physicians remain aware of the entity and have an understanding of how to treat such patients. There has been controversy in how to assess patients following atrial fibrillation ablation, and how to treat asymptomatic patients with pulmonary vein stenosis. This article reviews the recently published data. Recent findings The reported incidence of pulmonary vein stenosis is decreasing. Nonetheless, it may not be found if not sought, as even patients with severe pulmonary vein stenosis may be asymptomatic. Also, patients with symptoms may be misdiagnosed if pulmonary vein stenosis is not included in the differential diagnosis. Computed tomography (CT) and MRI have been shown to be the diagnostic modalities of choice. The treatment options for severe pulmonary vein stenosis and occlusion are primarily that of pulmonary vein angioplasty with or without stenting. Despite the observed rate of restenosis, patients derive benefit from pulmonary vein angioplasty. Summary The best imaging modalities to assess for pulmonary vein stenosis are CT and MRI. Early intervention in symptomatic patients with severe pulmonary vein stenosis is warranted; in asymptomatic patients, the data suggest that such patients will also derive benefit. C1 [Di Biase, Luigi] Univ Texas Austin, Med Branch Austin, Texas Cardiac Arrhythmia Inst, Med Branch Austin, Austin, TX 78712 USA. [Natale, Andrea] Stanford Univ, Div Cardiol, Palo Alto, CA 94304 USA. [Natale, Andrea] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Barrett, Conor D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA USA. [Di Biase, Luigi] Univ Foggia, Dept Cardiol, Foggia, Italy. RP Natale, A (reprint author), 1015 E 32 St,Suite 516, Austin, TX 78705 USA. EM dr.natale@gmail.com OI Di Biase, Luigi/0000-0001-6508-4047 NR 24 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD JAN PY 2009 VL 24 IS 1 BP 42 EP 49 DI 10.1097/HCO.0b013e32831bef70 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 392SS UT WOS:000262323100007 PM 19102037 ER PT J AU Stankiewicz, JM Brass, SD AF Stankiewicz, James M. Brass, Steven D. TI Role of iron in neurotoxicity: a cause for concern in the elderly? SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE Alzheimer's disease; iron; Parkinson's disease; stroke ID EARLY PARKINSON-DISEASE; REDOX-ACTIVE IRON; ALZHEIMERS-DISEASE; BRAIN IRON; NEURODEGENERATIVE DISEASES; INTRACEREBRAL HEMORRHAGE; OXIDATIVE STRESS; ACCUMULATION; METABOLISM; DISORDERS AB Purpose of review To explore the role of iron physiology in the brain of healthy adults and review how increased brain iron deposition has been associated with common neurodegenerative diseases that affect the elderly. Recent findings Because iron plays a role in oxygen transportation, myelin synthesis, neurotransmitter production, and electron transfers, it serves as a crucial cofactor in normal central nervous metabolism. However, an increased level of brain iron may promote neurotoxicity due to free radical formation, lipid peroxidation, and ultimately, cellular death. Advanced neuroimaging techniques and pathological studies have demonstrated increased brain iron with aging, and increased iron deposition has also been observed in patients with a constellation of neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. Summary Pathologic and neurologic imaging coupled with experimentation have increased our understanding of the link between iron and neurodegeneration. A potential implication is that disease-modifying therapies aimed at removing excess iron may one day be part of the armamentarium employed by clinicians to decrease the burden of neurodegenerative diseases in the elderly. C1 [Stankiewicz, James M.; Brass, Steven D.] Partners MS Ctr, Dept Neurol, Brigham & Womens Hosp, Brookline, MA 02445 USA. [Brass, Steven D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Stankiewicz, JM (reprint author), Partners MS Ctr, Dept Neurol, Brigham & Womens Hosp, 1 Brookline Pl W,Suite 225, Brookline, MA 02445 USA. EM jstankiewicz@partners.org NR 71 TC 41 Z9 44 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD JAN PY 2009 VL 12 IS 1 BP 22 EP 29 DI 10.1097/MCO.0b013e32831ba07c PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 391CN UT WOS:000262210800004 PM 19057183 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI Angiotensin-converting enzyme 2: implications for blood pressure and kidney disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE angiotensin-converting enzyme; angiotensin-converting enzyme 2; angiotensin 1-7; angiotensin 1-9; angiotensin II; renin-angiotensin system ID GENE ACE2 POLYMORPHISMS; ESSENTIAL-HYPERTENSION; DIABETIC-NEPHROPATHY; HAN CHINESE; ANGIOTENSIN-CONVERTING-ENZYME-2; EXPRESSION; ASSOCIATION; HEART; OVEREXPRESSION; INJURY AB Purpose of review Angiotensin-converting enzyme 2 (ACE 2), the main product of which is Ang 1-7, which binds to its receptor, Mas, is an important member of the renin-angiotensin system. Recent findings A substantial body of research indicates that ACE2 is cardioprotective and renoprotective. ACE2 participates in a pathway that is counterregulatory to the effects of angiotensin II (Ang II). The mechanisms by which the protective effects of ACE2 occur are just beginning to be elucidated. Summary As ACE2 appears to exert protective effects within the kidney and vasculature, recent data indicate that how it is expressed, what regulates it, and how it interacts with other biological systems may ultimately have clinical implications. C1 [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Yawkey 6C,55 Fruit St, Boston, MA 02114 USA. EM jingelfinger@partners.org NR 44 TC 33 Z9 35 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JAN PY 2009 VL 18 IS 1 BP 79 EP 84 DI 10.1097/MNH.0b013e32831b70ad PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 392SU UT WOS:000262323300014 PM 19077694 ER PT J AU Pittet, MJ AF Pittet, Mikael J. TI Behavior of immune players in the tumor microenvironment SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE imaging; immunotherapy; in vivo; macrophages; T cells ID REGULATORY T-CELLS; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; MELANOMA PATIENTS; DENDRITIC CELLS; MAMMARY-TUMORS; QUANTUM DOTS; CANCER; ANTIGEN; ANGIOGENESIS AB Purpose of review Tumors recruit various immune cells with seemingly contrasting functions. Yet, the precise role of these cells in situ remains vastly unknown. This review presents a new discovery effort that employs intravital imaging to study immune players directly in tissues. Recent findings Cytotoxic T lymphocytes (CTLs) that recognize cognate antigenic peptide can infiltrate tumors from the periphery to the center, and physically engage and eliminate antigen-presenting tumor cells. Nevertheless, the reported kinetics for tumor cell killing by CTLs in vivo is surprisingly low as it takes several hours for one CTL to eliminate one tumor cell. Also, T regulatory (Treg) cells can create a suppressive milieu that restricts the release of CTL cytotoxic granules, which protects tumor cells from being killed. CTLs may be further subverted during lengthy interactions with tumor-associated macrophages (TAMs). Finally, TAMs can directly facilitate tumor invasion by recruiting tumor cells nearby vessels and promoting their intravasation. S Summary Intravital imaging has started to uncover tumor-related immune events as they unfold in vivo. The technology should be exploited in the coming years to dissect further the tumor microenvironment and to define therapeutics that augment antitumor immunity. C1 [Pittet, Mikael J.] Harvard Univ, Sch Med, Ctr Syst Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Pittet, MJ (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu FU NIH [5P50-CA86355, U54-CAl 26515] FX I thank Drs. Ralph Weissleder and Thorsten Mempel for critical reading of the manuscript. M.J.P. is funded in part by NIH 5P50-CA86355 and NIH U54-CAl 26515. NR 63 TC 41 Z9 46 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JAN PY 2009 VL 21 IS 1 BP 53 EP 59 DI 10.1097/CCO.0b013e32831bc38a PG 7 WC Oncology SC Oncology GA 392XU UT WOS:000262336300010 PM 19125019 ER PT J AU Moore, SA AF Moore, Sally A. TI Cognitive abnormalities in posttraumatic stress disorder SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE cognition; information processing; memory; posttraumatic stress disorder; trauma ID AUTOBIOGRAPHICAL MEMORY SPECIFICITY; FALSE MEMORIES; INTERPERSONAL TRAUMA; OVERGENERAL MEMORY; EXECUTIVE CONTROL; INVENTORY PTCI; PTSD; DEPRESSION; SYMPTOMS; VICTIMS AB Purpose of review The current review aims to describe and evaluate research on cognitive difficulties associated with posttraumatic stress disorder (PTSD) published between January 2007 and June 2008. Recent findings The reviewed studies provide additional evidence that negative appraisals and decrements on verbal and autobiographical memory tasks are exhibited by individuals with PTSD relative to controls and may represent preexisting risk factors for PTSD rather than a result or concomitant of PTSD symptoms. In addition, the reviewed findings provide further evidence for source monitoring difficulties and attentional biases toward trauma-relevant information in PTSD. Recent research also provides evidence that, although memories of traumatic events differ in PTSD relative to other types of memories and memories of depressed individuals, they are likely on the same continuum as nontraumatic memories rather than qualitatively different. Summary Individuals with PTSD experience cognitive alterations ranging from impairments in overall memory functioning to difficulties specific to trauma-related cues. These cognitive difficulties appear to be importantly related to the development and/or maintenance of the disorder. At this point, it is unclear whether common mechanisms may account for these diverse cognitive difficulties and whether cognitive impairments are attributable to comorbid depression. C1 [Moore, Sally A.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Moore, Sally A.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Moore, SA (reprint author), VA Puget Sound Healthcare Syst, MH 116,1660 S Columbian Way, Seattle, WA 98108 USA. EM sally.moore2@va.gov NR 55 TC 37 Z9 38 U1 5 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2009 VL 22 IS 1 BP 19 EP 24 DI 10.1097/YCO.0b013e328314e3bb PG 6 WC Psychiatry SC Psychiatry GA 393UH UT WOS:000262398400005 PM 19122530 ER PT J AU Hulick, PJ Noonan, KM Kulkarni, S Donovan, DJ Listewnik, M Ihm, C Stoler, JM Weremowicz, S AF Hulick, P. J. Noonan, K. M. Kulkarni, S. Donovan, D. J. Listewnik, M. Ihm, C. Stoler, J. M. Weremowicz, S. TI Cytogenetic and Array-CGH Characterization of a Complex de novo Rearrangement Involving Duplication and Deletion of 9p and Clinical Findings in a 4-Month-Old Female SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article DE aCGH; Cleft palate; Deletion 9p; Duplication 9p; FISH; Inversion 9p ID SHORT-ARM; CRITICAL REGION; CHROMOSOME 9P; SEX-REVERSAL; TRISOMY; ORIGIN; RETARDATION; DELINEATION; PHENOTYPE; GENE(S) AB Approximately 15 patients with partial trisomy 9p involving de novo duplications have been previously described. Here, we present clinical, cytogenetic, FISH and aCGH findings in a patient with a de novo complex rearrangement in the short arm of chromosome 9 involving an inverted duplication at 9p24 -> p21.3 and a deletion at 9pter -> p24.2. FISH probes generated from BACs selected from the UCSC genome browser were utilized to verify this rearrangement. It is likely that some previously described duplications of 9p may also be products of complex chromosomal aberrations. This report in which FISH and aCGH were used to more comprehensively characterize the genomic rearrangement in a patient with clinical manifestations of 9p duplication syndrome underscores the importance of further characterizing cytogenetically detected rearrangements. Copyright (C) 2009 S. Karger AG, Basel C1 [Kulkarni, S.; Donovan, D. J.; Listewnik, M.; Ihm, C.; Weremowicz, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hulick, P. J.; Noonan, K. M.; Stoler, J. M.] Med Genet Program, Harvard Partners Ctr Genet & Gen, Boston, MA USA. [Hulick, P. J.; Noonan, K. M.; Stoler, J. M.] MGH Clin, Boston, MA USA. [Noonan, K. M.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Stoler, J. M.; Weremowicz, S.] Harvard Univ, Sch Med, Boston, MA USA. RP Weremowicz, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM sweremowicz@partners.org RI Donovan, Diana/A-1256-2010 NR 38 TC 13 Z9 13 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2009 VL 126 IS 3 BP 305 EP 312 DI 10.1159/000251966 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 543BO UT WOS:000273545100007 PM 20068300 ER PT J AU Kim, PG Daley, GQ AF Kim, Peter Geon Daley, George Q. TI Application of induced pluripotent stem cells to hematologic disease SO CYTOTHERAPY LA English DT Review DE hematopoiesis; hematopoietic stem cells; pluripotent stem cells; regenerative medicine; signal transduction; transcription factors ID SMALL-MOLECULE COMPOUNDS; HUMAN SOMATIC-CELLS; MURINE YOLK-SAC; HEMATOPOIETIC PROGENITORS; HUMAN FIBROBLASTS; DEFINED FACTORS; SELF-RENEWAL; IPS CELLS; REPROGRAMMING FACTORS; GENE-THERAPY AB Induced pluripotent stem cells (iPSC) were first generated from somatic cells via the transduction of time 'Yamanaka' factors, Oct4, Sox2, KIP and c-Mye. Because iPSC are similar to embryonic stem cells (ESC) and can be differentiated into any cell type of choice, iPSC have the potential to become a platform fur personalised medicine by allowing a patient's own cells to become a source of therapeutic tissue. This review describes the main challenges in iPSC technology by focusing on its application to hematologic diseases. The explosive interest in improving iPSC technology has generated numerous genetic and chemical methods for iPSC derivation, but these methods must be evaluated comparatively for their safety and efficacy because there are risks of genetic abnormalities and oncogenesis. Competent iPSC will need to be selected carefully based on physical, genetic and functional criteria, and differentiated efficiently into hematopoietic stem calls via modulation of sevenal signaling pathways before they prove valuable in the clinic. C1 [Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med,Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst,Manton Ctr Orphan Dis Res, Div Hematol,Brigham & Womens Hosp,Howard Hughes M, Boston, MA 02115 USA. Harvard Stem Cell Inst, Cambridge, MA USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu NR 110 TC 12 Z9 14 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2009 VL 11 IS 8 BP 980 EP 989 DI 10.3109/14653240903348319 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 579EQ UT WOS:000276350900002 PM 19929461 ER PT J AU Johnson, JG First, MB Block, S Vanderwerker, LC Zivin, K Zhang, BH AF Johnson, Jeffrey G. First, Michael B. Block, Susan Vanderwerker, Lauren C. Zivin, Kara Zhang, Baohui TI Stigmatization and Receptivity to Mental Health Services Among Recently Bereaved Adults SO DEATH STUDIES LA English DT Article ID COMPLICATED GRIEF; TRAUMATIC GRIEF; DISORDER DISTINCT; DEPRESSION; STIGMA; REPLICATION; SYMPTOMS; CRITERIA; ILLNESS; ANXIETY AB Severe grief symptoms, treatment receptivity, attitudes about grief, and stigmatization concerns were assessed in a community-based sample of 135 widowed participants in the Yale Bereavement Study. There was a statistically significant association between the severity of grief symptoms and reported negative reactions from friends and family members. However, more than 90% of the respondents with complicated grief, a severe grief disorder, reported that they would be relieved to know that having such a diagnosis was indicative of a recognizable psychiatric condition, and 100% reported that they would be interested in receiving treatment for their severe grief symptoms. C1 [Johnson, Jeffrey G.; First, Michael B.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Johnson, Jeffrey G.; First, Michael B.] Columbia Univ, Dept Psychiat, New York, NY USA. [Block, Susan] Brigham & Womens Hosp, Ctr Psychosocial Oncol & Palliat Care Res, Dana Farber Canc Inst, Dept Psychiat, Boston, MA 02115 USA. [Block, Susan] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Zivin, Kara] Univ Michigan, Sch Med, Vet Adm Med Ctr, Ann Arbor, MI 48109 USA. [Zivin, Kara] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Johnson, JG (reprint author), New York State Psychiat Inst & Hosp, Box 60,1051 Roverside Dr, New York, NY 10032 USA. EM jjohnso@pi.cpmc.columbia.edu FU NCI NIH HHS [R01 CA106370, CA106370]; NIA NIH HHS [P30 AG021342, P30AG21342]; NIMH NIH HHS [MH56529, R01 MH056529-03, MH63892, R01 MH056529, R01 MH063892-02, R01 MH063892] NR 29 TC 17 Z9 17 U1 1 U2 4 PU BRUNNER/MAZEL INC PI BRISTOL PA 1900 FROST RD, STE 101, BRISTOL, PA 19007-1598 USA SN 0748-1187 J9 DEATH STUD JI Death Stud. PY 2009 VL 33 IS 8 BP 691 EP 711 AR PII 913913241 DI 10.1080/07481180903070392 PG 21 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 483HT UT WOS:000268954600001 PM 19697482 ER PT B AU Hamilton, AR Mudgal, CS Jupiter, JB AF Hamilton, Abigail R. Mudgal, Chaitanya S. Jupiter, Jesse B. BE Wuisman, PIJ Smit, TH TI DEGRADABLE POLYMERS IN HAND SURGERY SO DEGRADABLE POLYMERS FOR SKELETAL IMPLANTS LA English DT Article; Book Chapter ID DISTAL RADIUS FRACTURES; BIOABSORBABLE OSTEOFIXATION DEVICES; INTERNAL-FIXATION; RHEUMATOID-ARTHRITIS; METACARPAL FRACTURES; OPEN REDUCTION; IMPLANTS; PLATE; ARTHRODESIS; SCREWS AB Implants used in the hand and wrist have to satisfy certain criteria. They should be small, biomechanically strong enough to withstand loading in the hand and wrist and should have a low profile. In addition to these features, it is extremely useful, if they are inert enough to avoid causing local soft tissue or bony reaction and therefore do not require additional procedures for removal. Bioabsorbable implants fulfill all these criteria, and although their use in the hand and wrist is still in its infancy, early data suggest that the rates of Success and complications associated with their use, are comparable to that associated with their metal counterparts. As costs associated with their production and use reduce, and more data regarding their efficacy become available, it appears that universal acceptance will follow. C1 [Mudgal, Chaitanya S.; Jupiter, Jesse B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Hamilton, Abigail R.] Massachusetts Gen Hosp, Harvard Combined Orthopaed Surg Residency Program, Boston, MA 02114 USA. [Hamilton, Abigail R.; Jupiter, Jesse B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr, Boston, MA 02114 USA. [Mudgal, Chaitanya S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org; jjupiter1@partners.org NR 47 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60692-426-6 PY 2009 BP 253 EP 266 PG 14 WC Engineering, Biomedical; Orthopedics; Polymer Science SC Engineering; Orthopedics; Polymer Science GA BMQ90 UT WOS:000273362600014 ER PT J AU Teng, E Tingus, KD Lu, PH Cummings, JL AF Teng, Edmond Tingus, Kathleen D. Lu, Po H. Cummings, Jeffrey L. TI Persistence of Neuropsychological Testing Deficits in Mild Cognitive Impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer disease; Memory; Cognition; Dementia; Psychometrics ID OSTERRIETH COMPLEX FIGURE; VASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; NORMATIVE DATA; CLINICAL SUBTYPES; MEMORY IMPAIRMENT; TEST-PERFORMANCE; OLDER-ADULTS; DEMENTIA; CONVERSION AB Background: The significant variability across studies of mild cognitive impairment (MCI) in rates of progression to Alzheimer's disease (AD) and reversion to normal cognition may be due to differences in specific neuropsychological tests and thresholds used to define MCI. Methods: We assessed 115 subjects with amnestic (AMN) or non-amnestic (NON) MCI on a standardized neuropsychological battery at baseline and after a mean follow-up of 16.4 months to determine the prevalence and persistence of deficits identified with specific tests. Results: The prevalence of impaired performance varied widely across tests. Deficits were more persistent in the AMN group than in the NON group. Baseline deficits in Visual Reproduction II and the California Verbal Learning Test were the best predictors of persistent memory impairment. Subjects who at baseline were impaired on multiple memory tests or had poorer overall memory performance were more likely to exhibit persistent memory deficits. Conclusions: The use of different neuropsychological tests and thresholds to diagnose MCI identified subsets of subjects with different rates of persistence of cognitive impairment. Standardization of the operational definition of cognitive impairment in MCI may result in more consistent predictions of progression to AD. Copyright (C) 2009 S. Karger AG, Basel C1 [Teng, Edmond; Tingus, Kathleen D.; Lu, Po H.; Cummings, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Cummings, Jeffrey L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit, Bldg 500 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU National Institute on Aging [P50 AG 16570]; Alzheimer's Disease Research Centers of California; Sidell-Kag an Foundation FX This research was supported by the National Institute on Aging (P50 AG 16570), the Alzheimer's Disease Research Centers of California, and the Sidell-Kag an Foundation. We would like to thank Charmaine Lowe, Myha Ngo, Alice Yau, and Michelle Zeller for their assistance with data management. NR 77 TC 19 Z9 20 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2009 VL 28 IS 2 BP 168 EP 178 DI 10.1159/000235732 PG 11 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 494DA UT WOS:000269788500010 PM 19707017 ER PT J AU Skoglund, L Ingvast, S Matsui, T Freeman, SH Frosch, MP Brundin, R Giedraitis, V Growdon, JH Hyman, BT Lannfelt, L Ingelsson, M Glaser, A AF Skoglund, Lena Ingvast, Sofie Matsui, Toshifumi Freeman, Stefanie H. Frosch, Matthew P. Brundin, Rosemarie Giedraitis, Vilmantas Growdon, John H. Hyman, Bradley T. Lannfelt, Lars Ingelsson, Martin Glaser, Anna TI No Evidence of PGRN or MAPT Gene Dosage Alterations in a Collection of Patients with Frontotemporal Lobar Degeneration SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Frontotemporal lobar degeneration; Frontotemporal dementia; Progranulin; Tau; Gene dosage alterations ID PROGRESSIVE SUPRANUCLEAR PALSY; TAU-GENE; PARKINSONS-DISEASE; LOCUS DUPLICATION; PROGRANULIN GENE; COMMON INVERSION; TRANSGENIC MICE; HUMAN GENOME; EXON 10; DEMENTIA AB Background/Aims: Alterations in gene dosage have recently been associated with neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, and deletions of the progranulin (PGRN) locus were recently described in patients with frontotemporal lobar degeneration (FTLD). FTLD is a genetically complex neurodegenerative disorder with mutations in the PGRN and the microtubule-associated protein tau (MAPT) genes being the most common known causes of familial FTLD. In this study, we investigated 39 patients with FTLD, previously found negative for mutations in PGRN and MAPT, for copy number alterations of these 2 genes. Methods: Gene dosage analysis of PGRN and MAPT was performed using multiplex ligation-dependent probe amplification. Results: We did not identify any PGRN or MAPT gene dosage variations in the 39 FTLD patients investigated. Conclusion: We therefore conclude that alterations in gene copy number of PGRN and MAPT are not a cause of disease in this collection of FTLD patients. Copyright (C) 2009 S. Karger AG, Basel C1 [Skoglund, Lena; Ingvast, Sofie; Brundin, Rosemarie; Giedraitis, Vilmantas; Lannfelt, Lars; Ingelsson, Martin; Glaser, Anna] Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden. [Matsui, Toshifumi; Freeman, Stefanie H.; Frosch, Matthew P.; Growdon, John H.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Skoglund, L (reprint author), Uppsala Univ, Dept Publ Hlth & Caring Sci, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden. EM Lena.Skoglund@pubcare.uu.se FU Swedish Research Council; Swedish Brain Foundation; Swedish Alzheimer Foundation; Swedish Dementia Association; Stohne's Foundation FX This work was supported by the Swedish Research Council, the Swedish Brain Foundation, the Swedish Alzheimer Foundation, the Swedish Dementia Association and Stohne's Foundation. NR 38 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2009 VL 28 IS 5 BP 471 EP 475 DI 10.1159/000260046 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 530QK UT WOS:000272607200012 PM 19940479 ER PT J AU Lesser, GT Haroutunian, V Purohit, DP Beeri, MS Schmeidler, J Honkanen, L Neufeld, R Libow, LS AF Lesser, Gerson T. Haroutunian, Vahram Purohit, Dushyant P. Beeri, Michal Schnaider Schmeidler, James Honkanen, Linda Neufeld, Richard Libow, Leslie S. TI Serum Lipids Are Related to Alzheimer's Pathology in Nursing Home Residents SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Lipids and dementia; Alzheimer's disease; Neuropathology of dementia; Nursing home; Cholesterol; Serum lipids ID DIFFERENT DIAGNOSTIC-CRITERIA; MILD COGNITIVE IMPAIRMENT; VASCULAR RISK-FACTORS; LATE-ONSET DEMENTIA; APOLIPOPROTEIN-E; DENSITY-LIPOPROTEIN; CHOLESTEROL LEVEL; NEURITIC PLAQUES; APOE GENOTYPE; OLDER PERSONS AB Background: Studies of associations between serum lipids and Alzheimer's disease ( AD) or other dementias in the elderly show conflicting results, perhaps due to misclassification of the various dementias. Methods: For 358 nursing home residents, serum lipids were studied at admission and diagnoses established at autopsy. We used defined neuropathological criteria to distinguish the presence of AD and to avoid errors of clinical dementia assessment. Results: Residents with any AD pathology, as compared to those without AD pathology, had higher mean serum total cholesterol (TC; 200.4 vs. 185.9 mg/dl; p = 0.02) and higher mean low-density lipoprotein cholesterol (LDL; 124.5 vs. 111.5 mg/dl; p = 0.03). Further, mean TC, LDL and high-density lipoprotein cholesterol levels all increased progressively with increasing pathological certainty of AD ( p for trend = 0.001, 0.02 and 0.02). Conclusions: TC and LDL were significantly related to pathologically defined AD. If serum lipids have a role in the pathogenesis of AD, interventions may modify the course of disease. Copyright (c) 2009 S. Karger AG, Basel C1 [Lesser, Gerson T.; Honkanen, Linda; Neufeld, Richard; Libow, Leslie S.] Jewish Home & Hosp, New York, NY 10025 USA. [Lesser, Gerson T.; Neufeld, Richard; Libow, Leslie S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Haroutunian, Vahram; Beeri, Michal Schnaider; Schmeidler, James] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Purohit, Dushyant P.] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Haroutunian, Vahram] Bronx Vet Affairs Med Ctr, New York, NY USA. RP Lesser, GT (reprint author), Jewish Home & Hosp, 120 W 106th St, New York, NY 10025 USA. EM glesser@jhha.org FU Dextra Baldwin McGonagle Foundation; NIA [AG02219]; NIH [M01-RR-00071] FX This work was supported by the Dextra Baldwin McGonagle Foundation, Joseph E. and Norma G. Saul Foundation, NIA grant AG02219 and NIH grant M01-RR-00071. NR 63 TC 22 Z9 23 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2009 VL 27 IS 1 BP 42 EP 49 DI 10.1159/000189268 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 400WD UT WOS:000262899200006 PM 19129700 ER PT J AU Carrion-Baralt, JR Melendez-Cabrero, J Beeri, MS Sano, M Silverman, JM AF Carrion-Baralt, Jose R. Melendez-Cabrero, Josefina Beeri, Michal Schnaider Sano, Mary Silverman, Jeremy M. TI The Neuropsychological Performance of Nondemented Puerto Rican Nonagenarians SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Successful cognitive aging; Puerto Rican nonagenarians; Oldest old population ID BOSTON NAMING TEST; AFRICAN-AMERICANS; ALZHEIMER-DISEASE; BATTERY; CERAD; NORMS; UTILITY; ELDERS; ADULTS; TRAIL AB Background/Aims: While the oldest old are the fastest growing segment of the US population, normative neuropsychological data for nondemented oldest old Spanish speakers are nonexistent. This study sought to evaluate the neuropsychological performance of nondemented nonagenarians residing in Puerto Rico and to compare their results with those of a similar English-speaking sample from New York. Methods: We studied 81 subjects who had a complete CERAD neuropsychological assessment in Spanish. We used multiple regression analysis to predict performance on the CERAD battery and ANCOVA to compare the Puerto Rico and New York samples. Results: In 10 out of the 13 neuropsychological tests administered, education was a significant predictor of performance. There were significant differences between the Puerto Rico and New York groups only in the Trail Making Tests. Conclusions: In this Puerto Rican sample, education was the strongest predictor of neuropsychological performance, which is consistent with previous studies. When education level is properly accounted for, the performance of Puerto Rican nonagenarians in the CERAD battery does not differ from the performance of US English-speaking nonagenarians. Copyright (c) 2009 S. Karger AG, Basel C1 [Carrion-Baralt, Jose R.] San Juan VA Med Ctr, Res & Dev Serv 151, San Juan, PR 00921 USA. [Carrion-Baralt, Jose R.; Melendez-Cabrero, Josefina; Beeri, Michal Schnaider; Sano, Mary; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sano, Mary; Silverman, Jeremy M.] James J Peters Bronx Veteran Affairs Med Ctr, Bronx, NY USA. RP Carrion-Baralt, JR (reprint author), San Juan VA Med Ctr, Res & Dev Serv 151, 10 Casia St, San Juan, PR 00921 USA. EM jose.carrion-baralt@mssm.edu FU NIA [1 K01 AG025203, 1 K01 AG023515, P50-AG05138, P01-AG02219]; US Alzheimer's Association grants FX This research was supported by NIA grants 1 K01 AG025203 (for J.R.C.-B.), 1 K01 AG023515 (for M. S. B.), P50-AG05138 (for M. S.), project 4 in P01-AG02219 (for J.M.S.) and two US Alzheimer's Association grants (for J.R.C.-B. and J.M.S.). NR 24 TC 5 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2009 VL 27 IS 4 BP 353 EP 360 DI 10.1159/000209213 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 428SQ UT WOS:000264870500008 PM 19293568 ER PT J AU Gleason, CE Gangnon, RE Fischer, BL Mahoney, JE AF Gleason, Carey E. Gangnon, Ronald E. Fischer, Barbara L. Mahoney, Jane E. TI Increased Risk for Falling Associated with Subtle Cognitive Impairment: Secondary Analysis of a Randomized Clinical Trial SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Accidental falls; Falls; Mini Mental State Exam; Cognition; Geriatrics; Older adults; Risk factors ID COMMUNITY; DEMENTIA; GAIT; SELECTION; PEOPLE; ADULTS AB Background/Aims: Having dementia increases patients' risk for accidental falls. However, it is unknown if having mild cognitive deficits also elevates a person's risk for falls. This study sought to clarify the relationship between subtle cognitive impairment, measured with a widely-used, clinic-based assessment, the Mini Mental State Exam (MMSE), and risk for falls. Methods: In a secondary analysis of the Kenosha County Falls Prevention Study, a randomized controlled trial targeting older adults at risk for falls, we examined the association between baseline MMSE and prospective rate of falls over 12 months in 172 subjects randomized to control group. Results: Using univariate analysis, the rate of falls increased with each unit decrease in MMSE score down to at least 22 (rate ratio 1.25, 95% confidence interval (CI) 1.09-1.45, p = 0.0026). Using stepwise multivariate regression, controlling for ability to perform activities of daily living, use of assistive device, current exercise, and arthritis, the association between MMSE score and falls rate persisted ( rate ratio 1.20, 95% CI 1.03-1.40, p = 0.021). Conclusion: Minimal decrements on the MMSE were associated with elevations in rate of falls, suggesting that subtle cognitive deficits reflected in MMSE scores above a cut-off consistent with a diagnosis of dementia, can influence risk for falls. Copyright (C) 2009 S. Karger AG, Basel C1 [Gleason, Carey E.; Mahoney, Jane E.] Univ Wisconsin, Dept Med, Sect Geriatr & Gerontol, Madison, WI 53705 USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Biostat, Madison, WI 53705 USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Med Informat, Madison, WI 53705 USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53705 USA. [Fischer, Barbara L.] William S Middleton Mem Vet Adm Med Ctr, Mental Hlth Serv, Madison, WI USA. [Gleason, Carey E.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. RP Gleason, CE (reprint author), Univ Wisconsin, Dept Med, Sect Geriatr, Madison VA GRECC, Room D4211,2500 Overlook Terrace, Madison, WI 53705 USA. EM ceg@medicine.wisc.edu FU NIH-NIA [K23 AG024302]; Kenosha County Multi-Factorial Falls Prevention Program for Older Adults; Wisconsin Family Care Aging and/or Disability Resource Center Prevention; Wm. S. Middleton Memorial VA, Madison, Wisc FX This work was supported by NIH-NIA grant K23 AG024302 (PI: C.E.G.), the Kenosha County Multi-Factorial Falls Prevention Program for Older Adults; A Wisconsin Family Care Aging and/or Disability Resource Center Prevention Funding Grant (PI: J.E.M.); and the Geriatric Research, Education and Clinical Center and Mental Health Service of the Wm. S. Middleton Memorial VA, Madison, Wisc. This is GRECC Manuscript Number: 2007-015. NR 24 TC 35 Z9 38 U1 0 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2009 VL 27 IS 6 BP 557 EP 563 DI 10.1159/000228257 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 485XY UT WOS:000269160500010 PM 19602883 ER PT J AU Schalock, PC AF Schalock, Peter C. TI Lichen Extracts SO DERMATITIS LA English DT Article ID ALLERGIC CONTACT-DERMATITIS; ACID AB Lichen-derived additives to commercial products are becoming a more frequent cause of allergic contact dermatitis. The most common lichen-derived additives are usnic acid and oak moss absolute. Both are useful for screening patients using "natural" or "botanical" products that may contain lichen-derived additives. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Schalock, PC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. NR 7 TC 2 Z9 2 U1 1 U2 2 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1710-3568 J9 DERMATITIS JI Dermatitis PD JAN-FEB PY 2009 VL 20 IS 1 BP 53 EP 54 DI 10.2310/6620.2008.08033 PG 2 WC Dermatology SC Dermatology GA 414SC UT WOS:000263884500009 PM 19321121 ER PT J AU Jambusaria-Pahlajani, A Schmults, CD Miller, CJ Shin, D Williams, J Kurd, SK Gelfand, JM AF Jambusaria-Pahlajani, Anokhi Schmults, Chrysalyne D. Miller, Christopher J. Shin, Daniel Williams, Jennifer Kurd, Shanu K. Gelfand, Joel M. TI Test Characteristics of High-Resolution Ultrasound in the Preoperative Assessment of Margins of Basal Cell and Squamous Cell Carcinoma in Patients Undergoing Mohs Micrographic Surgery SO DERMATOLOGIC SURGERY LA English DT Article ID NONMELANOMA SKIN-CANCER; COST AB Noninvasive techniques to assess subclinical spread of nonmelanoma skin cancer (NMSC) may improve surgical precision. High-resolution ultrasound has shown promise in evaluating the extent of NMSC. To determine the accuracy of high-resolution ultrasound to assess the margins of basal cell (BCC) and squamous cell carcinomas (SCC) before Mohs micrographic surgery (MMS). We enrolled 100 patients with invasive SCC or BCC. Before the first stage of MMS, a Mohs surgeon delineated the intended surgical margin. Subsequently, a trained ultrasound technologist independently evaluated disease extent using the EPISCAN I-200 to evaluate tumor extent beyond this margin. The accuracy of high-resolution ultrasound was subsequently tested by comparison with pathology from frozen sections. The test characteristics of the high-resolution ultrasound were sensitivity=32%, specificity=88%, positive predictive value=47%, and negative predictive value=79%. Subgroup analyses demonstrated better test characteristics for tumors larger than the median (area > 1.74 cm(2)). Qualitative analyses showed that high-resolution ultrasound was less likely to identify extension from tumors with subtle areas of extension, such as small foci of dermal invasion from infiltrative SCC and micronodular BCC. High-resolution ultrasound requires additional refinements to improve the preoperative determination of tumor extent before surgical treatment of NMSC. Longport, Inc., provided the ultrasound device for this study. Dr. Schmults, Dr. Gelfand, and Jennifer Williams received partial salary support from Longport during the study. C1 [Schmults, Chrysalyne D.] Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, Jamaica Plain, MA USA. [Jambusaria-Pahlajani, Anokhi; Miller, Christopher J.; Shin, Daniel; Williams, Jennifer; Kurd, Shanu K.; Gelfand, Joel M.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Jambusaria-Pahlajani, Anokhi; Schmults, Chrysalyne D.; Kurd, Shanu K.; Gelfand, Joel M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Gelfand, JM (reprint author), Hosp Univ Penn, Dept Dermatol, 2 Maloney Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM Joel.Gelfand@uphs.upenn.edu FU NIAMS NIH HHS [K23 AR051125] NR 12 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JAN PY 2009 VL 35 IS 1 BP 9 EP 16 DI 10.1111/j.1524-4725.2008.34376.x PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 391HH UT WOS:000262223900002 PM 19018815 ER PT J AU Lima, XT Seidler, EM Lima, HC Kimball, AB AF Lima, Xinaida T. Seidler, Elizabeth M. Lima, Hermenio C. Kimball, Alexandra B. TI Long-term safety of biologics in dermatology SO DERMATOLOGIC THERAPY LA English DT Review DE biologics; dermatology; long-term; safety ID TUMOR-NECROSIS-FACTOR; INTRAVENOUS IMMUNOGLOBULIN THERAPY; SEVERE PLAQUE PSORIASIS; OF-THE-LITERATURE; RECURRENT SPONTANEOUS-ABORTION; RANDOMIZED CONTROLLED-TRIALS; INFLAMMATORY-BOWEL-DISEASE; FACTOR-ALPHA ANTAGONISTS; VERSUS-HOST-DISEASE; RHEUMATOID-ARTHRITIS AB The use of biologics in dermatology has increased rapidly. Although most are relatively safe when correctly used and monitored, there are known side effects and adverse events that occur. Selection of patients should be done on a case-by-case basis. Severity of disease, comorbidity profile, drug profile, and cost-effectiveness should be all taken into consideration while deciding to start and/or maintain one of these therapies. Dermatologists should be aware of the benefits and limitations of this class of drugs, as well as the appropriate monitoring. The authors propose a concise overview of the safety profiles of some of the biologics currently used in the dermatologic field. C1 [Lima, Xinaida T.; Seidler, Elizabeth M.; Lima, Hermenio C.; Kimball, Alexandra B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Kimball, AB (reprint author), 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM akimball@partners.org RI Lima, Hermenio/G-5379-2010 OI Lima, Hermenio/0000-0003-0950-3731 FU Centocor FX Lima's salary as a research fellow is funded by a grant from Centocor. Dr. H. C. Lima is a consultant and speaker for Amgen (Wyeth) in Brazil. NR 178 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD JAN-FEB PY 2009 VL 22 IS 1 BP 2 EP 21 DI 10.1111/j.1529-8019.2008.01212.x PG 20 WC Dermatology SC Dermatology GA 408QZ UT WOS:000263451100002 PM 19222513 ER PT J AU Mehta, M Salas, AH Fay, A AF Mehta, Manisha Salas, Adriana Hernandez Fay, Aaron TI Trigeminal Dermatome Distribution in Patients with Glaucoma and Facial Port Wine Stain SO DERMATOLOGY LA English DT Article DE Port wine stain; Glaucoma; Trigeminal nerve; Nevus flammeus ID STURGE-WEBER SYNDROME; HEMANGIOMAS; MANIFESTATIONS AB Purpose: The importance of glaucoma screening in patients with upper eyelid involvement of facial port wine stain (PWS) is well known. This study questions the validity of this concept and reports the cutaneous patterns of PWS in 66 patients known to have glaucoma. Methods: Clinical records of 66 patients with glaucoma were reviewed, and the pattern of facial PWS involvement of the dermatomes of the trigeminal nerve was catalogued. The Pearson chi(2) test was applied. The literature supporting previous conclusions was reviewed. Results: 39 cases had ipsilateral and 27 had bilateral PWS; 9.3% had isolated ophthalmic branch (V(1)) involvement, 30.2% had ophthalmic and maxillary branch (V(1)V(2)) involvement, 5.8% had maxillary and mandibular branch (V(2)V(3)) involvement, and 52.3% had all 3 branches (V(1)V(2)V(3)) involved. Conclusions: Patients demonstrated to have glaucoma and facial PWS are approximately 7 times more likely to have multiple dermatomes of the trigeminal nerve involved (88.3%) in contrast to isolated V(1) involvement (9.3%). PWS patterns did not correlate with embryological segments of facial development. A review of the relevant literature resolves conflicting concepts and emphasizes the importance of glaucoma screening in all patients with trigeminal dermatome involvement of the PWS. Copyright (C) 2009 S. Karger AG, Basel C1 [Mehta, Manisha; Salas, Adriana Hernandez; Fay, Aaron] Massachusetts Eye & Ear Infirm, Eye Plast & Reconstruct Surg Div, Boston, MA 02114 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, Eye Plast & Reconstruct Surg Div, 243,Charles St, Boston, MA 02114 USA. EM afay@meei.harvard.edu NR 16 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2009 VL 219 IS 3 BP 219 EP 224 DI 10.1159/000235546 PG 6 WC Dermatology SC Dermatology GA 511FA UT WOS:000271148100005 PM 19672053 ER PT J AU Oberholzer, PA Cozzio, A Dummer, R French, LE Hofbauer, GFL AF Oberholzer, Patrick A. Cozzio, Antonio Dummer, Reinhard French, Lars E. Hofbauer, Guenther F. L. TI Granulomatous Slack Skin Responds to UVA1 Phototherapy SO DERMATOLOGY LA English DT Article DE Granulomatous slack skin; Cutaneous T cell lymphoma; Ultraviolet A1 phototherapy ID STAGE MYCOSIS-FUNGOIDES; T-CELL LYMPHOMA; HIGH-DOSE UVA1; ATOPIC-DERMATITIS; CUTANEOUS LYMPHOMAS; ULTRAVIOLET; THERAPY; EORTC; UVB; NM AB Granulomatous slack skin (GSS) is an extremely rare disorder within the group of cutaneous T cell lymphomas (CTCL). Ultraviolet A1 (UVA1) phototherapy has previously been reported to be useful in the treatment of CTCL such as mycosis fungoides. We report a 35-year-old Caucasian male with GSS treated with UVA1 phototherapy starting at 20 J/cm(2) UVA1 3 times a week and subsequently increased in increments of 5 J/cm(2) to a medium-range dose of 50 J/cm(2) per session. The patient underwent a total of 45 sessions with a cumulative dose of 1,495 J/cm(2) UVA1 without any adverse events. At the conclusion of UVA1 phototherapy, a decrease in erythema and skin thickness was observed which was most prominent in the periphery of the lesion in the right groin area. A follow-up 12 months after phototherapy showed continued treatment benefit. To our knowledge, this is the first report describing the successful use of UVA1 (340-400 nm) phototherapy in a patient with GSS. Copyright (C) 2009 S. Karger AG, Basel C1 [Oberholzer, Patrick A.; Cozzio, Antonio; Dummer, Reinhard; French, Lars E.; Hofbauer, Guenther F. L.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Oberholzer, Patrick A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Oberholzer, Patrick A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hofbauer, GFL (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. EM hofbauer@usz.ch RI Hofbauer, Gunther/B-2671-2010 OI Hofbauer, Gunther/0000-0003-0542-7989 NR 29 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2009 VL 219 IS 3 BP 268 EP 271 DI 10.1159/000226135 PG 4 WC Dermatology SC Dermatology GA 511FA UT WOS:000271148100012 PM 19546523 ER PT J AU Walters, KB Dodd, ME Mathias, JR Gallagher, AJ Bennin, DA Rhodes, J Kanki, JP Look, AT Grinblat, Y Huttenlocher, A AF Walters, Kevin B. Dodd, M. Ernest Mathias, Jonathan R. Gallagher, Andrea J. Bennin, David A. Rhodes, Jennifer Kanki, John P. Look, A. Thomas Grinblat, Yevgenya Huttenlocher, Anna TI Muscle Degeneration and Leukocyte Infiltration Caused by Mutation of Zebrafish Fad24 SO DEVELOPMENTAL DYNAMICS LA English DT Article DE zebrafish; fad24; neutrophil; inflammation ID SKELETAL-MUSCLE; MUSCULAR-DYSTROPHY; EARLY MACROPHAGES; DANIO-RERIO; MODEL HOST; IN-SITU; GENE; IDENTIFICATION; NEUTROPHILS; EXPRESSION AB Factor for adipocyte differentiation 24 (fad24) is a novel gene that has been implicated in adipocyte differentiation and DNA replication. In a screen for zebrafish mutants that have an abnormal tissue distribution of neutrophils, we identified an insertional allele of fad24, fad24(hi1019). Homozygous fad24(hi1019) larvae exhibit muscle degeneration accompanied by leukocyte infiltration. Muscle degeneration was extensive and included tissue apoptosis and disorganized, poorly striated muscle fibers. Blocking apoptosis using pan-caspase inhibitors resulted in decreased neutrophil recruitment into the body of the larva, suggesting a causative link between apoptosis and leukocyte infiltration. These findings suggest that zebrafish is a powerful genetic model system to address the interplay between muscle degeneration and leukocyte infiltration, and indicate that tissue apoptosis may contribute to neutrophil recruitment in some inflammatory states. Developmental Dynamics 238:86-99, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Walters, Kevin B.; Huttenlocher, Anna] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI USA. [Walters, Kevin B.; Dodd, M. Ernest; Mathias, Jonathan R.; Gallagher, Andrea J.; Bennin, David A.; Huttenlocher, Anna] Univ Wisconsin, Dept Pediat & Med Microbiol & Immunol, Madison, WI USA. [Rhodes, Jennifer; Kanki, John P.; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Grinblat, Yevgenya] Univ Wisconsin, Dept Zool, Madison, WI 53706 USA. [Grinblat, Yevgenya] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA. RP Huttenlocher, A (reprint author), 4205 Microbial Sci Bldg,1550 Linden Dr, Madison, WI 53706 USA. EM huttenlocher@wisc.edu FU NIH [RO1 GM074827, 5KO1DK69672, RR15402-01, RO1 GM076244-1]; Arthritis Foundation FX Grant sponsor: NIH; Grant numbers: RO1 GM074827, 5KO1DK69672, RR15402-01, RO1 GM076244-1; Grant. sponsor: Arthritis Foundation. NR 58 TC 21 Z9 21 U1 0 U2 2 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 JAN PY 2009 VL 238 IS 1 BP 86 EP 99 DI 10.1002/dvdy.21821 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 394PM UT WOS:000262459500009 PM 19097072 ER PT J AU Bortfeld, H Fava, E Boas, DA AF Bortfeld, Heather Fava, Eswen Boas, David A. TI Identifying Cortical Lateralization of Speech Processing in Infants Using Near-Infrared Spectroscopy SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID BLOOD OXYGENATION CHANGES; EVENT-RELATED FMRI; BRAIN ACTIVATION; NEWBORN-INFANTS; AUDITORY-CORTEX; HEMODYNAMIC-RESPONSE; OPTICAL TOPOGRAPHY; LANGUAGE FUNCTIONS; FRONTAL-LOBE; STIMULATION AB We investigate the utility of near-infrared spectroscopy (NIRS) as an alternative technique for studying infant speech processing. NIRS is an optical imaging technology that uses relative changes in total hemoglobin concentration and oxygenation as an indicator of neural activation. Procedurally, NIRS has the advantage over more common methods (e.g., fMRI) in that it can be used to study the neural responses of behaviorally active infants. Older infants (aged 6-9 months) were allowed to sit on their caretakers' laps during stimulus presentation to determine relative differences in focal activity in the temporal region of the brain during speech processing. Results revealed a dissociation of sensory-specific processing in two cortical regions, the left and right temporal lobes. These findings are consistent with those obtained using other neurophysiological methods and point to the utility of NIRS as a means of establishing neural correlates of language development in older (and more active) infants. C1 [Bortfeld, Heather; Fava, Eswen] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Boas, David A.] Harvard Univ, Sch Med, Anthinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA USA. RP Bortfeld, H (reprint author), Texas A&M Univ, Dept Psychol, 4235 TAMU, College Stn, TX 77843 USA. EM hbortfeld@psych.tamu.edu OI Bortfeld, Heather/0000-0002-3545-5449 FU James S. McDonnell Foundation; [HD046533]; [P41-RR14075] FX This research was supported by grants from the James S. McDonnell Foundation 21st Century Research Award, Bridging Brain, Mind, and Behavior and from HD046533 to Heather Bortfeld and P41-RR14075 to David Boas. NR 56 TC 39 Z9 41 U1 2 U2 6 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2009 VL 34 IS 1 BP 52 EP 65 AR PII 907761921 DI 10.1080/87565640802564481 PG 14 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 398FD UT WOS:000262717100003 PM 19142766 ER PT J AU Makris, N Biederman, J Monuteaux, MC Seidman, LJ AF Makris, Nikos Biederman, Joseph Monuteaux, Michael C. Seidman, Larry J. TI Towards Conceptualizing a Neural Systems-Based Anatomy of Attention-Deficit/Hyperactivity Disorder SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE Attention-deficit/hyperactivity disorder; Magnetic resonance imaging; Diffusion tensor imaging; Neural systems; Executive function; Attention; Impulsivity; Neuroanatomy ID DEFICIT-HYPERACTIVITY DISORDER; ANTERIOR CINGULATE CORTEX; ABNORMAL-PSYCHICAL-CONDITIONS; COMORBIDITY SURVEY REPLICATION; COGNITIVE-AFFECTIVE SYNDROME; RIGHT-HEMISPHERE DOMINANCE; CORPUS-CALLOSUM; RHESUS-MONKEY; BASAL GANGLIA; WHITE-MATTER AB Convergent data from neuroimaging, neuropsychological, genetic and neurochemical studies in attention-deficit/hyperactivity disorder (ADHD) have implicated dysfunction of the dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC), which form the cortical arm of the frontostriatal network supporting executive functions. Furthermore, besides the DLPFC and dACC, structural and functional imaging studies have shown abnormalities in key brain regions within distributed cortical networks supporting attention. The conceptualization of neural systems biology in ADHD aims at the understanding of what organizing principles have been altered during development within the brain of a person with ADHD. Characterizing these neural systems using neuroimaging could be critical for the description of structural endophenotypes, and may provide the capability of in vivo categorization and correlation with behavior and genes. Copyright (C) 2009 S. Karger AG, Basel C1 [Makris, Nikos] Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr,Publ Psychiat Div, Boston, MA 02115 USA. [Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02115 USA. [Makris, Nikos] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Makris, N (reprint author), Massachusetts Gen Hosp, Ctr Morphometr Anal, 149 13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu FU National Institutes of Mental Health [MH 62152]; The National Association for Research in Schizophrenia and Depression; National Institutes of Health National Center for Complementary and Alternative Medicine [PO1AT00204805]; National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award; Janssen Pharmaceuticals; Johnson; Johnson Center for the Study of Psychopathology; Fairway Trust; The National Center for Research Resources [P41RR14075]; March of Dimes Foundation; Mental Illness and Neuroscience Discovery Institute FX This work was primarily supported by a grant from the National Institutes of Mental Health, No. MH 62152 (L. J. S.). Preparation of this article was also supported in part by grants from: The National Association for Research in Schizophrenia and Depression and the National Institutes of Health National Center for Complementary and Alternative Medicine, No. PO1AT00204805 (N. M.); the National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award (J. B.), Janssen Pharmaceuticals and the Johnson and Johnson Center for the Study of Psychopathology (J. B.); the Fairway Trust (D. K.); The National Center for Research Resources, No. P41RR14075; the March of Dimes Foundation (L. J. S.), and the Mental Illness and Neuroscience Discovery Institute (L. J. S.). NR 178 TC 72 Z9 72 U1 7 U2 26 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2009 VL 31 IS 1-2 BP 36 EP 49 DI 10.1159/000207492 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 436MJ UT WOS:000265417900005 PM 19372685 ER PT J AU Malanga, CJ Ren, JQ Guerriero, RM Kosofsky, BE AF Malanga, C. J. Ren, Jia-Qian Guerriero, Rejean M. Kosofsky, Barry E. TI Augmentation of Cocaine-Sensitized Dopamine Release in the Nucleus Accumbens of Adult Mice following Prenatal Cocaine Exposure SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE Gestation; Cocaine exposure, in utero; Microdialysis, in vivo; Sensitization; Drug abuse; Withdrawal ID CONDITIONED PLACE-PREFERENCE; VENTRAL TEGMENTAL AREA; IN-VIVO MICRODIALYSIS; EXTRACELLULAR DOPAMINE; BEHAVIORAL SENSITIZATION; TYROSINE-HYDROXYLASE; RAT STRIATUM; TIME-COURSE; DORSOLATERAL STRIATUM; GESTATIONAL COCAINE AB Behavioral changes in adult mice after prenatal exposure to cocaine have been identified. Mice exposed to cocaine in utero (40 or 20 mg/kg/day) and controls were given a sensitizing cocaine regimen (15 mg/kg every other day ! 7 doses), withdrawn for 21 days, and challenged with 15 mg/kg cocaine. In vivo microdialysis for dopamine (DA), serotonin, and their metabolites in awake behaving mice on the first, seventh and challenge doses showed increased cocaine-stimulated DA release in the nucleus accumbens, which was significantly enhanced after prenatal cocaine exposure. This effect was not due to fetal malnutrition or changes in the total tissue DA content. Early developmental cocaine exposure may alter adaptation of brain reward systems to chronic psychostimulant exposure in adulthood. Copyright (C) 2009 S. Karger AG, Basel C1 [Malanga, C. J.; Ren, Jia-Qian; Guerriero, Rejean M.; Kosofsky, Barry E.] Massachusetts Gen Hosp, Dept Neurol, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. RP Malanga, CJ (reprint author), Univ N Carolina, Sch Med, Dept Neurol, Phys Off Bldg,170 Manning Dr,CB 7025, Chapel Hill, NC 27599 USA. EM malangacj@neurology.unc.edu OI Malanga, C.J./0000-0003-4808-3995 FU National Institute on Drug Abuse [DA015429, DA000354, DA008648]; William Randolph Hearst Fund of the Harvard Medical School FX The authors are grateful to Dr. Anjali Rajadyaksha for her helpful comments in the preparation of the manuscript. This work was supported by grants DA015429 (C. J. M.), DA000354 (B. E. K.), DA008648 (B. E. K.) from the National Institute on Drug Abuse, and an award from the William Randolph Hearst Fund of the Harvard Medical School (C. J. M.). NR 110 TC 5 Z9 6 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2009 VL 31 IS 1-2 BP 76 EP 89 DI 10.1159/000207496 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 436MJ UT WOS:000265417900009 PM 19372689 ER PT J AU Vexler, ZS Yenari, MA AF Vexler, Zinaida S. Yenari, Midori A. TI Does Inflammation after Stroke Affect the Developing Brain Differently than Adult Brain? SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT 6th Hershey Conference on Developmental Brain Injury CY JUN 04-07, 2008 CL Ecquevilly, FRANCE SP Natl Inst Neurolog Disorders & Stroke DE Stroke; Hypoxia-ischemia; Cytokine; Chemokine; Microglia; Neuroprotection; Neurogenesis ID FOCAL CEREBRAL-ISCHEMIA; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MONOCYTE CHEMOATTRACTANT PROTEIN-1; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; INTERLEUKIN-1 RECEPTOR ANTAGONIST; SUBVENTRICULAR ZONE NEUROGENESIS; NEONATAL HYPOXIA-ISCHEMIA; LONG-TERM NEUROPROTECTION AB The immature brain is prone to hypoxic-ischemic encephalopathy and stroke. The incidence of arterial stroke in newborns is similar to that in the elderly. However, the pathogenesis of ischemic brain injury is profoundly affected by age at the time of the insult. Necrosis is a dominant type of neuronal cell death in adult brain, whereas widespread neuronal apoptosis is unique for the early postnatal synaptogenesis period. The inflammatory response, in conjunction with excitotoxic and oxidative responses, is the major contributor to ischemic injury in both the immature and adult brain, but there are several areas where these responses diverge. We discuss the contribution of various inflammatory mechanisms to injury and repair after cerebral ischemia in the context of CNS immaturity. In particular, we discuss the role of lower expression of selectins, a more limited leukocyte transmigration, undeveloped complement pathways, a more rapid microglial activation, differences in cytokine and chemokine interplay, and a different threshold to oxidative stress in the immature brain. We also discuss differences in activation of intracellular pathways, especially nuclear factor kappa B and mitogen-activated protein kinases. Finally, we discuss emerging data on both the supportive and adverse roles of inflammation in plasticity and repair after stroke. Copyright (C) 2009 S. Karger AG, Basel C1 [Vexler, Zinaida S.; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Vexler, ZS (reprint author), Univ Calif San Francisco, Dept Neurol, 521 Parnassus Ave,C215, San Francisco, CA 94143 USA. EM Zena.Vexler@ucsf.edu FU NINDS NIH HHS [R01 NS040516, R01 NS044025, R01 NS40516, R01 NS44025] NR 222 TC 65 Z9 66 U1 1 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2009 VL 31 IS 5 BP 378 EP 393 DI 10.1159/000232556 PG 16 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 491JH UT WOS:000269574200002 PM 19672067 ER PT J AU Lieb, W Pencina, MJ Lanier, KJ Tofler, GH Levy, D Fox, CS Wang, TJ D'Agostino, RB Vasan, RS AF Lieb, Wolfgang Pencina, Michael J. Lanier, Katherine J. Tofler, Geoffrey H. Levy, Daniel Fox, Caroline S. Wang, Thomas J. D'Agostino, Ralph B., Sr. Vasan, Ramachandran S. TI Association of Parental Obesity With Concentrations of Select Systemic Biomarkers in Nonobese Offspring The Framingham Heart Study SO DIABETES LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; C-REACTIVE PROTEIN; INSULIN-RESISTANCE ATHEROSCLEROSIS; NATRIURETIC PEPTIDE LEVELS; METABOLIC-SYNDROME; OVERWEIGHT; FIBRINOGEN; CHILDREN; MARKERS; IMPACT AB OBJECTIVE-Parental obesity is a risk factor for offspring obesity. It is unclear whether parental obesity also confers risk for obesity-associated conditions (e.g., a proinflammatory or prothrombotic state) in the absence of offspring obesity. RESEARCH DESIGN AND METHODS-We compared concentrations of multiple biomarkers representing distinct biological pathways (C-reactive protein [CRP], aldosterone, renin, B-type natriuretic peptide, NH(2)-terminal proatrial natriuretic peptide, fibrinogen, and plasminogen activator inhibitor-1) in nonobese Framingham Offspring Study participants with no parents (n = 665), one parent (n = 488), or two parents (n 119) with obesity (BMI; >= 30 kg/m(2)). RESULTS-Nonobese offspring with both parents with obesity had higher CRP levels (median 2.16 mg/l) than offspring with one parent (1.58 mg/l) or no parents (1.35 mg/l) with obesity. After multivariable adjustment, a nonlinear relationship with parental obesity became evident: compared with those without parental obesity, CRP levels were higher in offspring with two obese parents (P = 0.04) but not in offspring with only one obese parent (P = 0.76). Renin levels were more linearly related to parental obesity status, being significantly higher in offspring with one parent (P = 0.04) or two parents (P = 0.09) with obesity (P = 0.02 for trend). The other systemic biomarkers did not vary according to parental obesity status (all P > 0.05). CONCLUSIONS-Our findings suggest that offspring with a high risk of developing obesity have an altered biomarker profile, characterized by systemic inflammation and increased neurohormonal activity, even in the absence of obesity. This is consistent with the notion that parental obesity may confer an increased susceptibility to other adiposity-associated traits. Diabetes 58: 134-137,2009 C1 [Lieb, Wolfgang; Pencina, Michael J.; Levy, Daniel; Fox, Caroline S.; Wang, Thomas J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Pencina, Michael J.; Lanier, Katherine J.; D'Agostino, Ralph B., Sr.] Boston Univ, Sch Med, Dept Math, Boston, MA 02118 USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia. [Levy, Daniel; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. EM vasan@bu.edu RI Lieb, Wolfgang/C-1990-2012; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24HL04334, K24 HL004334, N01-HC-25195, N01HC25195]; NIDDK NIH HHS [1R01-DK-080739, R01 DK080739] NR 24 TC 19 Z9 21 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 JAN PY 2009 VL 58 IS 1 BP 134 EP 137 DI 10.2337/db08-0918 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390TR UT WOS:000262187100023 PM 18931036 ER PT J AU Hisanaga, E Nagasawa, M Ueki, K Kulkarni, RN Mori, M Kojima, I AF Hisanaga, Etsuko Nagasawa, Masahiro Ueki, Kobjiro Kulkarni, Rohit N. Mori, Masatomo Kojima, Itaru TI Regulation of Calcium-Permeable TRPV2 Channel by Insulin in Pancreatic beta-Cells SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; CA2+-PERMEABLE CHANNEL; CATION CHANNEL; RECEPTOR; TRANSLOCATION; ACTIVATION; SECRETION; ISLETS AB OBJECTIVE-Calcium-permeable cation channel TRPV2 is expressed in pancreatic beta-cells. We investigated regulation and function of TRPV2 in beta-cells. RESEARCH DESIGN AND METHODS-Translocation of TRPV2 was assessed in MIN6 cells and cultured mouse beta-cells by transfecting TRPV2 fused to green fluorescent protein or TRPV2 containing c-Myc tag in the extracellular domain. Calcium entry was assessed by monitoring fura-2 fluorescence. RESULTS-In MIN6 cells, TRPV2 was observed mainly in cytoplasm in an unstimulated condition. Addition of exogenous insulin induced translocation and insertion of TRPV2 to the plasma membrane. Consistent with these observations, insulin increased calcium entry, which was inhibited by tranilast, an inhibitor of TRPV2, or by knockdown of TRPV2 using shRNA. A high concentration of glucose also induced translocation of TRPV2, which was blocked by nefedipine, diazoxide, and somatostatin, agents blocking glucose-induced insulin secretion. Knockdown of the insulin receptor attenuated insulin-induced translocation of TRPV2. Similarly, the effect of insulin on TRPV2 translocation was not observed in a beta-cell line derived from islets obtained from a beta-cell-specific insulin receptor knockout mouse. Knockdown of TRPV2 or addition of tranilast significantly inhibited insulin secretion induced by a high concentration of glucose. Likewise, cell growth induced by serum and glucose was inhibited by tranilast or by knockdown of TRPV2. Finally, insulin- induced translocation of TRPV2 was observed in cultured mouse P-cells, and knockdown of TRPV2 reduced insulin secretion induced by glucose. CONCLUSIONS-TRPV2 is regulated by insulin and is involved in the autocrine action of this hormone on beta-cells. Diabetes 58: 174-184, 2009 C1 [Hisanaga, Etsuko; Nagasawa, Masahiro; Ueki, Kobjiro; Kojima, Itaru] Gunma Univ, Inst Mol & Cellular Regulat, Maebashi, Gumma 371, Japan. [Hisanaga, Etsuko; Mori, Masatomo] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Maebashi, Gumma 371, Japan. [Ueki, Kobjiro] Univ Tokyo, Grad Sch Sci, Dept Metab Dis, Tokyo 113, Japan. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. RP Kojima, I (reprint author), Gunma Univ, Inst Mol & Cellular Regulat, Maebashi, Gumma 371, Japan. EM ikojima@showa.gunma-u.ac.jp FU Ministry of Science, Education, Sports and Culture of Japan; Global COE Program of Japan; NIH [RO1 DK67536] FX The authors are grateful to Mayumi Odagiri for secretarial assistance. NR 29 TC 54 Z9 56 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 JAN PY 2009 VL 58 IS 1 BP 174 EP 184 DI 10.2337/db08-0862 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390TR UT WOS:000262187100028 PM 18984736 ER PT J AU Arita, R Hata, Y Nakao, S Kita, T Miura, M Kawahara, S Zandi, S Almulki, L Tayyari, F Shimokawa, H Hafezi-Moghadam, A Ishibashi, T AF Arita, Ryoichi Hata, Yasuaki Nakao, Shintaro Kita, Takeshi Miura, Muneki Kawahara, Shuhei Zandi, Souska Almulki, Lama Tayyari, Faryan Shimokawa, Hiroaki Hafezi-Moghadam, Ali Ishibashi, Tatsuro TI Rho Kinase Inhibition by Fasudil Ameliorates Diabetes-Induced Microvascular Damage SO DIABETES LA English DT Article ID NITRIC-OXIDE SYNTHASE; INTERCELLULAR-ADHESION MOLECULE-1; AORTIC ENDOTHELIAL-CELLS; CORONARY-ARTERY SPASM; IN-VIVO; GLUCOSE CONTROL; ACTIVATION; EXPRESSION; DYSFUNCTION; RETINOPATHY AB OBJECTIVE-Leukocyte adhesion in retinal microvasuculature substantially contributes to diabetic retinopathy. Involvement of the Rho/Rho kinase (ROCK) pathway in diabetic microvasculopathy and therapeutic potential of fasudil, a selective ROCK inhibitor, are investigated. RESEARCH DESIGN AND METHODS-Localization of RhoA/ROCK and Rho activity were examined in retinal tissues of rats. Impact of intravitreal fasudil administration on retinal endothelial nitric oxide synthase (eNOS) and myosin phosphatase target protein (MYPT)-1 phosphorylation, intercellular adhesion molecule-1 (ICAM-1) expression, leukocyte adhesion, and endothelial damage in rat eyes were investigated. Adhesion of neutrophils from diabetic retinopathy patients or nondiabetic control subjects to cultured microvascular endothelial cells was quantified. The potential of fasudil for endothelial protection was investigated by measuring the number of adherent neutrophils and terminal transferase-mediated dUTP nick-end labeling-positive endothelial cells. RESULTS-RhoA and ROCK colocalized predominantly in retinal microvessels. Significant Rho activation was observed in retinas of diabetic rats. Intravitreal fasudil significantly increased eNOS phosphorylation, whereas it reduced MYPT-1 phosphorylation, ICAM-1 expression, leukocyte adhesion, and the number of damaged endothelium in retinas of diabetic rats. Neutrophils from diabetic retinopathy patients showed significantly higher adhesion to cultured endothelium and caused endothelial apoptosis, which was significantly reduced by fasudil. Blockade of the Fas-FasL interaction prevented endothelial apoptosis. The protective effect of fasudil on endothelial apoptosis was significantly reversed by N omega-nitro-L-arginine methyl ester, a NOS inhibitor, whereas neutrophil adhesion remained unaffected. CONCLUSIONS-The Rho/ROCK pathway plays a critical role in diabetic retinal microvasculopathy. Fasudil protects the vascular endothelium by inhibiting neutrophil adhesion and reducing neutrophil-induced endothelial injury. ROCK inhibition may become a new strategy in the management of diabetic retinopathy, especially in its early stages. Diabetes 58:215-227, 2009 C1 [Arita, Ryoichi; Hata, Yasuaki; Nakao, Shintaro; Kita, Takeshi; Miura, Muneki; Kawahara, Shuhei; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan. [Nakao, Shintaro; Zandi, Souska; Almulki, Lama; Tayyari, Faryan; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Shimokawa, Hiroaki] Tohoku Univ, Grad Sch Med, Dept Cardiol, Sendai, Miyagi 980, Japan. RP Hata, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan. EM hatachan@med.kyushu-u.ac.jp OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU Japan Eye Bank Association; Ministry of Education, Science, Sports and Culture, Japan [19592026]; National Institutes of Health [AI050775, HL086933]; National Eye Institute Core [EY14104]; Massachusetts Lions Eye Research Fund; Marion W. and Edward F. Knight Fund; Research to Prevent Blindness FX We also thank Yusuke Murakami, Ri-ichiro Kohno, and Takeru Yoshimura (Department of Ophthalmology, Kyushu University) for their technical support. We appreciate the technical support from the Research Support Center, Graduate School of Medical Sciences, Kyushu University. NR 50 TC 90 Z9 99 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2009 VL 58 IS 1 BP 215 EP 226 DI 10.2337/db08-0762 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390TR UT WOS:000262187100033 PM 18840783 ER PT J AU Sale, MM Lu, LY Spruill, IJ Fernandes, JK Lok, KH Divers, J Langefeld, CD Garvey, WT AF Sale, Michele M. Lu, Lingyi Spruill, Ida J. Fernandes, Jyotika K. Lok, Kerry H. Divers, Jasmin Langefeld, Carl D. Garvey, W. Timothy TI Genome-Wide Linkage Scan in Gullah-Speaking African American Families With Type 2 Diabetes The Sea Islands Genetic African American Registry (Project SuGAR) SO DIABETES LA English DT Article; Proceedings Paper CT 68th Annual Meeting of the American-Diabetes-Association CY JUN 06-10, 2008 CL San Francisco, CA SP Amer Diabet Assoc ID SINGLE NUCLEOTIDE POLYMORPHISMS; FACTOR-7-LIKE-2 TCF7L2 GENE; SUSCEPTIBILITY GENES; ASSOCIATION ANALYSIS; IDENTIFICATION; VARIANTS; MELLITUS; POPULATIONS; AFFINITIES; LOCUS AB OBJECTIVE-The Gullah-speaking African American population from the Sea Islands of South Carolina is characterized by a low degree of European admixture and high rates of type 2 diabetes and diabetic complications. Affected relative pairs with type 2 diabetes were recruited through the Sea Islands Genetic African American Registry (Project SuGAR). RESEARCH DESIGN AND METHODS-We conducted a genome-wide linkage scan, genotyping 5,974 single nucleotide polymorphisms in 471 affected subjects and 50 unaffected relatives from 197 pedigrees. Data were analyzed using a multipoint engine for rapid likelihood inference and ordered subsets analyses (OSAs) for age at type 2 diabetes diagnosis, waist circumference, waist-to-hip ratio, and BMI. We searched for heterogeneity and interactions using a conditional logistic regression likelihood approach. RESULTS-Linkage peaks on chromosome 14 at 123-124 cM were detected for type 2 diabetes (logarithm of odds [LOD] 2. 10) and for the subset with later age at type 2 diabetes diagnosis (maximum LOD 4.05). Two linkage peaks on chromosome 7 were detected at 44-45 cM for type 2 diabetes (LOD 1.18) and at 78 cM for type 2 diabetes (LOD 1.64) and the subset with earlier age at type 2 diabetes diagnosis (maximum LOD 3.93). The chromosome 14 locus and a peak on 7p at 29.5 cM were identified as important in the multilocus model. Other regions that provided modest evidence for linkage included chromosome 1 at 167.5 cM (LOD 1.51) and chromosome 3 at 121.0 cM (LOD 1.61). CONCLUSIONS-This study revealed a novel type 2 diabetes locus in an African American population on 14q that appears to reduce age of disease onset and confirmed two loci on chromosome 7. Diabetes 58:260-267, 2009 C1 [Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA. [Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Lu, Lingyi; Divers, Jasmin; Langefeld, Carl D.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Spruill, Ida J.; Fernandes, Jyotika K.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lok, Kerry H.; Garvey, W. Timothy] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. RP Sale, MM (reprint author), Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA. EM msale@virginia.edu FU NCRR NIH HHS [M01 RR001070, M01 RR007122, M01 RR007122-150269, M01-RR-1070, P20 RR017696, P20-RR-17696]; NHGRI NIH HHS [N01HG65403]; NIDDK NIH HHS [DK-66358, P30 DK056336, P30-DK-56336, R01 DK047461, R01 DK066358, R01 DK066358-01, R01 DK066358-02, R01 DK066358-03] NR 36 TC 16 Z9 16 U1 2 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2009 VL 58 IS 1 BP 260 EP 267 DI 10.2337/db08-0198 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390TR UT WOS:000262187100038 PM 18835935 ER PT J AU Coletta, DK Schneider, J Hu, SL Dyer, TD Puppala, S Farook, VS Arya, R Lehman, DM Blangero, J DeFronzo, RA Duggirala, R Jenkinson, CP AF Coletta, Dawn K. Schneider, Jennifer Hu, Shirley L. Dyer, Thomas D. Puppala, Sobha Farook, Vidya S. Arya, Rector Lehman, Donna M. Blangero, John DeFronzo, Ralph A. Duggirala, Ravindranath Jenkinson, Christopher P. TI Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study SO DIABETES LA English DT Article ID OLD ORDER AMISH; MEXICAN-AMERICANS; SUSCEPTIBILITY LOCUS; INSULIN-RESISTANCE; QUANTITATIVE TRAITS; ASSOCIATION; DISEASE; FAMILY; SEGREGATION; CHOLESTEROL AB OBJECTIVE-Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal. of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS-We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis. RESULTS-After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 +/- 7% (P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 X 10(-5)). This region on 12p harbors the gene-encoding adiponectin receptor 2 (AdipoR2), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES. CONCLUSIONS-Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans. Diabetes 58: 279-284, 2009 C1 [Coletta, Dawn K.; Hu, Shirley L.; DeFronzo, Ralph A.; Jenkinson, Christopher P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX 78229 USA. [Schneider, Jennifer; Dyer, Thomas D.; Puppala, Sobha; Farook, Vidya S.; Blangero, John; Duggirala, Ravindranath; Jenkinson, Christopher P.] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Arya, Rector; Lehman, Donna M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [DeFronzo, Ralph A.; Jenkinson, Christopher P.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Coletta, DK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX 78229 USA. EM dawn.coletta@asu.edu RI Coletta, Dawn/G-6382-2016; OI Coletta, Dawn/0000-0001-5819-5152 FU Veterans Administration Epidemiologic; National Institutes of Health [DK42273, DK47482, DK53889, DK70746]; American Heart Association National Scientist Development FX We thank Marcel J. Fourcaudot and Lenore M. Rodriguez for excellent technical assistance. We thank our nurses (James King, John Kincaid, Rose Kaminski-Graham, and Norma Diaz) for their excellent care of the patients throughout the study. We thank the participants of VAGES and are grateful for their participation and cooperation. NR 38 TC 12 Z9 13 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2009 VL 58 IS 1 BP 279 EP 284 DI 10.2337/db08-0491 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390TR UT WOS:000262187100041 PM 18931038 ER PT B AU Brennan, AM Sweeney, L Mantzoros, CS AF Brennan, Aoife M. Sweeney, Laura Mantzoros, Christos S. BE Regensteiner, JG Reusch, JEB Stewart, KJ Veves, A TI The Metabolic Syndrome SO DIABETES AND EXERCISE SE Contemporary Diabetes LA English DT Article; Book Chapter DE Obesity; Insulin resistance; Type 2 diabetes; Visceral obesity; Dyslipidemia; Cardiovascular disease; Hypertension; Proinflammatory state; Diagnosis; Epidemiology ID INTERNATIONAL-DIABETES-FEDERATION; NUTRITION EXAMINATION SURVEY; POLYCYSTIC-OVARY-SYNDROME; 3RD NATIONAL-HEALTH; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; VASCULAR REACTIVITY; UNITED-STATES; WEIGHT-LOSS AB The metabolic syndrome refers to the clustering of metabolic abnormalities more frequently than would be expected by chance alone. These metabolic abnormalities are all risk factors for cardiovascular disease (CVD), and the epidemiological association between these multiple risk factors points to the possibility of a unifying underlying pathophysiology. Obesity, in particular visceral adiposity, insulin resistance, and some degree of abnormal glucose metabolism coupled with dyslipidemia and abnormal blood pressure are the hallmarks of the syndrome. Epidemiological data correlates the presence of the metabolic syndrome with a proinflammatory state and greater risk for diabetes and CVD. There is also emerging evidence that the syndrome is associated with an increased risk of several malignancies. Since obesity is an increasing global burden, it is expected that the number of individuals with the metabolic syndrome will increase worldwide. An internationally accepted definition of the syndrome would facilitate both clinical diagnosis and future research to accurately assess risk and to identify preventative and therapeutic strategies. C1 [Brennan, Aoife M.; Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Internal Med, Boston, MA 02215 USA. [Brennan, Aoife M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Brennan, AM (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Internal Med, Boston, MA 02215 USA. NR 81 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-926-0 J9 CONTEMP DIABETES PY 2009 BP 69 EP 81 DI 10.1007/978-1-59745-260-1_3 D2 10.1007/978-1-59745-260-1 PG 13 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Medicine, General & Internal; Physiology; Sport Sciences SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; General & Internal Medicine; Physiology; Sport Sciences GA BJS87 UT WOS:000267119300003 ER PT B AU Doupis, J Schramm, JC Veves, A AF Doupis, John Schramm, Jordan C. Veves, Aristidis BE Regensteiner, JG Reusch, JEB Stewart, KJ Veves, A TI Endothelial Dysfunction Inflammation, and Exercise SO DIABETES AND EXERCISE SE Contemporary Diabetes LA English DT Article; Book Chapter DE Diabetes; Exersice; Endothelial Dysfunction ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; CHRONIC HEART-FAILURE; DEPENDENT DIABETES-MELLITUS; FUTURE CARDIOVASCULAR EVENTS; PERIPHERAL VASCULAR-DISEASE; ACUTE MYOCARDIAL-INFARCTION; IMPAIRED GLUCOSE-TOLERANCE; ADIPOSE-SPECIFIC PROTEIN; LOW-DENSITY-LIPOPROTEIN AB Vascular endothelial function is essential for the maintenance of health of the vessel wall and for the vasomotor control in both conduit and resistance vessels. These functions are due to the production of numerous vasomodulators, of which nitric oxide (NO) has been the most significant and the most widely studied. Endothelial function deteriorates with age and in the presence of several other risk factors for atherosclerosis, including diabetes, obesity, hypercholesterolemia, hypertension, hyperhomocysteinemia, and smoking. In addition, endothelial dysfunction is highly related with chronic vascular inflammation and is considered to be an independent risk factor for atherosclerosis. Physical training has beneficial effects on multiple cardiovascular risk factors, such as dyslipidemia, hypertension, diabetes, and cardiovascular events, by augmenting endothelial, NO-dependent vasodilation in both large and small arteries. In addition, physical activity shows beneficial effect on the chronic vascular inflammation, reducing most of the biochemical inflammation markers. C1 [Doupis, John] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Clin Res, Boston, MA 02115 USA. [Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Joslin Beth Israel Deaconess Foot Ctr, Microcirculat Lab,Dept Surg, Boston, MA 02215 USA. RP Doupis, J (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Clin Res, Boston, MA 02115 USA. OI Schramm, Jordan/0000-0002-0896-1071 NR 137 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-926-0 J9 CONTEMP DIABETES PY 2009 BP 131 EP 147 DI 10.1007/978-1-59745-260-1_6 D2 10.1007/978-1-59745-260-1 PG 17 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Medicine, General & Internal; Physiology; Sport Sciences SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; General & Internal Medicine; Physiology; Sport Sciences GA BJS87 UT WOS:000267119300006 ER PT B AU Botein, SH Veves, A Horton, E AF Botein, Susan Herzlinger Veves, Aristidis Horton, Edward BE Regensteiner, JG Reusch, JEB Stewart, KJ Veves, A TI Conditions That May Interfere with Exercise SO DIABETES AND EXERCISE SE Contemporary Diabetes LA English DT Article; Book Chapter DE Retinopathy; Neuropathy; Cardiovascular disease; Exercise ID DIABETIC AUTONOMIC NEUROPATHY; MYOCARDIAL-INFARCTION; GRADED-EXERCISE; POSTEXERCISE ALBUMINURIA; BLOOD-PRESSURE; NIDDM PATIENTS; IDDM PATIENTS; MICROALBUMINURIA; RESPONSES; CAPACITY AB Exercise often has many positive effects on diabetes management, including improved glycemic control, assistance with weight maintenance, increases cardiorespiratory fitness, and general sense of well-being. However, as diabetic patients can also have other conditions that can be negatively affected by exercise, such as cardiovascular disease and neuropathy that makes them vulnerable to foot problems and retinopathy, exercise should be carefully monitored by the health provider, especially during the initiation period. Therefore, careful evaluation of patients for complications that may present incremental risks or interfere with the capacity for exercise is an important first step in planning an appropriate exercise program. This chapter will review the currently available guidelines and will provide practical information regarding the implementation of exercise programs in diabetic patients with conditions that may interfere with exercise and will need additional attention. C1 [Botein, Susan Herzlinger] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab,Clin Res Ctr, Boston, MA 02115 USA. [Horton, Edward] Harvard Univ, Sch Med, Joslin Diabet Ctr, Clin Res Ctr, Boston, MA 02115 USA. [Veves, Aristidis] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Microcirculat Lab, Joslin Beth Israel Deaconess Foot Ctr,Dept Surg, Boston, MA 02115 USA. RP Botein, SH (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab,Clin Res Ctr, Boston, MA 02115 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-926-0 J9 CONTEMP DIABETES PY 2009 BP 281 EP 290 DI 10.1007/978-1-59745-260-1_13 D2 10.1007/978-1-59745-260-1 PG 10 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Medicine, General & Internal; Physiology; Sport Sciences SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; General & Internal Medicine; Physiology; Sport Sciences GA BJS87 UT WOS:000267119300013 ER PT B AU Watson, GS Craft, S AF Watson, G. Stennis Craft, Suzanne BE Biessels, GJ Luchsinger, JA TI The Role of Insulin Resistance in Age-Related Cognitive Decline and Dementia SO DIABETES AND THE BRAIN SE Contemporary Diabetes LA English DT Article; Book Chapter DE Alzheimer's disease; Apolipoprotein E; Beta amyloid; Diabetes; Diet and exercise; Glucose; Inflammation; Insulin; Insulin resistance; IGF-1; Intranasal; Memory; PPAR-gamma ID CENTRAL-NERVOUS-SYSTEM; IMPAIRED GLUCOSE-TOLERANCE; APOLIPOPROTEIN-E GENOTYPE; GROWTH-FACTOR EXPRESSION; SPORADIC ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; OXIDE SYNTHASE EXPRESSION; NECROSIS-FACTOR-ALPHA; FREE FATTY-ACIDS; PEROXISOME PROLIFERATOR AB The role of insulin in peripheral energy metabolism has been well described, and converging evidence has identified a role for insulin in central nervous system functions. Epidemiological studies support an important relationship between diabetes and other insulin-resistant conditions, and cognitive functioning. For example, diabetes increases the risk for memory loss, and treating diabetes can reverse memory loss. These studies have also identified a reciprocal relationship between insulin resistance and dementia, such that one condition increases the risk for the other. A substantial body of work has explored the role of insulin in regulating brain glucose metabolism, memory function, inflammatory responses, and amyloid concentrations. Knowledge of these relationships has suggested that increasing brain insulin activity may have a beneficial impact on memory and may serve as the basis for novel therapeutic strategies for Alzheimer's disease. Three such strategies include intranasal administration of insulin, drugs that improve insulin sensitivity, and diet and exercise C1 [Watson, G. Stennis; Craft, Suzanne] Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound, Seattle, WA 98108 USA. RP Watson, GS (reprint author), Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound, Seattle, WA 98108 USA. EM gswatson@u.washington.edu; scraft@u.washington.edu NR 107 TC 0 Z9 0 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-850-8 J9 CONTEMP DIABETES PY 2009 BP 433 EP 457 DI 10.1007/978-1-60327-850-8_18 D2 10.1007/978-1-60327-850-8 PG 25 WC Endocrinology & Metabolism; Medicine, General & Internal; Neurosciences SC Endocrinology & Metabolism; General & Internal Medicine; Neurosciences & Neurology GA BLZ66 UT WOS:000271604300018 ER PT J AU Maciejewski, ML Liu, CF Fihn, SD AF Maciejewski, Matthew L. Liu, Chuan-Fen Fihn, Stephan D. TI Performance of Comorbidity, Risk Adjustment, and Functional Status Measures in Expenditure Prediction for Patients With Diabetes SO DIABETES CARE LA English DT Article ID REPORTED HEALTH-STATUS; CASE-MIX; SEVERITY INDEX; CARE; VALIDATION; QUALITY; MODEL; POPULATION; MORTALITY; SELECTION AB OBJECTIVE - To compare the ability of generic comorbidity and risk adjustment measures, a diabetes-specific measure, and a self-reported functional status measure to explain variation in health care expenditures for individuals with diabetes. RESEARCH DESIGN AND METHODS - This study included a retrospective cohort of 3,092 diabetic veterans participating in a multisite trial. Two comorbidity measures, four risk adjusters, a functional Status measure, a diabetes complication count, and baseline expenditures were constructed from administrative and survey data. Outpatient, inpatient, and total expenditure models were estimated using ordinary least squares regression. Adjusted R(2) statistics and predictive ratios were compared across measures to assess overall explanatory power and explanatory power of low- and high-cost subgroups. RESULTS - Administrative data-based risk adjusters performed better than the comorbidity, functional status, and diabetes-specific measures in all expenditure models. The diagnostic cost groups (DCGs) measure had the greatest predictive power overall and for the low- and high-cost subgroups, while the diabetes-specific measure had the lowest predictive power. A model with DCGs and the diabetes-specific measure modestly improved predictive power. CONCLUSIONS - Existing generic measures can be useful for diabetes-specific research and policy applications, but more predictive diabetes-specific measures are needed. C1 [Maciejewski, Matthew L.] Durham VA Med Ctr, Hlth Serv Res & Dev, Dept Vet Affairs, Durham, NC USA. [Maciejewski, Matthew L.] Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. [Liu, Chuan-Fen; Fihn, Stephan D.] Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Washington, DC USA. [Liu, Chuan-Fen; Fihn, Stephan D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Hlth Serv Res & Dev, Dept Vet Affairs, Durham, NC USA. EM matthew.maciejewski@va.gov FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Health Services Research and Development Service (HSRD) [LIP 61-105, SDR 96-002, IIR 99-376] FX No potential conflicts of interest relevant to this article were reported. Comments from Sarah Krein, the manuscript editor, two anonymous reviewers, and Outstanding research assistance from Mark Perkins are appreciated. NR 25 TC 25 Z9 25 U1 1 U2 8 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 JAN PY 2009 VL 32 IS 1 BP 75 EP 80 DI 10.2337/dc08-1099 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390UA UT WOS:000262188000016 PM 18945927 ER PT J AU Nathan, DM Buse, JB Davidson, MB Ferrannini, E Holman, RR Sherwin, R Zinman, B AF Nathan, David M. Buse, John B. Davidson, Mayer B. Ferrannini, Ele Holman, Rury R. Sherwin, Robert Zinman, Bernard TI Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes SO DIABETES CARE LA English DT Article ID BLOOD-GLUCOSE CONTROL; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE INSULIN THERAPY; IMPROVED GLYCEMIC CONTROL; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; MICROVASCULAR COMPLICATIONS; EXENATIDE EXENDIN-4; LIFE-STYLE AB The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues Surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience. C1 [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Zinman, Bernard] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Sherwin, Robert] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Sherwin, Robert] Yale Univ, Sch Med, Yale Ctr Clin Invest, New Haven, CT 06510 USA. [Holman, Rury R.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England. [Ferrannini, Ele] Univ Pisa, Dept Internal Med, Pisa, Italy. [Davidson, Mayer B.] Charles R Drew Univ Med & Sci, Clin Ctr Res Excellence, Los Angeles, CA 90059 USA. [Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013 NR 92 TC 1586 Z9 1686 U1 6 U2 104 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2009 VL 32 IS 1 BP 193 EP 203 DI 10.2337/dc08-9025 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390UA UT WOS:000262188000042 PM 18945920 ER PT J AU Funnel, MM Brown, TL Childs, BP Haas, LB Hosey, GM Jensen, B Maryniuk, M Peyrot, M Piette, JD Reader, D Diminerio, LM Weinger, K Weiss, MA AF Funnel, Martha M. Brown, Tammy L. Childs, Belinda P. Haas, Linda B. Hosey, Gwen M. Jensen, Brain Maryniuk, Melinda Peyrot, Mark Piette, John D. Reader, Diane Diminerio, Linda M. Weinger, Katie Weiss, Michael A. TI National Standards for Diabetes Self-Management Education SO DIABETES CARE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC DISEASE MANAGEMENT; IMPROVE GLYCEMIC CONTROL; PRIMARY-CARE PATIENTS; HEALTH-CARE; COMPLICATIONS TRIAL; PATIENT EDUCATION; AFRICAN-AMERICAN; COMMUNITY-HEALTH; CHRONIC ILLNESS C1 [Funnel, Martha M.] Univ Michigan, Dept Med Educ, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. [Brown, Tammy L.] Indiana Hlth Serv, Albuquerque, NM USA. [Childs, Belinda P.] MidAmer Diabet Diabet Translat, Wichita, KS USA. [Haas, Linda B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Hosey, Gwen M.] Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Jensen, Brain] Lakeshore Apothacare, Two Rivers, WI USA. [Maryniuk, Melinda; Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Peyrot, Mark] Loyola Coll, Baltimore, MD 21210 USA. [Piette, John D.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan, Dept Internal Med, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. [Reader, Diane] Int Diabet Ctr, Minneapolis, MN USA. [Diminerio, Linda M.] Univ Pittsburgh, Med Ctr, Inst Diabet, Pittsburgh, PA USA. [Weiss, Michael A.] Patient Centered Solut, Pittsburgh, PA USA. RP Funnel, MM (reprint author), Univ Michigan, Dept Med Educ, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. EM mfunnell@umich.edu RI McDowell, Joan/H-3159-2014 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [NIH5P60, DK20572, 1 R18 0K062323] FX Work on this article was supported in part by grant nos, NIH5P60 DK20572 and 1 R18 0K062323 from the National Institute of Diabetes and Digestive and Kidney Diseases Of the National Institutes of Health.; The Task Force gratefully acknowledges the assistance and Support of Pauhna MD, CDE, of the American Diabetes Association; Lon Porter, MBA, RD, CAE, Of the American Association of Diabetes Educators; and Karmeen Kutkarni, MS, RD, BC-ADM, Past President, Health Care and Education of the Arrierican Diabetes Association; Malinda Peeples, MS, PN, CDE, Past President of the American Association of Diabetes Educators; and Carole' Mensing, RN, MA, CDE, for their insights and helpful suggestions.; We also gratefully acknowledge the work of the previous Task Force for the National Standards for DSME: Carole' Mensing, RN, MA, CDE; Jackie Boucher, MS, RD, LD, CDE; Marj. orie Cypress, MS, C-ANP, CDE; Katie Weinger, EdD, RN; Kathryn Mulcahy, MSN, RN, CDE; Patricia BarLa, RN, MPH, CDE; Gwen Hosey, MS, ARNP, CDE; Wendy Kopher, RN, C, CDE, HTP; Andrea Lasichak, MS, RD, CDE Betty Lamb, RN, MSN; MaVOUrneen Mangan, RN, MS, ANP, C, CDE; Jan Norman, RD, CDE; Jon Tanja, BS, MS, RPH; Linda Yauk, MS, RD, LD, CDE; Kimberlyclawn NR 164 TC 85 Z9 89 U1 2 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2009 VL 32 SU 1 BP S87 EP S94 DI 10.2337/dc09-S087 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390UD UT WOS:000262188300010 PM 19118294 ER PT B AU Rizzotto, JAM Giusti, J Higgins, L AF Rizzotto, Jo-Anne M. Giusti, Judy Higgins, Laurie BE Tsatsoulis, A Wyckoff, J Brown, FM TI Nutrition and Pregnancy SO DIABETES IN WOMEN SE Contemporary Diabetes LA English DT Article; Book Chapter DE preconception counseling; diabetes and pregnancy; meal planning; weight gain; breast-feeding; celiac diaease ID AMERICAN-DIETETIC-ASSOCIATION; CELIAC-DISEASE; FATTY-ACIDS; DIABETES-MELLITUS; UNITED-STATES; LIFE-STYLE; POSITION; RISK; MULTICENTER; DIETITIANS AB Pregnancy complicated by diabetes presents unique challenges for women with preexisting diabetes and those with gestational diabetes. All women with preexisting diabetes, who are of childbearing years, should receive preconception counseling to prepare for pregnancy. Prenatal counseling and care should include a team consisting of healthcare providers who are well versed in the care of diabetes and pregnancy. Women with diabetes should receive Medical Nutrition Therapy (MNT) counseling prior to and throughout pregnancy. The goals of MNT and meal planning are (1) to provide adequate calories and nutrients to achieve target pregnancy weight gain and glycemic control and (2) to promote lifelong healthy lifestyle behaviors. These goals will optimize maternal, fetal, and perinatal outcomes and minimize pregnancy complications. They require balancing food and activity with insulin to meet glucose goals. C1 [Rizzotto, Jo-Anne M.] Joslin Diabet Ctr, Joslin Clin, Boston, MA 02215 USA. RP Rizzotto, JAM (reprint author), Joslin Diabet Ctr, Joslin Clin, Boston, MA 02215 USA. NR 40 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-249-0 J9 CONTEMP DIABETES PY 2009 BP 255 EP 272 DI 10.1007/978-1-60327-250-6_14 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BMR52 UT WOS:000273398100014 ER PT B AU Takoudes, TC AF Takoudes, Tamara C. BE Tsatsoulis, A Wyckoff, J Brown, FM TI Obstetric Care of the Woman with Diabetes SO DIABETES IN WOMEN SE Contemporary Diabetes LA English DT Article; Book Chapter DE Hemoglobin A1c; Congenital anomalies; Miscarriage; Preeclampsia; Stillbirth; Insulin; Macrosomia ID NEURAL-TUBE DEFECTS; CONGENITAL HEART-DISEASE; FETAL LUNG MATURITY; BIOPHYSICAL PROFILE; SHOULDER DYSTOCIA; DEVELOPMENTAL DAMAGE; EXPECTANT MANAGEMENT; THYROID-DYSFUNCTION; PRENATAL-DIAGNOSIS; CESAREAN-SECTION AB Diabetes increases the risk of complications during pregnancy. Starting in the preconception period and continuing throughout pregnancy and postpartum, heightened surveillance is necessary in order to achieve a healthy outcome for both mother and neonate. This chapter will outline the complications that may arise during pregnancies complicated by diabetes and suggest a management scheme for the gravid woman with diabetes. Specific concerns in the first trimester include an increased risk of miscarriage and careful evaluation of the maternal risks specific to the patient's cardiovascular, renal, thyroid, and ophthalmologic status. In the early second trimester, fetal testing for congenital birth defects and other diagnostic procedures are recommended. This trimester is complicated by increasing insulin requirements that usually continue into the third trimester. In late pregnancy, concern shifts to fetal size, preeclampsia, stillbirth, and deciding delivery timing and route. Labor and delivery is a unique time for the gravid woman with diabetes, as there are specific challenges with changing insulin requirements related to labor, mode of delivery, and type of diabetes. This chapter will give a brief overview of the use of insulin during pregnancy, intrapartum as well as postpartum, but please refer to Chap. 17 for a more complete discussion. Postpartum concerns in women with diabetes include an increased risk of endometritis and wound infection, postpartum thyroiditis, decreased insulin requirements, and contraception challenges. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Pregnancy Program,Dept Obstet & Gyn, Boston, MA 02215 USA. RP Takoudes, TC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Pregnancy Program,Dept Obstet & Gyn, Boston, MA 02215 USA. NR 92 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-249-0 J9 CONTEMP DIABETES PY 2009 BP 291 EP 305 DI 10.1007/978-1-60327-250-6_16 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BMR52 UT WOS:000273398100016 ER PT B AU Cohen, AL Karumanchi, SA AF Cohen, Allison L. Karumanchi, S. Ananth BE Tsatsoulis, A Wyckoff, J Brown, FM TI Preeclampsia SO DIABETES IN WOMEN SE Contemporary Diabetes LA English DT Article; Book Chapter DE Preeclampsia; Vascular endothelial growth factor; Soluble fms-like tyrosine kinase 1 receptor; Placental like growth factor; Endoglin; Diabetes; Proteinuria; Angiogenesis; Gestational hypertension ID PREGNANCY-INDUCED HYPERTENSION; PLACENTAL GROWTH-FACTOR; CIRCULATING ANGIOGENIC FACTORS; HEALTHY NULLIPAROUS WOMEN; ENDOTHELIAL-CELL FUNCTION; RENIN-ANGIOTENSIN SYSTEM; POPULATION-BASED COHORT; TYPE-1 DIABETIC WOMEN; TUMOR-NECROSIS-FACTOR; GESTATIONAL HYPERTENSION AB Preeclampsia is a syndrome of new-onset hypertension and proteinuria after 20-weeks gestation in a previously normotensive woman. Preeclampsia is a leading cause of maternal, fetal, and neonatal morbidity and mortality throughout the world. There are multiple risk factors for preeclampsia, including pregestational diabetes and obesity. Women with preeclampsia have an increased risk of recurrence in subsequent pregnancies and have an increased long-term risk of cardiovascular disease. Although the etiology of preeclampsia is still unclear, recent studies have elucidated the pathophysiology underlying, the disease. All of the clinical features of preeclampsia can be explained as a maternal response to placental-derived toxic factors that lead to generalized endothelial dysfunction. Recent evidence has shown alterations in angiogenic factors, including an increase in soluble fms-like tyrosine kinase 1 (sFlt-1), a naturally occurring circulating vascular endothelial growth factor (VEGF) antagonist, in women with preeclampsia. Soluble endoglin (sEng), a novel placenta-derived soluble anti-angiogenic protein appears to be another mediator of preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia, but also antedate clinical symptoms by several weeks. There are also immunologic changes and changes in the renin-angiotensin system that may lead to the development of preeclampsia. Women with pregestational diabetes have an increased risk of preeclampsia, especially those with underlying renal disease. It is especially difficult to diagnose preeclampsia in these women with underlying hypertension and proteinuria. In this chapter, we will discuss the epidemiology and the recent developments in the pathogenesis of preeclampsia. We will also highlight the contribution of pregestational diabetes in preeclampsia and discuss the long term of implications for maternal health in women with a history of preeclampsia. C1 [Cohen, Allison L.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Cohen, AL (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 123 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-249-0 J9 CONTEMP DIABETES PY 2009 BP 341 EP 357 DI 10.1007/978-1-60327-250-6_19 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BMR52 UT WOS:000273398100019 ER PT J AU Rizzotto, JAM Giusti, J Higgins, L AF Rizzotto, Jo-Anne M. Giusti, Judy Higgins, Laurie BE Tsatsoulis, A Wyckoff, J Brown, FM TI Nutrition and Pregnancy SO DIABETES IN WOMEN: PATHOPHYSIOLOGY AND THERAPY SE Contemporary Diabetes LA English DT Article; Book Chapter DE preconception counseling; diabetes and pregnancy; meal planning; weight gain; breast-feeding; celiac diaease ID AMERICAN-DIETETIC-ASSOCIATION; CELIAC-DISEASE; FATTY-ACIDS; DIABETES-MELLITUS; UNITED-STATES; LIFE-STYLE; POSITION; RISK; MULTICENTER; DIETITIANS AB Pregnancy complicated by diabetes presents unique challenges for women with preexisting diabetes and those with gestational diabetes. All women with preexisting diabetes, who are of childbearing years, should receive preconception counseling to prepare for pregnancy. Prenatal counseling and care should include a team consisting of healthcare providers who are well versed in the care of diabetes and pregnancy. Women with diabetes should receive Medical Nutrition Therapy (MNT) counseling prior to and throughout pregnancy. The goals of MNT and meal planning are (1) to provide adequate calories and nutrients to achieve target pregnancy weight gain and glycemic control and (2) to promote lifelong healthy lifestyle behaviors. These goals will optimize maternal, fetal, and perinatal outcomes and minimize pregnancy complications. They require balancing food and activity with insulin to meet glucose goals. C1 [Rizzotto, Jo-Anne M.] Joslin Diabet Ctr, Joslin Clin, Boston, MA 02215 USA. RP Rizzotto, JAM (reprint author), Joslin Diabet Ctr, Joslin Clin, Boston, MA 02215 USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-250-6 J9 CONTEMP DIABETES PY 2009 BP 255 EP 272 DI 10.1007/978-1-60327-250-6_14 D2 10.1007/978-1-60327-250-6 PG 18 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BLZ65 UT WOS:000271599700014 ER PT J AU Takoudes, TC AF Takoudes, Tamara C. BE Tsatsoulis, A Wyckoff, J Brown, FM TI Obstetric Care of the Woman with Diabetes SO DIABETES IN WOMEN: PATHOPHYSIOLOGY AND THERAPY SE Contemporary Diabetes LA English DT Article; Book Chapter DE Hemoglobin A1c; Congenital anomalies; Miscarriage; Preeclampsia; Stillbirth; Insulin; Macrosomia ID NEURAL-TUBE DEFECTS; CONGENITAL HEART-DISEASE; FETAL LUNG MATURITY; BIOPHYSICAL PROFILE; SHOULDER DYSTOCIA; DEVELOPMENTAL DAMAGE; EXPECTANT MANAGEMENT; THYROID-DYSFUNCTION; PRENATAL-DIAGNOSIS; CESAREAN-SECTION AB Diabetes increases the risk of complications during pregnancy. Starting in the preconception period and continuing throughout pregnancy and postpartum, heightened surveillance is necessary in order to achieve a healthy outcome for both mother and neonate. This chapter will outline the complications that may arise during pregnancies complicated by diabetes and suggest a management scheme for the gravid woman with diabetes. Specific concerns in the first trimester include an increased risk of miscarriage and careful evaluation of the maternal risks specific to the patient's cardiovascular, renal, thyroid, and ophthalmologic status. In the early second trimester, fetal testing for congenital birth defects and other diagnostic procedures are recommended. This trimester is complicated by increasing insulin requirements that usually continue into the third trimester. In late pregnancy, concern shifts to fetal size, preeclampsia, stillbirth, and deciding delivery timing and route. Labor and delivery is a unique time for the gravid woman with diabetes, as there are specific challenges with changing insulin requirements related to labor, mode of delivery, and type of diabetes. This chapter will give a brief overview of the use of insulin during pregnancy, intrapartum as well as postpartum, but please refer to Chap. 17 for a more complete discussion. Postpartum concerns in women with diabetes include an increased risk of endometritis and wound infection, postpartum thyroiditis, decreased insulin requirements, and contraception challenges. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Sch Med,Joslin Diabet Pregnancy Program, Boston, MA 02215 USA. RP Takoudes, TC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Sch Med,Joslin Diabet Pregnancy Program, Boston, MA 02215 USA. NR 92 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-250-6 J9 CONTEMP DIABETES PY 2009 BP 291 EP 305 DI 10.1007/978-1-60327-250-6_16 D2 10.1007/978-1-60327-250-6 PG 15 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BLZ65 UT WOS:000271599700016 ER PT J AU Cohen, AL Karumanchi, SA AF Cohen, Allison L. Karumanchi, S. Ananth BE Tsatsoulis, A Wyckoff, J Brown, FM TI Preeclampsia SO DIABETES IN WOMEN: PATHOPHYSIOLOGY AND THERAPY SE Contemporary Diabetes LA English DT Article; Book Chapter DE Preeclampsia; Vascular endothelial growth factor; Soluble fms-like tyrosine kinase 1 receptor; Placental like growth factor; Endoglin; Diabetes; Proteinuria; Angiogenesis; Gestational hypertension ID PREGNANCY-INDUCED HYPERTENSION; PLACENTAL GROWTH-FACTOR; CIRCULATING ANGIOGENIC FACTORS; HEALTHY NULLIPAROUS WOMEN; ENDOTHELIAL-CELL FUNCTION; RENIN-ANGIOTENSIN SYSTEM; POPULATION-BASED COHORT; TYPE-1 DIABETIC WOMEN; TUMOR-NECROSIS-FACTOR; GESTATIONAL HYPERTENSION AB Preeclampsia is a syndrome of new-onset hypertension and proteinuria after 20-weeks gestation in a previously normotensive woman. Preeclampsia is a leading cause of maternal, fetal, and neonatal morbidity and mortality throughout the world. There are multiple risk factors for preeclampsia, including pregestational diabetes and obesity. Women with preeclampsia have an increased risk of recurrence in subsequent pregnancies and have an increased long-term risk of cardiovascular disease. Although the etiology of preeclampsia is still unclear, recent studies have elucidated the pathophysiology underlying the disease. All of the clinical features of preeclampsia can be explained as a maternal response to placental-derived toxic factors that lead to generalized endothelial dysfunction. Recent evidence has shown alterations in angiogenic factors, including an increase in soluble fms-like tyrosine kinase 1 (sFlt-1), a naturally occurring circulating vascular endothelial growth factor (VEGF) antagonist, in women with preeclampsia. Soluble endoglin (sEng), a novel placenta-derived soluble anti-angiogenic protein appears to be another mediator of preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia, but also antedate clinical symptoms by several weeks. There are also immunologic changes and changes in the renin-angiotensin system that may lead to the development of preeclampsia. Women with pregestational diabetes have an increased risk of preeclampsia, especially those with underlying renal disease. It is especially difficult to diagnose preeclampsia in these women with underlying hypertension and proteinuria. In this chapter, we will discuss the epidemiology and the recent developments in the pathogenesis of preeclampsia. We will also highlight the contribution of pregestational diabetes in preeclampsia and discuss the long term of implications for maternal health in women with a history of preeclampsia. C1 [Cohen, Allison L.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Cohen, AL (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 123 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-250-6 J9 CONTEMP DIABETES PY 2009 BP 341 EP 357 DI 10.1007/978-1-60327-250-6_19 D2 10.1007/978-1-60327-250-6 PG 17 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BLZ65 UT WOS:000271599700019 ER PT J AU Izumi, Y Satterfield, K Lee, S Harkless, LB Lavery, LA AF Izumi, Yuki Satterfield, Kathleen Lee, Shuko Harkless, Lawrence B. Lavery, Lawrence A. TI Mortality of first-time amputees in diabetics: A 10-year observation SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetic foot; Mortality; Amputation ID LOWER-EXTREMITY AMPUTATION; 6.5-YEAR FOLLOW-UP; MAJOR AMPUTATION; LOWER-LIMB; FOOT PROBLEMS; SURVIVAL; POPULATION; DISEASE; REAMPUTATION; PROGNOSIS AB Aims: We analyze mortality of first-time diabetic amputees by stratifying by level of amputation, differentiating short-term and long-term mortality. Methods: We evaluated 277 diabetic patients who received their first lower extremity amputation (LEA) during 1993-97. Subjects were followed until December 2003, and categorized by level of amputation. We compared the mortality difference by level for 0-10 years, 0-10 months, and 10 months-10 years, and examined the association of comorbid conditions and death for each level. Results: We found a significant difference in mortality by amputation level for 0-10 years (p < 0.05) and < 10 months (p < 0.01) survival, but not for the one of 10 months-10 years. For major amputees deceased within 10 months, sepsis was as frequent a cause of death as cardiovascular disease. in distal. amputees, CVD, CAD and ESRD were strongly associated with death, but only CAD was associated death among major amputees. Conclusion: For diabetic patients undergoing first LEAS, the mortality of major amputees was worse than that of minor amputees due to the difference in first 10-month mortality. The history of comorbid conditions in first-time major amputees was less important than in minor amputees since sepsis was the frequent cause of death in major amputees in this early period. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Izumi, Yuki] Natl Hosp Org, Kyoto Med Ctr, WHO, Collaborating Ctr Diabet, Kyoto 6128555, Japan. [Satterfield, Kathleen] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthopaed, San Antonio, TX 78229 USA. [Lee, Shuko] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res & Dev Serv, San Antonio, TX USA. [Harkless, Lawrence B.] Western Univ Hlth Sci, Coll Podiatr Med, Pomona, CA 91766 USA. [Lavery, Lawrence A.] Texas A&M Univ, Coll Med, Hlth Sci Ctr, Temple, TX 76508 USA. [Lavery, Lawrence A.] Scott & White Hosp, Temple, TX USA. RP Izumi, Y (reprint author), Natl Hosp Org, Kyoto Med Ctr, WHO, Collaborating Ctr Diabet, 1-1 Mukaihata Cho Fukakusa, Kyoto 6128555, Japan. EM dfootjapan@hotmail.co.jp OI Lavery, Lawrence/0000-0002-7920-9952 NR 22 TC 26 Z9 27 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD JAN PY 2009 VL 83 IS 1 BP 126 EP 131 DI 10.1016/j.diabres.2008.09.005 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 398VC UT WOS:000262758600019 PM 19097667 ER PT J AU Nathan, D Buse, JB Davidson, MB Ferrannini, E Holman, RR Sherwin, R Zinman, B AF Nathan, D. M. Buse, J. B. Davidson, M. B. Ferrannini, E. Holman, R. R. Sherwin, R. Zinman, B. TI Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes SO DIABETOLOGIA LA English DT Article ID BLOOD-GLUCOSE CONTROL; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE INSULIN THERAPY; IMPROVED GLYCEMIC CONTROL; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; MICROVASCULAR COMPLICATIONS; EXENATIDE EXENDIN-4; LIFE-STYLE AB The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience. C1 [Nathan, D. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Buse, J. B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Davidson, M. B.] Charles R Drew Univ Med & Sci, Clin Ctr Res Excellence, Los Angeles, CA 90059 USA. [Ferrannini, E.] Univ Pisa, Dept Internal Med, Pisa, Italy. [Holman, R. R.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England. [Sherwin, R.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Sherwin, R.] Yale Univ, Sch Med, Yale Ctr Clin Invest, New Haven, CT USA. [Zinman, B.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Nathan, D (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013 FU Sanofi Aventis; GlaxoSmithKline FX D. M. Nathan has received a research grant for investigator-initiated research from Sanofi Aventis and support for educational programs from GlaxoSmithKline. J.B. Buse has conducted research and/or served on advisory boards under contract between the University of North Carolina and Amylin, Becton-Dickinson, Bristol-Myers Squibb, Hoffman-LaRoche, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Merck, Novartis, Pfizer and Sanofi Aventis. M. B. Davidson has received research support from Eli Lilly, Merck and Pfizer; has served on advisory boards for Amylin, GlaxoSmithKline, Merck and Sanofi Aventis; and has been on speakers bureaus for Amylin, Eli Lilly, GlaxoSmithKline and Pfizer. E. Ferrannini has received research support from AstraZeneca, Merck Sharpe & Dohme and Novartis and serves on scientific advisory boards for Amylin, AstraZeneca, GlaxoSmithKline, Roche, Merck Sharpe & Dohme, Novartis, Sanofi Aventis, Boehringer Ingelheim and Takeda. R. R. Holman has received research support from Bristol-Myers Squibb, GlaxoSmithKline, Merck Sante, Novo Nordisk, Pfizer and Pronova and has served on advisory boards and/or received honoraria for speaking engagements from Amylin, GlaxoSmithKline, Lilly, Merck Sharp & Dohme, Novartis and Sanofi Aventis. R. Sherwin has served on advisory boards for Amylin, AstraZeneca, Boehringer Ingelheim, DiObex, Eli Lilly, Insulet, Merck, MannKind and Novartis. B. Zinman has received research support from GlaxoSmithKline, Merck, Novartis and Novo Nordisk and has been a member of scientific advisory boards and/or received honoraria for speaking engagements from Amylin, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, Sanofi Aventis and Servier. NR 92 TC 374 Z9 391 U1 2 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2009 VL 52 IS 1 BP 17 EP 30 DI 10.1007/s00125-008-1157-y PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 379DC UT WOS:000261375400003 PM 18941734 ER PT J AU Ison, MG Rosenberg, ES AF Ison, Michael G. Rosenberg, Eric S. BE Hayden, RT Carroll, KC Tang, YW Wolk, DM TI RNA Respiratory Viruses SO DIAGNOSTIC MICROBIOLOGY OF THE IMMUNOCOMPROMISED HOST LA English DT Article; Book Chapter ID LUNG-TRANSPLANT RECIPIENTS; REVERSE TRANSCRIPTION-PCR; POLYMERASE-CHAIN-REACTION; HUMAN METAPNEUMOVIRUS INFECTION; STEM-CELL TRANSPLANT; INFLUENZA-A VIRUSES; BONE-MARROW-TRANSPLANTATION; LINKED-IMMUNOSORBENT-ASSAY; HUMAN CORONAVIRUSES 229E; REAL-TIME PCR C1 [Ison, Michael G.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Ison, Michael G.] Northwestern Univ, Feinberg Sch Med, Organ Transplantat Transplant & Immunocompromised, Chicago, IL 60611 USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Dept Med, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Dept Pathol, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. RP Ison, MG (reprint author), Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. NR 219 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-545-5 PY 2009 BP 141 EP 160 PG 20 WC Infectious Diseases; Medical Laboratory Technology; Microbiology SC Infectious Diseases; Medical Laboratory Technology; Microbiology GA BOY49 UT WOS:000278062500009 ER PT J AU Salat, DH Lee, SY Yu, P Setty, B Rosas, HD Grant, PE AF Salat, David H. Lee, Stephanie Y. Yu, Peng Setty, Bindu Rosas, H. Diana Grant, P. Ellen BE JohansenBerg, H Behrens, TEJ TI DTI in Development and Aging SO DIFFUSION MRI: FROM QUANTITATIVE MEASUREMENT TO IN VIVO NEUROANATOMY LA English DT Article; Book Chapter DE Aging; development; diffusion tensor imaging; white matter; prefrontal; cognition; Alzheimer's disease; myelin; hyperintensities; leukoaraiosis; tractography ID DIFFUSION-TENSOR MRI; MILD COGNITIVE IMPAIRMENT; CEREBRAL WHITE-MATTER; AGE-RELATED-CHANGES; EARLY ALZHEIMERS-DISEASE; NORMAL BRAIN MATURATION; VOXEL-BASED MORPHOMETRY; MAGNETIC-RESONANCE; IN-VIVO; CORPUS-CALLOSUM AB Development and senescence of neural systems is associated with profound alterations in connective anatomy and tissue architecture. Classical neuroimaging has allowed the in vivo examination of these dynamic changes, and prior studies utilizing quantitative methods have revealed many basic principles of cerebral organization across the lifespan. Recent developments in diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) have provided a significant advance in the parameters available for the in vivo examination of tissue changes across the lifespan. The microstructural measurements provided by diffusion imaging are particularly helpful in charting the change in myeloarchitecture and connectivity that occurs during brain development, as well as mapping the decline or alterations in brain networks that result from aging and disease. Diffusion methods may allow the measurement of tissue parameters that precede functional or macroscopic structural alterations, or even differentiate among the various histological processes that have been documented to occur across the lifespan. Knowledge of normal variations in diffusion parameters across the lifespan is necessary to develop the sensitivity to detect early changes in tissue architecture which result from disease. Here we review the current literature examining the use of diffusion metrics to gain neurobiological insight into the developing and aging brain, as well as work exploring the clinical utility of diffusion imaging towards understanding patterns of abnormal development and age-associated neurodegenerative disease. We additionally review related concepts, including discussion of the common metrics obtained from diffusion imaging and how lifespan changes in diffusion metrics relate to classically utilized macrostructural volumetric measures. With the great promise of diffusion imaging, it will be critical to advance procedures for data acquisition and analysis that provide the most accurate and sensitive measures of anatomy and microstructure possible. In this regard, we review some of the current limitations and challenges in the application of diffusion imaging to address clinical questions, and discuss the great potential for future applications once these challenges are addressed. C1 [Salat, David H.; Yu, Peng; Grant, P. Ellen] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lee, Stephanie Y.; Rosas, H. Diana] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Setty, Bindu] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Salat, DH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Bldg 149,Rm 2301,13th St, Charlestown, MA 02129 USA. NR 230 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-087851-5 PY 2009 BP 205 EP 236 DI 10.1016/B978-0-12-374709-9.00010-9 PG 32 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BCP49 UT WOS:000310964900012 ER PT J AU Kubicki, M Shenton, M AF Kubicki, Marek Shenton, Martha BE JohansenBerg, H Behrens, TEJ TI Diffusion Tensor Imaging and Its Application to Schizophrenia and Related Disorders SO DIFFUSION MRI: FROM QUANTITATIVE MEASUREMENT TO IN VIVO NEUROANATOMY LA English DT Article; Book Chapter DE Schizophrenia; white matter; first episode; chronic; progression; anatomical connectivity; DTI ID WHITE-MATTER INTEGRITY; EARLY-ONSET SCHIZOPHRENIA; SUPERIOR CEREBELLAR PEDUNCLE; FRONTAL-CORTEX CONNECTIONS; 1ST EPISODE SCHIZOPHRENIA; SPECTROSCOPY H-1 MRS; MAGNETIC-RESONANCE; CORPUS-CALLOSUM; 1ST-EPISODE SCHIZOPHRENIA; UNCINATE FASCICULUS AB Since its introduction, diffusion tensor imaging (DTI) has become one of the major tools in clinical and experimental neuroscience, and the most important imaging technique to investigate brain white matter in vivo. Schizophrenia, a widely studied but still poorly understood neuropsychiatric disorder, has been characterized as multifocal brain disease, involving abnormal brain connectivity. The idea of quantifying abnormalities within white matter fiber tracts, which subserve anatomical connections between distant as well as proximal brain regions, has thus fueled an interest in DTI studies in schizophrenia, resulting, to date, in more than 70 original peer-reviewed publications. In this chapter, we review DTI studies in schizophrenia, discussing the findings and their relevance in terms of what we know and do not know about white matter dysfunctions in schizophrenia in order to understand better the nature of schizophrenia pathology. C1 [Kubicki, Marek; Shenton, Martha] Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Kubicki, Marek; Shenton, Martha] Harvard Univ, Sch Med, Boston, MA USA. [Kubicki, Marek; Shenton, Martha] VA Boston Hlth Care Syst, Boston, MA USA. RP Kubicki, M (reprint author), Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, 75 Francis St, Boston, MA 02115 USA. NR 100 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-087851-5 PY 2009 BP 251 EP 270 DI 10.1016/B978-0-12-374709-9.00012-2 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BCP49 UT WOS:000310964900014 ER PT J AU Bradesi, S Mayer, EA AF Bradesi, Sylvie Mayer, Emeran A. TI Experimental Models of Stress and Pain: Do They Help to Develop New Therapies? SO DIGESTIVE DISEASES LA English DT Article DE Irritable bowel syndrome; Animal models; Human experimental medicine models; Drug development; Predictive validity; Intermediate phenotypes ID IRRITABLE-BOWEL-SYNDROME; FUNCTIONAL GASTROINTESTINAL DISORDERS; BRAIN-GUT AXIS; NOXIOUS COLORECTAL DISTENSION; PSEUDO-AFFECTIVE RESPONSES; 5-HT3 RECEPTOR ANTAGONIST; KAPPA-AGONIST FEDOTOZINE; FACTOR-I RECEPTORS; COLONIC DISTENSION; ANIMAL-MODELS AB The majority of functional gastrointestinal disorders are characterised by recurrent abdominal pain, with stress playing an important role in first onset and exacerbation of existing symptoms. These disorders are currently defined by symptom criteria, while their pathophysiology remains controversial and incompletely understood. Modeling these disorders in humans and animals has been difficult. While some of the models have adequate face and construct validity, the predictive validity of most of the models has been disappointing, which has put into question the traditional modeling approach. Similar problems have been encountered in drug development for pain and psychiatric disorders. New approaches have been proposed in the form of reverse translation, which include better characterisation of biological intermediate phenotypes in human disease which can be modeled in humans and in animals. Continuation of the current approach focusing on complex clinical phenotypes is likely to be ineffective for the development of novel and effect treatments. Copyright (C) 2010 S. Karger AG, Basel C1 [Bradesi, Sylvie] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Neurobiol Stress,Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Dept Physiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Dept Psychiat, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bradesi, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Neurobiol Stress,Dept Med, Bldg 115 CURE,11303 Wilshire Blvd, Los Angeles, CA 90095 USA. EM sbradesi@ucla.edu FU Boehringer Ingelheim International GmbH; GSK; Novartis; Avera; Danone FX S. Bradesi has received research support from Boehringer Ingelheim International GmbH. E. A. Mayer is a consultant for GSK, Novartis, Lilly, Avery, Forrest, Ironwood and Danone and has received research support from GSK, Novartis, Avera and Danone. NR 92 TC 6 Z9 6 U1 5 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2009 VL 27 SU 1 BP 55 EP 67 DI 10.1159/000268122 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 566FM UT WOS:000275355500009 PM 20203498 ER PT J AU Sands, BE AF Sands, Bruce E. TI The Placebo Response Rate in Irritable Bowel Syndrome and Inflammatory Bowel Disease SO DIGESTIVE DISEASES LA English DT Article DE Irritable bowel syndrome; Inflammatory bowel disease; Crohn's disease; Ulcerative colitis; Placebo response ID ACTIVE ULCERATIVE-COLITIS; CLINICAL-TRIALS; CROHNS-DISEASE; ALTERNATIVE MEDICINE; CERTOLIZUMAB PEGOL; ACTIVITY INDEX; METAANALYSIS; THERAPY; REMISSION AB The placebo response is the efficacy attributable to a treatment that is thought to have no specific pharmacologic effect on the condition being treated. Although potentially helpful in clinical practice, high and unpredictable placebo response rates present a major impediment to the success of clinical trials in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Diverse factors contribute to the placebo response rates observed in clinical trials. These include patient characteristics, physician factors, frequency of study visits, characteristics of the outcome measures, concomitant treatments, regression to the mean, properties of the intervention and treatment setting, timing of the primary endpoint and natural history of the condition. Measures that may minimize the placebo response in IBD clinical trials include early timing of the primary endpoint, minimizing the number of study visits, restricting the patient population to those with documented inflammation (such as elevated biomarkers of inflammation or evidence of mucosal inflammation), including patients with more severe symptoms (i.e. greater disease activity) and enrolling patients with prior failure of immune modulators or biologics. Attempts to limit the placebo response in IBS studies have proven more difficult. Factors associated with higher placebo response rates in IBS studies include longer duration of treatment, greater number of office visits, frequency of administration of study intervention and overall treatment effect of the active agent under study. In the future, improved understanding of the factors that drive the placebo response rate should lead to more efficient study design and drug development. Copyright (C) 2010 S. Karger AG, Basel C1 [Sands, Bruce E.] Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, MGH Crohns & Colitis Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Sands, BE (reprint author), Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GRJ719, Boston, MA 02114 USA. EM bsands@partners.org NR 22 TC 10 Z9 10 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2009 VL 27 SU 1 BP 68 EP 75 DI 10.1159/000268123 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 566FM UT WOS:000275355500010 PM 20203499 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI Gastroenterology Research Group and Digestive Diseases and Sciences SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material C1 Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90095 USA. EM jake@ucla.edu NR 1 TC 0 Z9 0 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 JAN PY 2009 VL 54 IS 1 BP 5 EP 5 DI 10.1007/s10620-008-0625-z PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 383DD UT WOS:000261653400002 ER PT J AU Sporner, ML Fitzgerald, SG Dicianno, BE Collins, D Teodorski, E Pasquina, PF Cooper, RA AF Sporner, Michelle L. Fitzgerald, Shirley G. Dicianno, Brad E. Collins, Diane Teodorski, Emily Pasquina, Paul F. Cooper, Rory A. TI Psychosocial impact of participation in the National Veterans Wheelchair Games and Winter Sports Clinic SO DISABILITY AND REHABILITATION LA English DT Article DE Exercise; sports; wheelchairs; activities of daily living; quality of life ID SPINAL-CORD-INJURY; PHYSICAL-ACTIVITY; MENTAL-HEALTH; CONTROLLED-TRIAL; EXERCISE; PREVENTION; DEPRESSION; DEPLOYMENT; MOOD; IRAQ AB Purpose. The purpose of this study was to determine the characteristics of individuals who participate in the National Veterans Wheelchair Games (NVWG) and the Winter Sports Clinic (WSC) for veterans with disabilities. In addition, it was of interest to determine how these events had impacted their lives. Method. Participants were recruited at the 20th Winter Sports Clinic, held in Snowmass Colorado and the 26th National Veterans Wheelchair Games held in Anchorage, Alaska. Data of interest included demographic, sport participation information, community integration, self-esteem, and quality of life. A secondary data analysis was completed to determine how comparable individuals who attended the NVWG/WSC were to individuals who did not participate in these events. Results. The 132 participants were a mean age of 47.4 + 13.4 and lived with a disability for an average of 13.4 + 12.1. Participants felt that the NVWG/WSC increased their knowledge of sports equipment (92%), learning sports (89%), mobility skills (84%), and acceptance of disability (84%). The majority of participants stated that the NVWG/WSC improved their life. Of those who participated at the NVWG/WSC, they tended to be more mobile, but have increased physical and cognitive limitations as measured by the CHART when compared to the non-attendees. Conclusions. Recommending veterans participate in events such as the NVWG and WSC can provide psychosocial benefits to veterans with disabilities. C1 [Sporner, Michelle L.; Collins, Diane] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Fitzgerald, Shirley G.] James Haley Tampa VA, Patient Safety Ctr, Tampa, FL USA. [Dicianno, Brad E.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Teodorski, Emily] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Pasquina, Paul F.] Dept Orthoped & Rehabil, Walter Reed Army Med Ctr, Washington, DC USA. [Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Sporner, Michelle L.; Dicianno, Brad E.; Collins, Diane; Teodorski, Emily; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Sporner, Michelle L.; Collins, Diane; Cooper, Rory A.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Fitzgerald, Shirley G.] James A Haley Tampa VA, Patient Safety Ctr, Tampa, FL USA. [Dicianno, Brad E.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Pasquina, Paul F.] Walter Reed Army Med Ctr, Dept Orthoped & Rehabil, Washington, DC 20307 USA. RP Fitzgerald, SG (reprint author), Patient Safety Ctr Inquiry, 11605 N Nebraska Ave, Tampa, FL 33612 USA. EM Shirley.Fitzgerald@va.gov OI Dicianno, Brad/0000-0003-0738-0192 FU VA Center of Excellence, VA Pittsburgh Healthcare System; The Telemedicine and Advanced Technology Research Center [06053001]; HSRRB [A-13839]; Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering [VA B3142C] FX This project was completed solely at the VA Center of Excellence, VA Pittsburgh Healthcare System. This study was supported by The Telemedicine and Advanced Technology Research Center under Proposal Number 06053001, HSRRB Log Number A-13839 and Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering (VA B3142C). NR 36 TC 19 Z9 20 U1 6 U2 29 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2009 VL 31 IS 5 BP 410 EP 418 AR PII 792789939 DI 10.1080/09638280802030923 PG 9 WC Rehabilitation SC Rehabilitation GA 417SM UT WOS:000264098200009 PM 18608391 ER PT J AU Bull, LM White, DL Bray, M Nurgalieva, Z El-Serag, HB AF Bull, L. M. White, D. L. Bray, M. Nurgalieva, Z. El-Serag, H. B. TI Phase I and II enzyme polymorphisms as risk factors for Barrett's esophagus and esophageal adenocarcinoma: a systematic review and meta-analysis SO DISEASES OF THE ESOPHAGUS LA English DT Review DE Barrett's esophagus; epidemiology; esophageal adenocarcinoma; genetic association; GST; single-nucleotide polymorphism (SNP) ID GLUTATHIONE-S-TRANSFERASE; MICROSOMAL EPOXIDE HYDROLASE; SQUAMOUS-CELL-CARCINOMA; ARYLAMINE N-ACETYLTRANSFERASE; LUNG-CANCER RISK; GENETIC POLYMORPHISMS; REFLUX ESOPHAGITIS; MOLECULAR-GENETICS; C609T POLYMORPHISM; ALLELIC VARIANTS AB P>Although several studies have examined the association between phase I/II enzyme polymorphisms and esophageal adenocarcinoma (EAC) and/or Barrett's esophagus (BE), their overall findings remain unclear. We performed a systematic review and meta-analysis to determine whether phase I/II polymorphisms are independent risk factors for either BE or EAC. We employed keyword searches in multiple databases to identify studies published before October 1, 2007. Single-nucleotide polymorphisms (SNPs) examined in >= 3 studies were meta-analyzed to obtain a pooled estimate of effect. Meta-analysis suggested the minor allele for GSTP1 Val105 conveys modest excess risk (odds ratio [OR](BE) = 1.50, 95% confidence interval [CI] 1.16-1.95; OR(EAC) = 1.20, 95% CI 0.94-1.54). No excess risk was observed with GSTM1 null (OR(BE) = 0.77, 95% CI: 0.56-1.08; OR(EAC) = 1.08, 95% CI: 0.79-1.48), GSTT1 null (OR(BE) = 1.35, 95% CI: 0.91-2.01; OR(EAC) = 0.84, 95% CI: 0.48-1.49), or CYP1A Val462 (OR(EAC) = 0.89, 95% CI: 0.40-1.97). Insufficient data existed to meta-analyze remaining SNPs. Our review identified GSTP1(Ile105Val) as a possible risk factor for BE and EAC in Caucasian males. No excess risk was observed for other phase I/II polymorphisms with sufficient data to meta-analyze. Additional studies are needed to determine if GSTP1 conveys excess risk in females or non-Caucasians and to evaluate other phase I/II polymorphisms. C1 [Bull, L. M.; White, D. L.; Bray, M.; Nurgalieva, Z.; El-Serag, H. B.] Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd MS 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU Helis Foundation FX The study is supported in part by a grant from the Helis Foundation. NR 92 TC 11 Z9 11 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2009 VL 22 IS 7 BP 571 EP 587 DI 10.1111/j.1442-2050.2009.00947.x PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 497OX UT WOS:000270070500005 PM 19222528 ER PT J AU Montenovo, M Tatum, RP Figueredo, E Martin, AV Vu, H Quiroga, E Pellegrini, CA Oelschlager, BK AF Montenovo, M. Tatum, R. P. Figueredo, E. Martin, A. Valeria Vu, H. Quiroga, E. Pellegrini, C. A. Oelschlager, B. K. TI Does combined multichannel intraluminal esophageal impedance and manometry predict postoperative dysphagia after laparoscopic Nissen fundoplication? SO DISEASES OF THE ESOPHAGUS LA English DT Article DE dysphagia; esophageal motility; fundoplication; impedance ID GASTROESOPHAGEAL-REFLUX DISEASE; RANDOMIZED CLINICAL-TRIAL; ANTIREFLUX SURGERY; MOTILITY; THERAPY; PERISTALSIS; SYMPTOMS AB P>Laparoscopic Nissen fundoplication (LNF) is an effective treatment for gastroesophageal reflux disease; however, some patients develop dysphagia postoperatively. Manometry is used to evaluate disorders of peristalsis, but has not been proven useful to identify which patients may be at risk for postoperative dysphagia. Multichannel intraluminal impedance (MII) evaluates the effective clearance of a swallowed bolus through the esophagus. We hypothesized that MII combined with manometry may detect those patients most at risk of developing dysphagia after LNF. Between March 2003 and January 2007, 74 patients who agreed to participate in this study were prospectively enrolled. All patients completed a preoperative symptom questionnaire, MII/manometry, and 24-h pH monitoring. All patients underwent LNF. Symptom questionnaires were administered postoperatively at a median of 18 months (range: 6-46 months), and we defined dysphagia (both preoperatively and postoperatively) as occurring more than once a month with a severity >= 4 (0-10 Symptom Severity Index). Thirty-two patients (43%) reported preoperative dysphagia, but there was no significant difference in pH monitoring, lower esophageal sphincter pressure/relaxation, peristalsis, liquid or viscous bolus transit (MII), or bolus transit time (MII) between patients with and without preoperative dysphagia. In those patients reporting preoperative dysphagia, the severity of dysphagia improved significantly from 6.8 +/- 2 to 2.6 +/- 3.4 (P < 0.001) after LNF. Thirteen (17%) patients reported dysphagia postoperatively, 10 of whom (75%) reported some degree of preoperative dysphagia. The presence of postoperative dysphagia was significantly more common in patients with preoperative dysphagia (P = 0.01). Patients with postoperative dysphagia had similar lower esophageal sphincter pressure and relaxation, peristalsis, and esophageal clearance to those without dysphagia. Neither MII nor manometry predicts dysphagia in patients with gastroesophageal reflux disease or its occurrence after LNF. The presence of dysphagia preoperatively is the only predictor of dysphagia after LNF. C1 [Tatum, R. P.] Univ Washington, VA Puget Sound HCS, Dept Surg, Swallowing Ctr, Seattle, WA 98108 USA. RP Tatum, RP (reprint author), Univ Washington, VA Puget Sound HCS, Dept Surg, Swallowing Ctr, 1660 S Columbian Way S-112-Gs,Box 358280, Seattle, WA 98108 USA. EM rtatum@u.washington.edu NR 27 TC 18 Z9 21 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2009 VL 22 IS 8 BP 656 EP 663 DI 10.1111/j.1442-2050.2009.00988.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 524FE UT WOS:000272128400005 PM 19515186 ER PT S AU Purdon, PL Pierce, ET Bonmassar, G Walsh, J Harrell, PG Kwo, J Deschler, D Barlow, M Merhar, RC Lamus, C Mullaly, CM Sullivan, M Maginnis, S Skoniecki, D Higgins, HA Brown, EN AF Purdon, Patrick L. Pierce, Eric T. Bonmassar, Giorgio Walsh, John Harrell, P. Grace Kwo, Jean Deschler, Daniel Barlow, Margaret Merhar, Rebecca C. Lamus, Camilo Mullaly, Catherine M. Sullivan, Mary Maginnis, Sharon Skoniecki, Debra Higgins, Helen-Anne Brown, Emery N. BE Schiff, ND Laureys, S TI Simultaneous Electroencephalography and Functional Magnetic Resonance Imaging of General Anesthesia SO DISORDERS OF CONSCIOUSNESS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 87th Annual Conference of the Association-for-Reseach-in-Nervous-and-Mental-Disease CY DEC 07-08, 2007 CL New York Acad Med, New York, NY SP Assoc Res Nervous & Mental Dis HO New York Acad Med DE anesthesia; electroencephalogram; EEG; functional magnetic resonance imaging; fMRI ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; PROPOFOL ANESTHESIA; BURST SUPPRESSION; HUMANS; FMRI; METABOLISM; MECHANISMS; ISOFLURANE; EEG AB It has been long appreciated that anesthetic drugs induce stereotyped changes in electroencephalogram (EEG), but the relationships between the EEG and underlying brain function remain poorly understood. Functional imaging methods including positron emission tomography (PET) and functional magnetic resonance imaging (MRI), have become important tools for studying how anesthetic drugs act in the human brain to induce the state of general anesthesia. To date, no investigation has combined functional MRI with EEG to study general anesthesia. We report here a paradigm for conducting combined fMRI and EEG studies of human subjects under general anesthesia. We discuss the several technical and safety problems that must be solved to undertake this type of multimodal functional imaging and show combined recordings from a human subject. Combined fMRI and EEG exploits simultaneously the high spatial resolution of fMRI and the high temporal resolution of EEG. In addition, combined fMRI and EEG offers a direct way to relate established EEG patterns induced by general anesthesia to changes in neural activity in specific brain regions as measured by changes in fMRI blood oxygen level dependent (BOLD) signals. C1 [Purdon, Patrick L.; Pierce, Eric T.; Walsh, John; Harrell, P. Grace; Kwo, Jean; Merhar, Rebecca C.; Mullaly, Catherine M.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Purdon, Patrick L.; Bonmassar, Giorgio] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02114 USA. [Bonmassar, Giorgio] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Barlow, Margaret] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sullivan, Mary; Maginnis, Sharon; Skoniecki, Debra; Higgins, Helen-Anne] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. [Purdon, Patrick L.; Lamus, Camilo; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02114 USA. [Brown, Emery N.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02114 USA. [Deschler, Daniel] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Purdon, PL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Gary Bigelow 444, Boston, MA 02114 USA. EM patrickp@nmr.mgh.harvard.edu FU National Institutes of Health [DP1-OD003646, K25-NS05758, M01-RR-01066, RR02575801, R01-EB006385]; Massachusetts General Hospital Department of Anesthesia and Critical Care FX This work was supported by National Institutes of Health grants DP1-OD003646, K25-NS05758, M01-RR-01066, RR02575801, R01-EB006385, and the Massachusetts General Hospital Department of Anesthesia and Critical Care. NR 48 TC 25 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-743-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1157 BP 61 EP 70 DI 10.1111/j.1749-6632.2008.04119.x PG 10 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BJH38 UT WOS:000265826300006 PM 19351356 ER PT J AU Huang, YY Chen, ACH Carroll, JD Hamblin, MR AF Huang, Ying-Ying Chen, Aaron C. -H. Carroll, James D. Hamblin, Michael R. TI BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY SO DOSE-RESPONSE LA English DT Review ID ENERGY LASER IRRADIATION; HELIUM-NEON LASER; PLACEBO-CONTROLLED TRIALS; HUMAN SKIN FIBROBLASTS; REACTIVE OXYGEN; DOUBLE-BLIND; NITRIC-OXIDE; IN-VITRO; CELL-PROLIFERATION; MYOCARDIAL-INFARCTION AB The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01CA/AI838801, R01AI050875] FX Research in the Hamblin laboratory is supported by the US NIH ( grants R01CA/AI838801 and R01AI050875 to MRH). NR 109 TC 277 Z9 286 U1 2 U2 29 PU INT DOSE-RESPONSE SOC PI AMHERST PA UNIV MASSACHUSETTS SPH, MORRILL SCI CTR 1, N344, 639 N PLEASANT ST, AMHERST, MA 01003-9298 USA SN 1559-3258 J9 DOSE-RESPONSE JI Dose-Response PY 2009 VL 7 IS 4 BP 358 EP 383 DI 10.2203/dose-response.09-027.Hamblin PG 26 WC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology SC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology GA 527WT UT WOS:000272402400005 PM 20011653 ER PT J AU Suh, JJ Langleben, DD Ehrman, RN Hakun, JG Wang, Z Li, Y Busch, SI O'Brien, CP Childress, AR AF Suh, Jesse J. Langleben, Daniel D. Ehrman, Ronald N. Hakun, Jonathan G. Wang, Ze Li, Yin Busch, Samantha I. O'Brien, Charles P. Childress, Anna Rose TI Low prefrontal perfusion linked to depression symptoms in methadone-maintained opiate-dependent patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Opiate dependence; Depression; Methadone-maintenance; Affect regulation; Comorbidity; Prefrontal cortex ID CEREBRAL-BLOOD-FLOW; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; HAMILTON RATING-SCALE; MAJOR DEPRESSION; SUBSTANCE USE; COGNITIVE REGULATION; UNIPOLAR DEPRESSION; ANTERIOR CINGULATE; EXCHANGE PROGRAM; HEROIN USERS AB Background: Clinically depressed patients Without substance use disorders, compared to controls, exhibit significantly lower resting regional cerebral blood flow (rCBF) in the prefrontal cortex (PFC). In this study, we examined the link between resting rCBF in the PFC and current depressive symptoms in methadone-maintained opiate-dependent (MM) patients with or without major depression. Methods: Arterial spin labeled perfusion fMRI at 3 Tesla was used to measure resting rCBF in 21 MM patients. Per-fusion data were analyzed using SPM2. The relationship between Beck Depression Inventory (BDI) score and resting rCBF was examined in a single regression analysis. Results: The BDI scores ranged between 0 and 18 (m = 7.0, S.D. = 4.8), and 30% of the sample had mild to moderate depression symptoms according to BDI scores. A negative correlation was observed between BDI scores and relative rCBF in the bilateral ventrolateral prefrontal cortex, and middle frontal gyri. Conclusions: The inverse relationship between prefrontal paralimbic rCBF and depression Scores Suggests a link between reduced fronto-limbic activity and depressive symptoms in MM patients. A significant subgroup of opiate-dependent patients has clinical or sub-clinical depression that is often undetected; our data identify brain Substrates of depression symptoms that may also be a potential marker of relapse in this population. Treatment strategies targeting these brain regions may improve Outcomes in depressed Substance abusers. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Suh, Jesse J.; Langleben, Daniel D.; Ehrman, Ronald N.; Hakun, Jonathan G.; Wang, Ze; Li, Yin; Busch, Samantha I.; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Sch Med, Dept Psychiat, Ctr Studies Addict, Philadelphia, PA 19104 USA. [Langleben, Daniel D.; Ehrman, Ronald N.; O'Brien, Charles P.; Childress, Anna Rose] Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Suh, JJ (reprint author), Univ Penn, Sch Med, Dept Psychiat, Ctr Studies Addict, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM Suh_J@mail.trc.upenn.edu RI Wang, Ze/A-1043-2007; Langleben, Daniel/K-7407-2014 FU National Institute of Drug Abuse [T32 DA0724 1, K23 DAO 15746, RO1 DA10241, RO1 DA15149, P60 DA05186, P50 DA12756]; Veterans Affairs Medical Center-Philadelphia [VA VISN 4 MIRECC]; Alexander Foundation FX This study is supported by grants from the National Institute of Drug Abuse (T32 DA0724 1, K23 DAO 15746; RO1 DA10241, RO1 DA15149, P60 DA05186, P50 DA12756), the Veterans Affairs Medical Center-Philadelphia (VA VISN 4 MIRECC), and Alexander Foundation. NR 65 TC 3 Z9 7 U1 5 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2009 VL 99 IS 1-3 BP 11 EP 17 DI 10.1016/j.drugalcdep.2008.06.007 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 397ZH UT WOS:000262700500002 PM 18674871 ER PT J AU Howland, RH Rush, AJ Wisniewski, SR Trivedi, MH Warden, D Fava, M Davis, LL Balasubramani, GK McGrath, PJ Berman, SR AF Howland, Robert H. Rush, A. John Wisniewski, Stephen R. Trivedi, Madhukar H. Warden, Diane Fava, Maurizio Davis, Lori L. Balasubramani, G. K. McGrath, Patrick J. Berman, Susan R. TI Concurrent anxiety and substance use disorders among outpatients with major depression: Clinical features and effect on treatment outcome SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Depression; Major depression; Anxiety; Anxiety disorders; Comorbidity; Substance use disorders; Alcohol abuse; Drug abuse; Antidepressant treatment; Treatment outcome ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; ALCOHOL-USE DISORDERS; DIAGNOSTIC SCREENING QUESTIONNAIRE; COMORBIDITY SURVEY REPLICATION; NATIONAL EPIDEMIOLOGIC SURVEY; COMMUNITY MENTAL-HEALTH; ILLNESS RATING-SCALE; REPORT QIDS-SR; RELIEVE DEPRESSION AB Background: Depressed patients often present with comorbid anxiety and/or substance use disorder. This report compares the four groups defined by the disorders (anxiety disorder, substance use disorder, both, and neither) in terms of baseline clinical and sociodemographic features, and in terms of outcomes following treatment with citalopram (a selective serotonin reuptake inhibitor). Methods: The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial enrolled 2838 outpatients with non-psychotic major depressive disorder (MDD) from 18 primary and 23 psychiatric care clinics. Clinical and sociodemographic features were assessed at baseline. These baseline features and the treatment outcomes following treatment with citalopram were compared among the four groups. Results: Participants with non-psychotic MDD and comorbid anxiety and/or Substance use disorder showed several distinctive baseline sociodemographic and clinical features. They also showed greater depression severity; length of illness; likelihood of anxious, atypical or melancholic features; more intolerance/attrition; and worse remission/response outcomes with treatment. Participants with either anxiety or substance use disorder showed Outcomes generally intermediate between those with both and those with neither. Conclusions: Comorbid anxiety and/or Substance use disorder are clinically identifiable, and their presence may define distinct MDD subgroups that have more problems and worse pharmacological treatment Outcomes. They may benefit from more aggressive, multi-faceted treatment and psychosocial rehabilitation targeted at reducing their psychological comorbidity and functional impairment. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Howland, Robert H.; Berman, Susan R.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Rush, A. John; Trivedi, Madhukar H.; Warden, Diane] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Davis, Lori L.] Univ Alabama, VA Med Ctr 151, Tuscaloosa, AL 35404 USA. [McGrath, Patrick J.] Columbia Univ, New York, NY 10032 USA. [McGrath, Patrick J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Howland, RH (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. EM HowlandRH@upmc.edu RI McGrath, Patrick/I-6410-2013; Howland, Robert/K-6937-2015; OI McGrath, Patrick/0000-0001-7217-7321; Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU National Institute of Mental Health; National Institutes of Health [1MH90003] FX This project has been funded with Federal funds from the National Institute of Mental Health, National Institutes of Health, under Contract No. 1MH90003 to UT Southwestern Medical Center at Dallas (P.I.: A.J. Rush). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 72 TC 57 Z9 59 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2009 VL 99 IS 1-3 BP 248 EP 260 DI 10.1016/j.drugalcdep.2008.08.010 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 397ZH UT WOS:000262700500028 PM 18986774 ER PT J AU Farren, CK Scimeca, M Wu, R Malley, SO AF Farren, Conor K. Scimeca, Michael Wu, Ran Malley, Stephanie O. TI A double-blind, placebo-controlled study of sertraline with naltrexone for alcohol dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol dependence; Sertraline; Naltrexone; Clinical trial; Alcohol typology ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; DEPRESSED ALCOHOLICS; CLINICAL-EVIDENCE; DRINKING; FLUOXETINE; SEROTONIN; ABUSE; RATS; PHARMACOTHERAPY AB Introduction: Significant preclinical evidence exists for a synergistic interaction between the opioid and the serotonin systems in determining alcohol consumption. Naltrexone, an opiate receptor antagonist, is approved for the treatment of alcohol dependence. This double-blind placebo-controlled study examined whether the efficacy of naltrexone Would be augmented by Concurrent treatment with sertraline, a selective serotonin receptor uptake inhibitor (SSRI). Methods: One hundred and thirteen participants meeting DSM IV alcohol dependence criteria, who were abstinent from alcohol between 5 and 30 days, were randomly assigned to receive one of two treatments at two sites. One group received naltrexone 12.5 mg once daily for 3 days, 25 mg once daily for 4 days, and 50 mg once daily for the next 11 weeks, together with placebo sertraline. The other group received naltrexone as outlined and simultaneously received sertraline 50 mg once daily for 2 weeks, followed by 100 mg once daily for 10 weeks. Both groups received group relapse prevention psychotherapy on a weekly basis. Results: Compliance and attendance rates were comparable and high, The groups did not differ on the two primary outcomes, time to first drink and time to relapse to heavy drinking, or oil secondary treatment outcomes. With the exception of sexual side effects which were more common in the combination group, most adverse event, were similar for the two conditions. Conclusions: As the doses are tested in combination with specialized behavioral therapy, this study does not provide sufficient evidence for the combined use of sertraline and naltrexone above naltrexone alone. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Farren, Conor K.; Wu, Ran; Malley, Stephanie O.] Yale Univ, Sch Med, Dept Psychiat, Subst Abuse Treatment Unit, New Haven, CT 06419 USA. [Farren, Conor K.; Scimeca, Michael] Bronx Vet Adm Med Ctr, Mt Sinai Sch Med, Dept Psychiat, Bronx, NY 10468 USA. RP Farren, CK (reprint author), St Patricks Hosp, James St, Dublin 8, Ireland. EM cfarren@stpatsmail.com FU Mount Sinai GCRC [RO1AA11122, K05AA014715]; Pfizer Inc.; National Institutes of Health [RO1AA11122, K05AA014715]; State of Connecticut, Department of Mental Health and Addiction Services FX This study was supported by National Institutes of Health grants RO1AA11122, K05AA014715, by the Mount Sinai GCRC, and by the State of Connecticut, Department of Mental Health and Addiction Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Alcohol Abuse and Alcoholism or the National Institute of Health. NR 34 TC 11 Z9 13 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2009 VL 99 IS 1-3 BP 317 EP 321 DI 10.1016/j.drugalcdep.2008.06.006 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 397ZH UT WOS:000262700500034 PM 18644685 ER PT J AU Yong, PL Bigman, C Flynn, DN Mittermaier, D Long, JA AF Yong, Pierre L. Bigman, Cabral Flynn, David N. Mittermaier, Danielle Long, Judith A. TI Messages about Black-Box Warnings A Comparative Analysis of Reports from the FDA and Lay Media in the US SO DRUG SAFETY LA English DT Article ID PRESCRIPTION MEDICATIONS; NEWSPAPER COVERAGE; NEWS COVERAGE; BEHAVIOR; COMMUNICATION AB Background: The US FDA and lay media are important sources of information for the public about the risks of adverse events associated with drugs, yet the quality of FDA and US lay media reports about medication 'black-box' warnings, which highlight potentially severe adverse events from medications, is unknown. Objective: To determine and compare the content of FDA and US lay media reports about medication black-box warnings. Methods: We assessed FDA and US lay media reports about medication black-box warnings published or aired between I January 2003 and 31 December 2007 for the presence of six core message components, including (i) the affected drug's brand name; (ii) generic name; (iii) treatment indication; (iv) reason for the black-box warning; (v) clinical recommendations for patients, such as warning signs and symptoms of the adverse effect addressed by the black-box warning; and (vi) encouragement to discuss the issue with a healthcare provider, and additional characteristics. Results: FDA reports presented more core information than lay media reports (median 5 vs 3 message components; p < 0.001). FDA reports were more likely to mention generic names (84.6% vs 18.1%; p < 0.001) of affected drugs, while lay media reports less frequently detailed clinical recommendations for patients (43.9% vs 96.2%; p<0.001). Only 10.6% of lay media reports encouraged patients to seek additional information from their healthcare provider, compared with 48.1% of FDA reports (p < 0.001). Conclusions: FDA and US lay media reports about medication black-box warnings presented different information. This may reflect a difference in underlying motivation for reporting of news about risks of adverse drug events. It may also indicate a lack of agreement and understanding about the best methods to communicate risk information to the public, thus indicating areas for future research. C1 [Yong, Pierre L.] Univ Penn, Sch Med, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Yong, Pierre L.; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Yong, Pierre L.; Long, Judith A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Yong, Pierre L.] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Bigman, Cabral; Mittermaier, Danielle] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [Flynn, David N.; Long, Judith A.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Yong, PL (reprint author), Univ Penn, Sch Med, Robert Wood Johnson Clin Scholars Program, 1303A Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM pyong@nas.edu NR 30 TC 4 Z9 4 U1 1 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2009 VL 32 IS 12 BP 1147 EP 1157 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 531MM UT WOS:000272670400006 PM 19916582 ER PT J AU Patel, M AF Patel, Mukesh TI Community-Associated Meticillin-Resistant Staphylococcus aureus Infections Epidemiology, Recognition and Management SO DRUGS LA English DT Review ID ACQUIRED METHICILLIN-RESISTANT; PANTON-VALENTINE LEUKOCIDIN; SKIN-STRUCTURE INFECTIONS; INDUCIBLE CLINDAMYCIN RESISTANCE; CHROMOSOMAL CASSETTE MEC; SOFT-TISSUE INFECTIONS; MINIMUM INHIBITORY CONCENTRATION; VENTILATOR-ASSOCIATED PNEUMONIA; PROSTHETIC JOINT INFECTIONS; CARE-ASSOCIATED INFECTIONS AB Meticillin-resistant Staphylococcus aureus (MRSA) is an important cause of infection, particularly in hospitalized patients and those with significant healthcare exposure. In recent years, epidemic community-associated MRSA (CA-MRSA) infections occurring in patients without healthcare risk factors have become more frequent. The most common manifestation of CA-MRSA infection is skin and soft tissue infection, although necrotizing pneumonia, sepsis and osteoarticular infections can occur. CA-MRSA strains have become endemic in many communities and are genetically distinct from previously identified MRSA strains. CA-MRSA may be more capable colonizers of humans and more virulent than other S. aureus strains. Specific mechanisms of pathogenicity have not been elucidated, but several factors have been proposed as responsible for the virulence of CA-MRSA, including the Panton-Valentine leukocidin, phenol-soluble modulins and type I arginine catabolic mobile element. The movement of CA-MRSA strains into the nosocomial setting limits the utility of using clinical risk factors alone to designate community- or healthcare-associated status. Identification of unique genetic characteristics and genotyping are valuable tools for MRSA epidemiological studies. Although the optimum pharmacological therapy for CA-MRSA infections has not been determined, many CA-MRSA strains remain broadly susceptible to several non-p-lactam antibacterial agents. Empirical antibacterial therapy should include an MRSA-active agent, particularly in areas where CA-MRSA is endemic. C1 [Patel, Mukesh] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL 35294 USA. [Patel, Mukesh] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Patel, M (reprint author), Univ Alabama Birmingham, Div Infect Dis, THT 229,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mukesh@uab.edu NR 214 TC 25 Z9 28 U1 1 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 EI 1179-1950 J9 DRUGS JI Drugs PY 2009 VL 69 IS 6 BP 693 EP 716 PG 24 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 455WW UT WOS:000266800200004 PM 19405550 ER PT J AU Giraldez, RR Wiviott, SD Nicolau, JC Mohanavelu, S Morrow, DA Antman, EM Giugliano, RP AF Giraldez, Roberto R. Wiviott, Stephen D. Nicolau, Jose C. Mohanavelu, Satishkumar Morrow, David A. Antman, Elliott M. Giugliano, Robert P. TI Streptokinase and Enoxaparin as an Alternative to Fibrin-Specific Lytic-Based Regimens An ExTRACT-TIMI 25 Analysis SO DRUGS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TISSUE-PLASMINOGEN-ACTIVATOR; ST-SEGMENT ELEVATION; MOLECULAR-WEIGHT HEPARIN; ACUTE CORONARY SYNDROMES; RANDOMIZED-TRIAL; UNFRACTIONATED HEPARIN; THERAPY; REINFARCTION; MORTALITY AB Background: Enoxaparin was superior to unfractionated heparin (UFH), regardless of fibrinolytic agent in ST-elevation myocardial infarction (STEMI) patients receiving fibrinolytic therapy in ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment Thrombolysis in Myocardial Infarction 25) trial. Objective: This post hoc analysis compared outcomes with streptokinase plus enoxaparin to the standard regimen of fibrin-specific lytic (FSL) plus UFH and to the newer combination of FSL plus enoxaparin. Methods: In ExTRACT-TIMI 25, STEMI patients received either streptokinase or a FSL (alteplase, reteplase or tenecteplase) at the physician's discretion and were randomized to enoxaparin or UFH, stratified by fibrinolytic type. Thirty-day outcomes were adjusted for baseline characteristics, region, in-hospital percutaneous coronary intervention (PCI) and a propensity score for the choice of lytic. Results: The primary trial endpoint of 30-day death/myocardial infarction (MI) occurred in fewer patients in the streptokinase-enoxaparin cohort (n = 2083) compared with FSL-UFH (n = 8141) [10.2% vs 12.0%, adjusted odds ratio [OR(adj)] 0.76; 95% CI 0.62, 0.93; p = 0.008]. Major bleeding was significantly increased with streptokinase-enoxaparin compared with FSL-UFH (ORadj 2.74; 95% CI 1.81; 4.14; p < 0.001) but intracranial haemorrhage (ICH) was similar (OR(adj) 0.90; 95% CI 0.40, 2.01; p = 0.79). Net clinical outcomes, defined as either death/MI/major bleeding or as death/MI/ICH tended to favour streptokinase-enoxaparin compared with FSL-UFH (OR(adj) 0.88; 95% CI 0.73, 1.06; p = 0.17; and OR(adj) 0.77; 95% CI 0.63, 0.93; p = 0.008, respectively). Patients receiving FSL-enoxaparin (n = 8142) and streptokinase-enoxaparin therapies experienced similar adjusted rates of the primary endpoint (OR(adj) 1.08; 95% CI 0.87, 1.32; p = 0.49) and net clinical outcomes. Conclusions: Our results suggest that fibrinolytic therapy with the combination of streptokinase and the potent anticoagulant agent enoxaparin resulted in similar adjusted outcomes compared with more costly regimens utilizing a FSL. C1 [Giraldez, Roberto R.; Wiviott, Stephen D.; Mohanavelu, Satishkumar; Morrow, David A.; Antman, Elliott M.; Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Dept Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. [Nicolau, Jose C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. RP Giraldez, RR (reprint author), TIMI Study Off, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org RI Nicolau, Jose/E-1487-2012 NR 22 TC 4 Z9 5 U1 1 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2009 VL 69 IS 11 BP 1433 EP 1443 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 489RP UT WOS:000269440100003 PM 19634922 ER PT B AU Weinger, K Leighton, A AF Weinger, Katie Leighton, Ashley BE Weinger, K Carver, CA TI Living With Diabetes: The Role of Diabetes Education SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Education; Self-Care; Prevention; Diagnosis; Complications ID OF-THE-LITERATURE; RANDOMIZED CONTROLLED-TRIALS; SELF-MANAGEMENT EDUCATION; NATIONAL STANDARDS; INTENSIVE THERAPY; METABOLIC-CONTROL; META-ANALYSIS; INTERVENTIONS; METAANALYSIS; MELLITUS AB Living with diabetes can be challenging. The treatment is complex with significant lifestyle demands and fearsome acute and chronic complications. Both the disease and its treatment can impact the family as well as the person with diabetes. Many physicians, other health care professionals, and payors recognize the importance of diabetes education in supporting people in the efforts to realize treatment targets, yet the efficacy of diabetes education is still debated. This chapter will define diabetes education, briefly describe its origins, discuss factors that impact self-care, and address the question "does diabetes education work?" C1 [Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Weinger, K (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 50 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 3 EP 14 DI 10.1007/978-1-60327-208-7_1 D2 10.1007/978-1-60327-208-7 PG 12 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900001 ER PT B AU Carver, C Abrahamson, M AF Carver, Catherine Abrahamson, Martin BE Weinger, K Carver, CA TI Diabetes Mellitus Overview SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Insulin resistance; Pathophysiology; Cost; Complications; Diagnosis; Treatment; Self-care; Depression; Hypoglycemia; Self-management ID GLYCEMIC CONTROL; INSULIN THERAPY; LIFE-STYLE; SELF-CARE; MICROVASCULAR COMPLICATIONS; HIGH-PROTEIN; WEIGHT-GAIN; BODY-WEIGHT; TYPE-2; DEPRESSION AB Diabetes mellitus, the most common metabolic disorder affecting the population, has many clinical and psychological implications for the patient. The provider must address these issues comprehensively. This chapter will describe the global burden and cost of diabetes mellitus. define its classifications and diagnosis criteria, detail its current treatment options, address associated complications including depression, fear of hypoglycemia, and fear of weight gain, suggest strategies for healthy lifestyle changes, and illustrate the importance of the patient's self-care and empowerment. C1 [Carver, Catherine; Abrahamson, Martin] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Carver, C (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 52 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 15 EP 27 DI 10.1007/978-1-60327-208-7_2 D2 10.1007/978-1-60327-208-7 PG 13 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900002 ER PT B AU Campbell, AP Sullivan, ED AF Campbell, Amy P. Sullivan, Elaine D. BE Weinger, K Carver, CA TI Diabetes Education Process SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Assessment; Education plan; Goal setting; Readiness to learn; Documentation ID SELF-MANAGEMENT EDUCATION; NEWEST VITAL SIGN; CHRONIC ILLNESS; CHRONIC DISEASE; CARE; LITERACY; MODEL; PERFORMANCE; STANDARDS AB Diabetes self-management is well recognized as the cornerstone of a person's diabetes care. A person with diabetes must have the knowledge and skills to successfully manage his diabetes. The healthcare team is an integral part of a person's diabetes treatment plan. The team typically consists of a physician, a nurse educator, and a dietitian, although other healthcare providers may be part of the team, Such as an exercise physiologist, a pharmacist, and a mental health Counselor. The diabetes educator is primarily responsible for developing the patient's education plan with input from the patient, and support and reinforcement from the rest of the team. Individualized goal setting is a key component of the education plan and is essential to help the person with diabetes change behaviors to improve health and quality of life. The education plan is not static; it must be continually adjusted and updated to reflect the patient's changes in priorities and goals, the progression of diabetes, and life circumstances. Finally, the education plan must be appropriately documented in the patient's medical record to help monitor progress and to meet quality and accreditation standards. C1 [Campbell, Amy P.; Sullivan, Elaine D.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Campbell, AP (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 36 TC 0 Z9 0 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 45 EP 60 DI 10.1007/978-1-60327-208-7_4 D2 10.1007/978-1-60327-208-7 PG 16 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900004 ER PT B AU Mensing, C Hinnen, D AF Mensing, Carole Hinnen, Deborah BE Weinger, K Carver, CA TI Making the Most of the Outpatient Visit SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Outpatient Diabetes; Patient Education; Diabetes Self-Management Education; Outpatient Interdisciplinary Team Care ID TYPE-2 DIABETIC-PATIENTS; INSULIN THERAPY; HYPERGLYCEMIA; RISK; ROSIGLITAZONE; COMPLICATIONS; MANAGEMENT; RESISTANCE; TRIAL AB Primary care providers deliver more Outpatient diabetes management than any other group of health care professionals. However, primary care providers are faced with several challenges in providing diabetes education. Time restraints, high patient volumes, and other medical issues that Must be addressed are just some of the many factors that may impede effective diabetes education. Solutions to these issues include involving the entire outpatient office staff in the diabetes management of the patient; focusing on issues of most concern to the patient; providing basic, "survival" skill education; and referring, when appropriate, to other specialists, including endocrinologists and diabetes educators. C1 [Mensing, Carole] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hinnen, Deborah] Mid Amer Diabet Associates, Wichita, KS USA. RP Mensing, C (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 61 EP 80 DI 10.1007/978-1-60327-208-7_5 D2 10.1007/978-1-60327-208-7 PG 20 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900005 ER PT B AU Millan-Ferro, A Caballero, E AF Millan-Ferro, Andreina Caballero, Enrique BE Weinger, K Carver, CA TI Role of Culture and Health Literacy in Diabetes Self-Management and Education SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Culture; Health literacy; Diabetes; Cultural competence; Minority groups ID MEXICAN-AMERICANS; UNITED-STATES; PRIMARY-CARE; DISEASE MANAGEMENT; INSULIN THERAPY; ADULTS; ACCULTURATION; BARRIERS; FAMILY; DEPRESSION AB To educate patients with diabetes in a multicultural society presents educators with the challenge of becoming culturally sensitive in order to understand and convey the meaning of untranslatable education messages for patients of all health literacy levels. The goal of this chapter is to raise awareness about the most common cultural and social factors. that may influence diabetes self-care management and education in patients from culturally diverse populations. C1 [Millan-Ferro, Andreina; Caballero, Enrique] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Millan-Ferro, A (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 58 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 115 EP 134 DI 10.1007/978-1-60327-208-7_8 D2 10.1007/978-1-60327-208-7 PG 20 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900008 ER PT B AU Hsu, WC Wolpert, HA AF Hsu, William C. Wolpert, Howard A. BE Weinger, K Carver, CA TI Technology in Self-Care: Implications for Diabetes Education SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Continuous Glucose Monitors (CGM); Continuous Subcutaneous Insulin Infusion (CSII); Diabetes Technology ID SUBCUTANEOUS INSULIN INFUSION; INDUCED HYPOGLYCEMIA; PUMP THERAPY; METAANALYSIS AB New diabetes technologies, such as insulin pump therapies and continuous glucose monitors (CGM), have become important tools for helping control hypoglycemia and achieving glycemic targets. There are, of course, advantages and disadvantages to the adoption of these technological tools, and patients require mastery of new skills in order to use these tools Successfully. For the patient, use of the new technologies can be overwhelming or extremely helpful, which often depends on one's level of knowledge about the new tools. Therefore, this chapter provides the basic foundation for educating patients about these new diabetes technologies. C1 [Hsu, William C.; Wolpert, Howard A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Hsu, WC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 135 EP 141 DI 10.1007/978-1-60327-208-7_9 D2 10.1007/978-1-60327-208-7 PG 7 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900009 ER PT B AU Maryniuk, MD Goodwin, JE AF Maryniuk, Melinda D. Goodwin, Judith E. BE Weinger, K Carver, CA TI Diabetes Education Program Evaluation: Ensuring Effective Operations SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Program Evaluation; Clinical Evaluation; Operational Evaluation; Operational Metrics; Pro Forma; Productivity; Satisfaction; Continuous Quality Improvement ID SELF-MANAGEMENT EDUCATION AB The effectiveness of a diabetes education program is evaluated not only in clinical terms but also in operational terms. Each program needs to be routinely assessed in order for it to be considered comprehensive. This chapter will highlight the rationale for program evaluation, recommend how to use a variety of metrics to assess program impact, and provide practical suggestions for ways to help demonstrate the value of a diabetes education program. C1 [Maryniuk, Melinda D.; Goodwin, Judith E.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Maryniuk, MD (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 177 EP 193 DI 10.1007/978-1-60327-208-7_12 D2 10.1007/978-1-60327-208-7 PG 17 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900012 ER PT B AU Ritholz, MD AF Ritholz, Marilyn D. BE Weinger, K Carver, CA TI Working with Challenging Patients in Diabetes Treatment SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Challenging patients; Working alliance; type 1 and type 2 diabetes; Psychosocial problems; Fear of hypoglycemia; Fear of hyperglycemia; Fear of weight gain; Depression; co-morbid chronic conditions ID DEPRESSIVE SYMPTOMS; EATING-DISORDERS; CLINICAL PREDICTORS; ANXIETY DISORDERS; DIFFICULT PATIENT; COMPETING DEMANDS; MAJOR DEPRESSION; INSULIN OMISSION; GLYCEMIC CONTROL; MEDICAL-CARE AB Patients in diabetes treatment sometimes struggle with psychosocial problems that may interact with their abilities to manage diabetes. Health care providers may feet frustrated, ineffective, and helpless because it is difficult to form a working alliance with these challenging patients. This chapter defines the working alliance and presents it as an essential ingredient of patient-centered diabetes treatment and as a salient factor in counteracting challenging patient encounters. It also reviews the literature on fear-based psychosocial problems in relation to hypoglycemia, hyperglycemia, or weight gain as well as co-morbid conditions of diabetes, depression, and other chronic illnesses. This chapter also discusses the ways these conditions contribute to challenging patient encounters and presents clinical vignettes to illustrate the dynamics and complexities of working with these psychosocial difficulties. Finally, suggestions are offered on ways to build a working alliance with patients in challenging patient encounters. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Ritholz, MD (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 68 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 197 EP 212 DI 10.1007/978-1-60327-208-7_13 D2 10.1007/978-1-60327-208-7 PG 16 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900013 ER PT B AU Halprin, ES AF Halprin, Elizabeth S. BE Weinger, K Carver, CA TI Diabetes in Pregnancy SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE diabetes; pregnancy; gestational diabetes; preconception counseling; glucose management ID CONGENITAL-MALFORMATIONS; FETAL HYPERINSULINISM; PREPREGNANCY CARE; METABOLIC-CONTROL; WOMEN; MELLITUS; MOTHERS; MANAGEMENT; OUTCOMES; INSULIN AB A review of present practices in the assessment and treatment of diabetes during pregnancy is presented, including preconception counseling, insulin therapy, nutrition and exercise therapy of patients with pre-existing diabetes, care of patients with gestational diabetes, and post-partum care for infants and mothers of both conditions. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Halprin, ES (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 62 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 235 EP 250 DI 10.1007/978-1-60327-208-7_15 D2 10.1007/978-1-60327-208-7 PG 16 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900015 ER PT B AU Smaldone, A Lawlor, MT AF Smaldone, Arlene Lawlor, Margaret T. BE Weinger, K Carver, CA TI Pediatric Diabetes Education: A Family Affair SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Diabetes; Children; Adolescents; Family; School; Camp; Depression; Eating disorders ID INSULIN PUMP THERAPY; QUALITY-OF-LIFE; GLYCEMIC CONTROL; METABOLIC-CONTROL; EATING-DISORDERS; MICROVASCULAR COMPLICATIONS; PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; ADOLESCENT FEMALES; COLLEGE-STUDENTS AB Implementation of findings of the Diabetes Control and Complications Trial (DCCT) has dramatically changed diabetes care for pediatric patients. The purpose of this chapter, within the broader scope of this book, is to examine unique issues in caring for children and adolescents with diabetes and provide a synopsis of current clinical practice and research findings relevant to care of this population. Normative aspects of growth and development provide background to the need for tailoring diabetes education and self-care expectations according to a child's age and developmental stage. The role of the diabetes educator working with children and families during specific transition points through childhood is examined: school issues, camping diabetes style, adolescence, and transition to young adulthood. C1 [Smaldone, Arlene] Columbia Univ, Sch Nursing, New York, NY 10027 USA. [Lawlor, Margaret T.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Smaldone, A (reprint author), Columbia Univ, Sch Nursing, New York, NY 10027 USA. NR 96 TC 2 Z9 2 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 251 EP 271 DI 10.1007/978-1-60327-208-7_16 D2 10.1007/978-1-60327-208-7 PG 21 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900016 ER PT B AU Goebel-Fabbri, AE Arathuzik, GG Shahar, JI AF Goebel-Fabbri, Ann E. Arathuzik, Gillian Grant Shahar, Jacqueline I. BE Weinger, K Carver, CA TI The Challenge of Weight and Diabetes Management in Clinical Practice SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Lifestyle approach; Behavioral weight loss; Exercise; Obesity; Nutrition ID LIFE-STYLE INTERVENTION; BLOOD-GLUCOSE CONTROL; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; GLYCEMIC CONTROL; TYPE-2; OBESITY; RISK; COMPLICATIONS AB Behavioral approaches to weight loss and diabetes management have been studied for decades. Effective lifestyle programs successfully combine three primary interventions-dietary changes, increased physical activity, and behavioral weight loss strategies. The goal of such a multi-pronged approach is to teach patients the skills they need to maintain a balanced meal plan, a long-term exercise program, and integrate these new habits with cognitive and behavioral principles tailored to their unique potential triggers for relapse. The treatment ideal would consist of a comprehensive and multi-disciplinary diabetes team. Without access to Such a team, these interventions require clinicians to be familiar with behavioral weight loss techniques, nutrition recommendations, and exercise goals for weight and diabetes management. The principles outlined here are intended to provide practical, empirically supported techniques for improving diabetes and weight-related wellness in this burgeoning patient population. C1 [Goebel-Fabbri, Ann E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Goebel-Fabbri, AE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 273 EP 287 DI 10.1007/978-1-60327-208-7_17 D2 10.1007/978-1-60327-208-7 PG 15 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900017 ER PT B AU Botts, A Munshi, M AF Botts, Angela Munshi, Medha BE Weinger, K Carver, CA TI Diabetes Education in Geriatric Populations SO EDUCATING YOUR PATIENT WITH DIABETES SE Contemporary Diabetes LA English DT Article; Book Chapter DE Diabetes education; Geriatric; Elderly; Barriers to self-care ID RANDOMIZED CONTROLLED-TRIAL; FUNCTIONAL HEALTH LITERACY; OLDER-ADULTS; DEPRESSIVE SYMPTOMS; COGNITIVE IMPAIRMENT; GLYCEMIC CONTROL; SELF-CARE; PHYSICAL-DISABILITY; ELDERLY PATIENTS; DRUG-THERAPY AB The population in the United States, as well as all around the world, is aging rapidly. The management of the chronic diseases in this elderly population is challenging and requires a different approach when compared to Younger adults. Diabetes in particular has increasing prevalence in elderly patients. Challenges and barriers to self-care are unique in elderly patients with diabetes. Education that addresses these needs and takes into account the geriatric-specific barriers is important for better control of diabetes and overall quality of life in this population. This chapter focuses on unique challenges faced by elderly patients with diabetes and the importance of customizing education strategies based on such issues. C1 [Botts, Angela; Munshi, Medha] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Botts, A (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 77 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-207-0 J9 CONTEMP DIABETES PY 2009 BP 289 EP 307 DI 10.1007/978-1-60327-208-7_18 D2 10.1007/978-1-60327-208-7 PG 19 WC Endocrinology & Metabolism; Medicine, General & Internal; Nursing SC Endocrinology & Metabolism; General & Internal Medicine; Nursing GA BJT65 UT WOS:000267138900018 ER PT B AU Rottmann, J Aristophanous, M Park, SJ Chen, A Berbeco, R AF Rottmann, Joerg Aristophanous, Michalis Park, Sang-June Chen, Aileen Berbeco, Ross BE Wani, MA Kantardzic, M Palade, V Kurgan, L Qi, Y TI Multi-region tracking for lung tumor motion assessment SO EIGHTH INTERNATIONAL CONFERENCE ON MACHINE LEARNING AND APPLICATIONS, PROCEEDINGS LA English DT Proceedings Paper CT 8th International Conference on Machine Learning and Applications CY DEC 13-15, 2009 CL Miami Beach, FL SP IEEE SMCS, Cal State Univ, Assoc Machine Learning & Appl, Univ Louisville ID STEREOTACTIC BODY RADIOTHERAPY; CINE MODE; IMAGES; VERIFICATION; FEASIBILITY; MARKERS AB There is a need for a method of tracking lung tumors in beam's-eye-view MV image sequences without implanted radiopaque fiducials. We present a multi-region tracking algorithm to follow lung tumors on CT projections and in-treatment portal image movies before and during external beam radiotherapy, respectively. Finding suitable landmarks for tracking is challenging due to low contrast in the images. We begin by defining a large set of landmark candidates and a sequence of training images representing the range of tumor motion. Each landmark is found automatically by seeking regions of maximum variance in the image gray values. Small, square templates are centered around each landmark to be used for tracking in sequential MV images. An iterative learning algorithm is employed to select the most suitable templates among the large collection of candidates for the training data set. This subset of templates is then applied to a similar data set for testing. The results of the automatic multi-template selection and tracking compare well to those of manually selected single template tracking. The algorithm shows great promise as a technique for automatically tracking lung tumors in beam's-eye-view in-treatment images without the need for implanted radiopaque fiducials. C1 [Rottmann, Joerg; Aristophanous, Michalis; Park, Sang-June; Chen, Aileen; Berbeco, Ross] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St L2, Boston, MA 02115 USA. RP Rottmann, J (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St L2, Boston, MA 02115 USA. EM jrottmann@lroc.harvard.edu OI Chen, Aileen/0000-0002-5385-3360 NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3926-3 PY 2009 BP 489 EP + DI 10.1109/ICMLA.2009.125 PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BVC15 UT WOS:000291011600074 ER PT J AU Gazdag, G Mann, SC Ungvari, GS Caroff, SN AF Gazdag, Gabor Mann, Stephan C. Ungvari, Gabor S. Caroff, Stanley N. BE Swartz, CM TI Clinical evidence for the efficacy of electroconvulsive therapy in the treatment of catatonia and psychoses SO ELECTROCONVULSIVE AND NEUROMODULATION THERAPIES LA English DT Article; Book Chapter ID LIFE-THREATENING CATATONIA; SCHIZOAFFECTIVE DISORDER; ELDERLY-PATIENTS; LETHAL CATATONIA; 1ST-EPISODE SCHIZOPHRENIA; REFRACTORY SCHIZOPHRENIA; MALIGNANT CATATONIA; CONVULSIVE THERAPY; ORGANIC CATATONIA; MANIC EPISODES C1 [Gazdag, Gabor] Jahn Ferenc Hosp, Inpatient Sect, Dept Psychiat, Budapest, Hungary. [Mann, Stephan C.] Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA. [Mann, Stephan C.] Cent Montgomery Mental Hlth & Mental Retardat Ctr, Norristown, PA USA. [Ungvari, Gabor S.] Chinese Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Ungvari, Gabor S.] Shatin Hosp, Dept Psychiat, Shatin, Hong Kong, Peoples R China. [Caroff, Stanley N.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Caroff, Stanley N.] Vet Affairs Med Ctr, Inpatient Sect, Behav Hlth Serv, Philadelphia, PA USA. RP Gazdag, G (reprint author), Jahn Ferenc Hosp, Inpatient Sect, Dept Psychiat, Budapest, Hungary. NR 122 TC 4 Z9 4 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88388-7 PY 2009 BP 124 EP 148 DI 10.1017/CBO9780511576393.008 D2 10.1017/CBO9780511576393 PG 25 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BDX12 UT WOS:000315519200008 ER PT J AU Zhao, B Benson, EK Qiao, RF Wang, X Kim, SC Manfredi, JJ Lee, SW Aaronson, SA AF Zhao, Bo Benson, Erica K. Qiao, Ruifang Wang, Xing Kim, Sunchin Manfredi, James J. Lee, Sam W. Aaronson, Stuart A. TI Cellular senescence and organismal ageing in the absence of p21(CIP1/WAF1) in ku80(-/-) mice SO EMBO REPORTS LA English DT Article DE ageing; cellular senescence; Ku80; p21; p53 ID DNA-DAMAGE; REPLICATIVE SENESCENCE; V(D)J RECOMBINATION; RAG-1-INDUCED DSBS; MURINE FIBROBLASTS; LIFE-SPAN; P53; CELLS; DELETION; ARREST AB Ku80 is important in the repair of DNA double-strand breaks by its essential function in non-homologous end-joining. The absence of Ku80 causes the accumulation of DNA damage and leads to premature ageing in mice. We showed that mouse embryonic fibroblasts (MEFs) from ku80(-/-) mice senesced rapidly with elevated levels of p53 and p21. Deletion of p21 delayed the early senescence phenotype in ku80(-/-) MEFs, despite an otherwise intact response of p53. In contrast to ku80(-/-)p53(-/-) mice, which die rapidly primarily from lymphomas, there was no significant increase in tumorigenesis in ku80(-/-)p21(-/-) mice. However, ku80(-/-)p21(-/-) mice showed no improvement with respect to rough fur coat or osteopaenia, and even showed a shortened lifespan compared with ku80(-/-) mice. These results show that the increased lifespan of ku80(-/-) MEFs owing to the loss of p21 is not associated with an improvement of the premature ageing phenotypes of ku80(-/-) mice observed at the organismal level. C1 [Zhao, Bo; Benson, Erica K.; Qiao, Ruifang; Wang, Xing; Kim, Sunchin; Manfredi, James J.; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Aaronson, SA (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, Gustave L Levy Pl,POB 1130, New York, NY 10029 USA. EM stuart.aaronson@mssm.edu FU National Institute of Health [5R01CA085214, 5P01CA080058, 1R01CA127247, 2R01CA085681] FX We thank Salvador Macip and Shen Yao for technical advice, and Alka Mahale for help with initial genotypings of the Ku80+/- mouse colony. This study was supported by National Institute of Health grants 5R01CA085214 and 5P01CA080058 (to S. A. A.), 1R01CA127247 and 2R01CA085681 (to S. W. L). NR 31 TC 19 Z9 20 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JAN PY 2009 VL 10 IS 1 BP 71 EP 78 DI 10.1038/embor.2008.220 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 387ER UT WOS:000261935000015 PM 19079133 ER PT J AU Hutson, HR Anglin, D Rice, P Kyriacou, DN Guirguis, M Strote, J AF Hutson, H. R. Anglin, D. Rice, P. Kyriacou, D. N. Guirguis, M. Strote, J. TI Excessive use of force by police: a survey of academic emergency physicians SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID INTIMATE PARTNER VIOLENCE; IDENTIFICATION; MANAGEMENT; NURSES AB Objective: To determine the clinical experience, management and training of emergency physicians in the suspected use of excessive force by law enforcement officers. Methods: Surveys were mailed to a random sample of academic emergency physicians in the USA. Results: Of 393 emergency physicians surveyed, 315 (80.2%) responded. Of the respondents, 99.8% (95% CI 98.2% to 100.0%) believed excessive use of force actually occurs and 97.8% (95% CI 95.5% to 99.1%) replied that they had managed patients with suspected excessive use of force. These incidents were not reported by 71.2% (95% CI 65.6% to 76.4%) of respondents, 96.5% (95% CI 93.8% to 98.2%) had no departmental policies and 93.7% (95% CI 90.4% to 96.1%) had not received training in the management of these cases. Conclusions: Suspected excessive use of force is encountered by academic emergency physicians in the USA. There is only limited training or policies for the management of these cases. C1 [Strote, J.] Univ Washington, Med Ctr, Div Emergency Med, Seattle, WA 98195 USA. [Hutson, H. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Anglin, D.] Univ So Calif, Keck Sch Med, Dept Emergency Med, Los Angeles, CA 90033 USA. [Rice, P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Kyriacou, D. N.] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Guirguis, M.] Kaiser Permanente Fontana, Fontana, CA USA. RP Strote, J (reprint author), Univ Washington, Med Ctr, Div Emergency Med, Box 356123,1959 NE Pacific St, Seattle, WA 98195 USA. EM strote@u.washington.edu NR 17 TC 14 Z9 14 U1 1 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 J9 EMERG MED J JI Emerg. Med. J. PD JAN PY 2009 VL 26 IS 1 BP 20 EP 22 DI 10.1136/emj.2007.053348 PG 3 WC Emergency Medicine SC Emergency Medicine GA 393SX UT WOS:000262394300007 PM 19104090 ER PT J AU Harrington, AT Castellanos, JA Ziedalski, TM Clarridge, JE Cookson, BT AF Harrington, Amanda T. Castellanos, Jaime A. Ziedalski, Tomasz M. Clarridge, Jill E., III Cookson, Brad T. TI Isolation of Bordetella avium and Novel Bordetella Strain from Patients with Respiratory Disease SO EMERGING INFECTIOUS DISEASES LA English DT Article ID BRONCHISEPTICA AB Bordetella avium is thought to be strictly an avian pathogen. However, 16S rRNA gene sequencing identified 2 isolates from 2 humans with respiratory disease as B. avium and a novel B. avium-like strain. Thus, B. avium and B. avium-like organisms are rare opportunistic human pathogens.. C1 [Harrington, Amanda T.; Clarridge, Jill E., III; Cookson, Brad T.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Clarridge, Jill E., III] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Castellanos, Jaime A.] Baylor Coll Med, Houston, TX 77030 USA. [Ziedalski, Tomasz M.] Western Washington Med Grp, Everett, WA USA. RP Cookson, BT (reprint author), Univ Washington, Dept Lab Med, Box 357110,1959 NE Pacific St, Seattle, WA 98195 USA. EM cookson@u.washington.edu NR 7 TC 17 Z9 20 U1 0 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2009 VL 15 IS 1 BP 72 EP 74 DI 10.3201/eid1501.071677 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 393AG UT WOS:000262342700016 PM 19116056 ER PT J AU Houser, CR AF Houser, C. R. BE Schwartzkroin, PA TI Plasticity and Reorganization of GABA Neurons in Epilepsy SO ENCYCLOPEDIA OF BASIC EPILEPSY RESEARCH, VOLS 1-3 LA English DT Article; Book Chapter ID TEMPORAL-LOBE EPILEPSY; SPONTANEOUS RECURRENT SEIZURES; GABAERGIC INTERNEURONS; PILOCARPINE MODEL; MOUSE MODEL; VULNERABILITY; HIPPOCAMPUS; RECEPTORS; SYSTEM C1 [Houser, C. R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Houser, C. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-373961-2 PY 2009 BP 619 EP 625 PG 7 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA BFJ85 UT WOS:000320162800106 ER PT J AU Cole, AJ AF Cole, A. J. BE Schwartzkroin, PA TI Seizure-Induced Injury and the Two-Hit Hypothesis SO ENCYCLOPEDIA OF BASIC EPILEPSY RESEARCH, VOLS 1-3 LA English DT Article; Book Chapter ID INDUCED BRAIN-INJURY; RAT-BRAIN; EPILEPTOGENESIS; SUSCEPTIBILITY; HIPPOCAMPUS; NEURONS; SYSTEM C1 [Cole, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cole, A. J.] Harvard Univ, Sch Med, Boston, MA USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-373961-2 PY 2009 BP 1075 EP 1078 PG 4 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA BFJ85 UT WOS:000320162800184 ER PT J AU Staley, K AF Staley, K. BE Schwartzkroin, PA TI Neuronal Cl Transport: Setting the Stage for Successful Inhibition SO ENCYCLOPEDIA OF BASIC EPILEPSY RESEARCH, VOLS 1-3 LA English DT Article; Book Chapter ID TEMPORAL-LOBE EPILEPSY; CHLORIDE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Staley, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-373961-2 PY 2009 BP 1405 EP 1409 PG 5 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA BFJ85 UT WOS:000320162800238 ER PT J AU Cole, AJ AF Cole, A. J. BE Schwartzkroin, PA TI Seizure-Related Acute MRI Changes SO ENCYCLOPEDIA OF BASIC EPILEPSY RESEARCH, VOLS 1-3 LA English DT Article; Book Chapter ID POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; FOCAL STATUS EPILEPTICUS; CORPUS-CALLOSUM; DIFFUSION; SPLENIUM; EPILEPSY; LESION; BRAIN C1 [Cole, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cole, A. J.] Harvard Univ, Sch Med, Boston, MA USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-373961-2 PY 2009 BP 1573 EP 1579 PG 7 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA BFJ85 UT WOS:000320162800265 ER PT B AU Gillick, MR Volandes, AE AF Gillick, Muriel R. Volandes, Angelo E. BE Murphy, D Longo, D TI THE PSYCHOLOGY OF USING AND CREATING VIDEO DECISION AIDS FOR ADVANCE CARE PLANNING SO ENCYCLOPEDIA OF PSYCHOLOGY OF DECISION MAKING LA English DT Article; Book Chapter DE Advance Care Planning; Decision Making; Video Decision Aids; Patient-Physician Communication; Dementia; Health Literacy ID CONTROLLED-TRIAL; DISEASE AB Decision-making in the medical context has traditionally focused on individual patients choosing between various medical treatments that have been proposed for an acute medical problem. For example, a pregnant woman may need to decide whether or not to undergo amniocentesis to rule out Down's syndrome in her fetus, or a man with all elevated prostate specific antigen test may need to choose between "watchful waiting" or radical prostate surgery. Much of this research has focused oil how patients process information and how physicians call objectively present such information to improve decision-making. Advance care planning is the process in which patients plan for their future medical care. Patients asked to consider the benefits and burdens of various interventions that might be considered for some hypothetical disease state, such as dementia. Advance care planning is advocated largely in order ensure that the treatment the patient receives is consistent with his own preferences-even if he is incapable of making decisions at the time of illness. While advocated on theoretical grounds, advance care planning has not been widely adopted, either by patients or physicians. A major barrier to engaging in advance care planning is that patients are often unfamiliar both with the hypothetical disease state and with the specific medical interventions that might be used to treat them. Video has previously been used as a decision aid for patients facing real time decisions about their medical care. The application of video to advance care planning discussions is a new approach that has the potential to help surmount the barrier to informed decision making. Video is a powerful and widely accessible medium that engages patients in a way not easily captured with words. Video allows patients to imagine hypothetical health states and can provide an accurate portrayal of medical interventions. This chapter will review the emerging corpus of work that uses video as an adjunct to advance care planning, specifically in planning for the possible development of dementia. It will analyze the biases that can arise from the use of an aesthetic and visual medium and discuss ways those biases can be avoided. The chapter will make the case that video is useful for patients with low health literacy and patients from minority populations. Finally, other specific disease entities that lend themselves to video portraits will be proposed. C1 [Gillick, Muriel R.] Harvard Univ, Sch Med, Harvard Pilgrim & Harvard Vanguard Med Associates, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02215 USA. RP Gillick, MR (reprint author), Harvard Univ, Sch Med, Harvard Pilgrim & Harvard Vanguard Med Associates, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM mgillick@partners.org; avolandes@partners.org NR 24 TC 0 Z9 0 U1 1 U2 2 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60692-160-9 PY 2009 BP 183 EP 196 PG 14 WC Business; Economics; Psychology, Applied; Social Sciences, Interdisciplinary SC Business & Economics; Psychology; Social Sciences - Other Topics GA BNU77 UT WOS:000275614100013 ER PT J AU Davies, TF Latif, R Yin, XM AF Davies, Terry F. Latif, Rauf Yin, Xiaoming TI INHERITING AUTOIMMUNE THYROID DISEASE SO ENDOCRINE PRACTICE LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; GRAVES-DISEASE; SUSCEPTIBILITY LOCI; HASHIMOTOS-THYROIDITIS; GENETIC-HETEROGENEITY; WHICKHAM SURVEY; FAMILIES; PEROXIDASE; HLA; AUTOANTIBODIES C1 [Davies, Terry F.; Latif, Rauf; Yin, Xiaoming] James J Peters VA Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, New York, NY USA. RP Davies, TF (reprint author), Mt Sinai Med Ctr, Box 1055,1 Gustave L Levy Pl, New York, NY 10029 USA. EM terry.davies@mssm.edu FU NIDDK NIH HHS [DK052464, DK069713] NR 26 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD JAN-FEB PY 2009 VL 15 IS 1 BP 63 EP 66 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 437NO UT WOS:000265494400014 PM 19211403 ER PT J AU Bokov, AF Ko, DJ Richardson, A AF Bokov, Alex F. Ko, Daijin Richardson, Arlan TI The Effect Of Gonadectomy And Estradiol On Sensitivity To Oxidative Stress SO ENDOCRINE RESEARCH LA English DT Review DE Estradiol; Paraquat; Oxidative Stress; Mice; Gonadectomy ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; ERYTHROCYTE GLUTATHIONE-PEROXIDASE; DISMUTASE MIMETIC PROTECTS; HEALTH INITIATIVE MEMORY; CORONARY HEART-DISEASE; INDUCED LUNG INJURY; POSTMENOPAUSAL WOMEN; PARAQUAT TOXICITY; SUPEROXIDE-DISMUTASE AB The sexual dimorphism of life span and caloric restriction effects in numerous species suggest that estradiol (E2) is protective against oxidative damage. The only direct test of E2's protective effect in mice against in vivo oxidative stress to date may have been confounded by E2's direct chemical action as an antioxidant because it was administered at very high dosages. Therefore, we have identified a low yet physiologically effective dose of E2. We then administered this dose using subcutaneous time-release pellets to ovariectomized mice. Two weeks after E2 pellet implantation, sham-operated, ovariectomized, and ovariectomized E2-supplemented female mice were injected with a lethal dose of paraquat and their survival was followed. It was observed that ovariectomy exacerbates paraquat-induced mortality and is rescued by E2 supplementation. An equivalent experiment was performed on sham-operated, orchidectomized, and E2-supplemented orchidectomized male mice. The survival of male mice was improved by orchidectomy, and E2 gave no further benefit. We interpret the results to mean that E2 is protective against oxidative stress through its regulatory role and that testosterone diminishes protection against oxidative stress. C1 [Bokov, Alex F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Ko, Daijin] Univ Texas San Antonio, Coll Business, Dept Management Sci & Stat, San Antonio, TX USA. [Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Richardson, Arlan] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Bokov, AF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM bokov@uthscsa.edu FU National Institutes of Health [AGO-21890, AG-19316, AG-13319, AG-23843, AG-26557]; San Antonio Nathan Shock Aging Center [1P30-AG13319]; Department of Veterans Affairs Merit Grant; Research Enhancement Award Program; Department of Veterans Affairs FX The authors gratefully acknowledge support from the National Institutes of Health: AGO-21890 (A. F. B); AG-19316, AG-13319, AG-23843, and AG-26557 (A. R.); the San Antonio Nathan Shock Aging Center (1P30-AG13319) (A. R.); Department of Veterans Affairs Merit Grant (A. R.); and a Research Enhancement Award Program from the Department of Veterans Affairs (A. R.) NR 117 TC 9 Z9 9 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0743-5800 EI 1532-4206 J9 ENDOCR RES JI Endocr. Res. PY 2009 VL 34 IS 1-2 BP 43 EP 58 AR PII 910860504 DI 10.1080/07435800902913600 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QO UT WOS:000267370900005 PM 19557590 ER PT B AU Nucera, C Parker, JA Parangi, S AF Nucera, Carmelo Parker, J. Anthony Parangi, Sareh BE Hubbard, JGH Inabnet, WB Lo, CY TI Thyroid Imaging SO ENDOCRINE SURGERY: PRINCIPLES AND PRACTICE SE Springer Specialist Surgery Series LA English DT Article; Book Chapter ID FINE-NEEDLE-ASPIRATION; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASES; SERUM THYROGLOBULIN MEASUREMENT; FLOW DOPPLER SONOGRAPHY; LOW-RISK PATIENTS; FOLLOW-UP; COMPUTED-TOMOGRAPHY; GRAVES-DISEASE; CONGENITAL HYPOTHYROIDISM C1 [Nucera, Carmelo; Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen & Gastrointestinal Surg,Dept Surg, Boston, MA 02115 USA. [Parker, J. Anthony] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Nucl Med, Boston, MA 02215 USA. RP Nucera, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen & Gastrointestinal Surg,Dept Surg, Boston, MA 02115 USA. NR 121 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84628-880-7 J9 SPRINGER SPEC SURG S PY 2009 BP 49 EP 68 DI 10.1007/978-1-84628-881-4_4 D2 10.1007/978-1-84628-881-4 PG 20 WC Endocrinology & Metabolism; Surgery SC Endocrinology & Metabolism; Surgery GA BKO03 UT WOS:000268741400004 ER PT B AU Lesnik, DJ Randolph, GW AF Lesnik, David J. Randolph, Gregory W. BE Hubbard, JGH Inabnet, WB Lo, CY TI Management of the Laryngeal Nerves and Voice SO ENDOCRINE SURGERY: PRINCIPLES AND PRACTICE SE Springer Specialist Surgery Series LA English DT Article; Book Chapter ID VOCAL CORD PARALYSIS; THYROID-SURGERY; PARATHYROID SURGERY; SWALLOWING CHANGES; FOLD PARALYSIS; SINGING VOICE; INJURY; DYSPHONIA; ELECTROMYOGRAPHY; IDENTIFICATION C1 [Lesnik, David J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol & Head & Neck Surg, Boston, MA USA. RP Lesnik, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 68 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84628-880-7 J9 SPRINGER SPEC SURG S PY 2009 BP 195 EP 211 DI 10.1007/978-1-84628-881-4_14 D2 10.1007/978-1-84628-881-4 PG 17 WC Endocrinology & Metabolism; Surgery SC Endocrinology & Metabolism; Surgery GA BKO03 UT WOS:000268741400014 ER PT S AU Kang, DK Suter, MJ Boudoux, C Yachimski, PS Bouma, BE Nishioka, NS Tearney, GJ AF Kang, DongKyun Suter, Melissa J. Boudoux, Caroline Yachimski, Patrick S. Bouma, Brett E. Nishioka, Norman S. Tearney, Guillermo J. BE Tearney, GJ Wang, TD TI Combined spectrally encoded confocal microscopy and optical frequency domain imaging system SO ENDOSCOPIC MICROSCOPY IV SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Endoscopic Microscopy IV CY JAN 25-26, 2009 CL San Jose, CA SP SPIE DE confocal microscopy; optical coherence tomography; Barrett's esophagus ID BARRETTS-ESOPHAGUS AB Spectrally encoded confocal microscopy (SECM) and optical frequency domain imaging (OFDI) are two reflectance-based imaging technologies that may be utilized for high-resolution microscopic screening of internal organs. SECM provides en face images of tissues with a high lateral resolution of 1-2 mu m, and a penetration depth of up to 300 mu m. OFDI generates cross-sectional images of tissue architecture with a resolution of 10-20 mu m and a penetration depth of 1-2 mm. Since the two technologies yield complementary microscopic information on two different size scales (SECMcellular and OFDI-architectural) that are commonly used for histopathologic evaluation, their combination may allow for more accurate optical diagnosis. Here, we report the integration of these two imaging modalities in a single bench top system. SECM images of swine small intestine showed the presence of goblet cells, and OFDI images revealed the finger-shaped villous architecture. In clinical study of 9 gastroesophageal biopsies from 8 patients, a diverse set of architectural and cellular features was observed, including squamous mucosa with mild hyperplasia and gastric antral mucosa with gastric pits and crypts. The capability of this multimodality device to enable the visualization of microscopic features on these two size scales supports our hypothesis that improved diagnostic accuracy may be obtained by merging these two technologies into a single instrument. C1 [Kang, DongKyun; Suter, Melissa J.; Boudoux, Caroline; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Kang, DK (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7418-6 J9 P SOC PHOTO-OPT INS PY 2009 VL 7172 AR 717206 DI 10.1117/12.808028 PG 7 WC Gastroenterology & Hepatology; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BSL22 UT WOS:000284823200003 ER PT B AU Yachimski, P Hur, C AF Yachimski, Patrick Hur, Chin BE Sampliner, RE TI Cost-Effectiveness of Endoscopic Therapy for Barrett's Esophagus SO ENDOSCOPIC THERAPY FOR BARRETT'S ESOPHAGUS SE Clinical Gastroenterology LA English DT Article; Book Chapter DE Barrett's esophagus; Cost-effectiveness; Photodynamic therapy; Esophagectomy ID HIGH-GRADE DYSPLASIA; PHOTODYNAMIC THERAPY; FOLLOW-UP; SURVEILLANCE; HEALTH; ADENOCARCINOMA; PATHOLOGISTS; PREFERENCES; MANAGEMENT; DISEASE AB Management options for Barrett's esophagus with high-grade dysplasia include intensive endoscopic Surveillance, surgrical esophagectomy, or endoscopic ablation therapy. Controlled, prospective trials comparing these treatment strategies have not been performed. In addition, clinical uncertainty may exist with respect to the accuracy of diagnosis of Barrett's high-grade dysplasia, risk of cancer progression, and likelihood of durable treatment outcome. Disease models can simulate risk over time in an attempt to account for these uncertainties. Cost-effectiveness analyses, based on these models, can be used to compare the relative costs and outcomes of endoscopic therapy for Barrett's esophagus with high-grade dysplasia, compared to surgery or surveillance strategies. C1 [Yachimski, Patrick; Hur, Chin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Hur, Chin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. RP Yachimski, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. OI Hur, Chin/0000-0002-2819-7576 NR 31 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-444-9 J9 CLIN GASTROENT-SER PY 2009 BP 165 EP 185 DI 10.1007/978-1-60327-445-6_10 D2 10.1007/978-1-60327-445-6 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BKX46 UT WOS:000269527800010 ER PT J AU Bronstein, J Carvey, P Chen, H Cory-Slechta, D DiMonte, D Duda, J English, P Goldman, S Grate, S Hansen, J Hoppin, J Jewell, S Kamel, F Koroshetz, W Langston, JW Logroscino, G Nelson, L Ravina, B Rocca, W Ross, GW Schettler, T Schwarzschild, M Scott, B Seegal, R Singleton, A Steenland, K Tanner, CM Van Den Eeden, S Weisskopf, M AF Bronstein, Jeff Carvey, Paul Chen, Honglei Cory-Slechta, Deborah DiMonte, Donato Duda, John English, Paul Goldman, Samuel Grate, Stephen Hansen, Johnni Hoppin, Jane Jewell, Sarah Kamel, Freya Koroshetz, Walter Langston, James W. Logroscino, Giancarlo Nelson, Lorene Ravina, Bernard Rocca, Walter Ross, George W. Schettler, Ted Schwarzschild, Michael Scott, Bill Seegal, Richard Singleton, Andrew Steenland, Kyle Tanner, Caroline M. Van Den Eeden, Stephen Weisskopf, Marc TI Meeting Report: Consensus Statement-Parkinson's Disease and the Environment: Collaborative on Health and the Environment and Parkinson's Action Network (CHE PAN) Conference 26-28 June 2007 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cholesterol; coffee; dairy products; diet; dopamine; fatty acids; metals; nonsteroidal anti-inflammatory drugs; Parkinson's disease; pesticides; polychlorinated biphenyls; smoking; statins; urate ID BODY-MASS INDEX; ALPHA-SYNUCLEIN; RISK-FACTORS; LEWY BODIES; PESTICIDE EXPOSURE; SUBSTANTIA-NIGRA; VITAMIN-C; COFFEE; MEN; METAANALYSIS AB BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. METHODS: In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. RESULTS: We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. CONCLUSIONS: PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders. C1 [DiMonte, Donato; Goldman, Samuel; Jewell, Sarah; Langston, James W.; Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA 94085 USA. [DiMonte, Donato; Goldman, Samuel; Jewell, Sarah; Langston, James W.; Tanner, Caroline M.] Ctr Clin, Sunnyvale, CA USA. [Bronstein, Jeff] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Carvey, Paul] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Chen, Honglei; Hoppin, Jane; Kamel, Freya] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Cory-Slechta, Deborah] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Duda, John] Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [English, Paul] Calif Dept Hlth Serv, Oakland, CA USA. [Grate, Stephen] USA, Med Res & Mat Command, Ft Detrick, MD USA. [Hansen, Johnni] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Koroshetz, Walter] NINDS, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Logroscino, Giancarlo] Univ Bari, Bari, Italy. [Nelson, Lorene] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Ravina, Bernard] Univ Rochester, Sch Med, Rochester, NY USA. [Rocca, Walter] Mayo Clin, Rochester, MN USA. [Ross, George W.] Pacific Hlth Res Inst, Honolulu, HI USA. [Schettler, Ted] Sci & Environm Hlth Network, Ames, IA USA. [Schwarzschild, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Scott, Bill] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Seegal, Richard] New York State Dept Hlth, Albany, NY USA. [Singleton, Andrew] NIH, Bethesda, MD 20892 USA. [Steenland, Kyle] Rollins Sch Publ Hlth, Atlanta, GA USA. [Van Den Eeden, Stephen] Kaiser Permanente, Oakland, CA USA. [Weisskopf, Marc] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Tanner, CM (reprint author), Parkinsons Inst, 675 Almanor Ave, Sunnyvale, CA 94085 USA. EM ctanner@thepi.org RI Singleton, Andrew/C-3010-2009; Nelson, Lorene/D-1305-2011; LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Jewell, Sarah/0000-0002-9877-2599; Kamel, Freya/0000-0001-5052-6615; Chen, Honglei/0000-0003-3446-7779 NR 79 TC 32 Z9 33 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2009 VL 117 IS 1 BP 117 EP 121 DI 10.1289/ehp.11702 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 394WN UT WOS:000262483900039 PM 19165397 ER PT J AU Major, P Rakowski, S Simon, MV Cheng, ML Eskandar, E Baron, J Leeman, BA Frosch, MP Thiele, EA AF Major, Philippe Rakowski, Sonja Simon, Mirela V. Cheng, Ming L. Eskandar, Emad Baron, Joshua Leeman, Beth A. Frosch, Matthew P. Thiele, Elizabeth A. TI Are cortical tubers epileptogenic? Evidence from electrocorticography SO EPILEPSIA LA English DT Article DE Electrocorticography; Epilepsy surgery; Tuberous sclerosis complex; Epileptogenesis; Cortical tubers ID SCLEROSIS COMPLEX; PRESURGICAL EVALUATION; INTRAOPERATIVE ELECTROCORTICOGRAPHY; INTRINSIC EPILEPTOGENICITY; SUBDURAL ELECTRODES; EPILEPSY SURGERY; DYSPLASIA; CHILDREN; DEPTH; MAGNETOENCEPHALOGRAPHY AB The purpose of this study was to characterize the epileptogenicity of tubers and surrounding cortex in patients with tuberous sclerosis complex (TSC). Three pediatric patients with TSC and intractable epilepsy underwent surgical resection of tubers associated with epileptogenic foci. In all patients, presurgical imaging revealed a prominent tuber that correlated on electroencephalography (EEG) with frequent interictal epileptiform discharges and electrographic seizures. Intracranial electrocorticography (ECoG) was performed using subdural grids placed over the tuber and surrounding cortex and depth electrodes positioned directly within the tuber. In all three patients, the depth electrode within the tuber was electrographically silent, whereas the surrounding cortical tissue showed significant epileptiform activity. The tuber and the electrically active adjacent cortex were resected. The patients experienced a drastic reduction in seizure frequency postsurgery. Epileptogenicity of cortical tubers may derive not from the lesion itself, but rather from the perturbation or abnormal development of the surrounding cortex. C1 [Major, Philippe; Simon, Mirela V.; Baron, Joshua; Leeman, Beth A.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rakowski, Sonja; Cheng, Ming L.; Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Herscot Ctr, Tuberous Sclerosis Complex,175 Cambridge St,Suite, Boston, MA 02114 USA. EM ethiele@partners.org FU Carol and James Herscot Center for Tuberous Sclerosis Complex FX Disclosure of conflicts of interest: None of the authors has any conflict of interest to disclose. NR 24 TC 71 Z9 73 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2009 VL 50 IS 1 BP 147 EP 154 DI 10.1111/j.1528-1167.2008.01814.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 391HN UT WOS:000262224500015 PM 19125835 ER PT S AU Frieder, M Lewinsohn, DM AF Frieder, Marisa Lewinsohn, David M. BE Reineke, U Schutkowski, M TI T-Cell Epitope Mapping in Mycobacterium tuberculosis Using PepMixes Created by Micro-Scale SPOT (TM)- Synthesis SO EPITOPE MAPPING PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Tuberculosis; CD8+T cells; Immunodominance; Antigen/epitope discovery; Elispot; Peptide library ID INFECTION; IDENTIFICATION; RESISTANCE; ANTIGEN; MICE; LYMPHOCYTES; COMPLEX; MACROPHAGES; PROTECTION; DEFICIENT AB Mycobacterium tuberculosis (Mtb) remains a major threat to human health worldwide. Although treatment of infection is an important part of tuberculosis control, an improved vaccine is essential for the elimination of this disease. Control of infection with Mtb is dependent on the cellular immune system, which in turn requires an understanding of those antigens that are capable Of stimulating CD4+ and CD8+ T-cell responses. Peptide libraries provide a high-throughput system for identifying novel T-cell epitopes. They can also be used to assess the hierarchy of immunodominance of these novel antigens and epitopes that are associated with infection with Mtb. This T-cell-driven means of antigen discovery is well adapted to vaccine development as wen as developing the tools necessary to understand the natural history of this important human pathogen. C1 [Frieder, Marisa; Lewinsohn, David M.] Portland VA Med Ctr, Pulm & CCM, R&D 11, Portland, OR USA. RP Frieder, M (reprint author), Portland VA Med Ctr, Pulm & CCM, R&D 11, Portland, OR USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 28 TC 3 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-17-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 524 BP 369 EP 382 DI 10.1007/978-1-59745-450-6_27 D2 10.1007/978-1-59745-450-6 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKJ95 UT WOS:000268335800027 PM 19377959 ER PT B AU Lane, AM Gragoudas, ES AF Lane, Anne Marie Gragoudas, Evangelos S. BE Singh, AD Damato, BE Peer, J Murphree, AL Perry, JD TI Uveal Malignant Melanoma: Management Options-Proton Beam Radiotherapy SO ESSENTIALS OF OPHTHALMIC ONCOLOGY LA English DT Article; Book Chapter C1 [Lane, Anne Marie] Massachusetts Eye & Ear Infirm, Retina Res Unit, Boston, MA 02114 USA. [Gragoudas, Evangelos S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. RP Lane, AM (reprint author), Massachusetts Eye & Ear Infirm, Retina Res Unit, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-917-0 PY 2009 BP 102 EP 103 PG 2 WC Oncology; Ophthalmology SC Oncology; Ophthalmology GA BKQ87 UT WOS:000268968200043 ER PT J AU Cheng, T Scadden, DT AF Cheng, Tao Scadden, David T. BE Lanza, R Gearhart, J Hogan, B Melton, D Pedersen, R Thomas, ED Thomson, J Wilmut, I TI Cell Cycle Regulators in Adult Stem Cells SO ESSENTIALS OF STEM CELL BIOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID CDK INHIBITORS; SELF-RENEWAL; P21(CIP1/WAF1); PROGRESSION; QUIESCENCE; P27(KIP1) C1 [Cheng, Tao; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Cheng, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088497-4 PY 2009 BP 81 EP 87 DI 10.1016/B978-0-12-374729-7.00009-3 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA BCR48 UT WOS:000311099200014 ER PT J AU Bonner-Weir, S Weir, GC AF Bonner-Weir, Susan Weir, Gordon C. BE Lanza, R Gearhart, J Hogan, B Melton, D Pedersen, R Thomas, ED Thomson, J Wilmut, I TI Insulin-producing Cells Derived from Stem Cells: A Potential Treatment for Diabetes SO ESSENTIALS OF STEM CELL BIOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID BETA-CELLS; IN-VIVO; PANCREAS; ISLETS C1 [Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. OI Bonner-Weir, Susan/0000-0003-4682-0656 NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088497-4 PY 2009 BP 513 EP 521 DI 10.1016/B978-0-12-374729-7.00057-3 PG 9 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA BCR48 UT WOS:000311099200062 ER PT J AU De Jesus, M AF De Jesus, Maria TI Mutuality at the center: health promotion with Cape Verdean immigrant women SO ETHNICITY & HEALTH LA English DT Article DE Cape Verdean immigrant women; mutuality; health promotion ID ILLNESS RESOURCES SURVEY; COMMUNITY-HEALTH; SOCIAL-CONTEXT; WORKING-CLASS; WORKERS; ISSUES AB Objective. Public health care researchers, policy makers, and providers are increasingly interested in developing more effective and culturally responsive health promotion theories and interventions for diverse immigrant populations. The purpose of this study was to develop health promotion theory that validates the local knowledge and experiences of Cape Verdean women health promoters who work with immigrant women in their community. Design. In-depth, semi-structured interviews were conducted with nine culturally savvy, community-based Cape Verdean women health promoters about their perspectives and daily experiences of health promotion practice with Cape Verdean immigrant women. This study used Glaserian grounded theory to analyze the interviews. This approach identified concepts and developed an integrated process through which to theorize about the practice of health promoters. Results. For Cape Verdean women health promoters, a process of creating relationships was a key to promoting women's health. The relational theory of health promotion practice reflects these dynamic processes, properties, and stages through which Cape Verdean women health promoters develop mutually engaging relationships with immigrant women. Conclusion. These findings challenge health care professionals to broaden the repertoire of health promotion strategies to include relationship-building between health promoters and community women. Through these relationships health promoters can understand the complex structural, cultural, and community factors that influence immigrant women's health and incorporate that knowledge into more effective health promotion practices. C1 [De Jesus, Maria] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [De Jesus, Maria] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP De Jesus, M (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM maria_dejesus@dfci.harvard.edu NR 33 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-7858 J9 ETHNIC HEALTH JI Ethn. Health PY 2009 VL 14 IS 1 BP 45 EP 59 AR PII 907867607 DI 10.1080/13557850802023141 PG 15 WC Ethnic Studies; Public, Environmental & Occupational Health SC Ethnic Studies; Public, Environmental & Occupational Health GA 395LH UT WOS:000262525100004 PM 19152158 ER PT J AU Daemen, J Simoons, ML Wijns, W Bagust, A Bos, G Bowen, JM Braunwald, E Camenzind, E Chevalier, B DiMario, C Fajadet, J Gitt, A Guagliumi, G Hillege, HL James, S Juni, P Kastrati, A Kloth, S Kristensen, SD Krucoff, M Legrand, V Pfisterer, M Rothman, M Serruys, PW Silber, S Steg, PG Tariah, I Wallentin, L Windecker, SW AF Daemen, Joost Simoons, Maarten L. Wijns, William Bagust, Adrian Bos, Gert Bowen, James M. Braunwald, Eugene Camenzind, Edoardo Chevalier, Bernard DiMario, Carlo Fajadet, Jean Gitt, Anselm Guagliumi, Giulio Hillege, Hans L. James, Stefan Jueni, Peter Kastrati, Adnan Kloth, Sabine Kristensen, Steen D. Krucoff, Mitchell Legrand, Victor Pfisterer, Matthias Rothman, Martin Serruys, Patrick W. Silber, Sigmund Steg, Philippe G. Tariah, Ibrahim Wallentin, Lars Windecker, Stephan W. TI Meeting report ESC Forum on Drug Eluting Stents, European Heart House, Nice, 27-28 September 2007 SO EUROINTERVENTION LA English DT Article ID BARE-METAL STENTS; CORONARY-ARTERY LESIONS; MYOCARDIAL-INFARCTION; CLINICAL-OUTCOMES; STANDARD STENT; SLOW-RELEASE; DOUBLE-BLIND; FOLLOW-UP; THROMBOSIS; TRIAL C1 [Daemen, Joost; Simoons, Maarten L.; Serruys, Patrick W.] Erasmus MC, Thoraxctr, Rotterdam, Netherlands. [Wijns, William] Onze Lieve Vrouw Hosp, Ctr Cardiovasc, Aalst, Belgium. [Bagust, Adrian] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Bos, Gert] KEMA Med, Arnhem, Netherlands. [Bos, Gert] KEMA Med, Munich, Germany. [Bos, Gert] KEMA Med, Tel Aviv, Israel. [Bos, Gert] KEMA Med, Chalfont, PA USA. [Bos, Gert] KEMA Med, Lafayette, CA USA. [Bos, Gert] KEMA Med, Tokyo, Japan. [Bowen, James M.] St Josephs Healthcare Hamilton McMaster Univ, Programs Assessment Technol Hlth PATH Res Inst, Hamilton, ON, Canada. [Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. [Camenzind, Edoardo] Univ Geneva, Geneva, Switzerland. [Chevalier, Bernard] Inst Cardiovasc Paris Sud, Massy, France. [DiMario, Carlo] Univ London Imperial Coll Sci Technol & Med, NHLI, London, England. [Fajadet, Jean] Clin Pasteur, Toulouse, France. [Gitt, Anselm] Univ Heidelberg, Ludwigshafen, Germany. [Guagliumi, Giulio] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Trial Coordinat Ctr, Groningen, Netherlands. [James, Stefan; Wallentin, Lars] Univ Uppsala Hosp, Uppsala Clin Res Ctr, Dept Med Sci & Cardiol, Uppsala, Sweden. [Jueni, Peter] Univ Bern, Dept Social & Prevent Med, Div Clin Epidemiol & Biostat, Bern, Switzerland. [Kastrati, Adnan] Deutsch Herzzentrum Munich, Munich, Germany. [Kloth, Sabine] TUV SUD Prod Serv GmbH, Munich, Germany. [Kristensen, Steen D.] Aarhus Univ Hosp, Dept Cardiol, Skejby, Denmark. [Krucoff, Mitchell] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Legrand, Victor] CHU Sart Tilman, B-4000 Liege, Belgium. [Pfisterer, Matthias] Univ Basel Hosp, Dept Cardiol, CH-4031 Basel, Switzerland. [Rothman, Martin] London Chest Hosp, London E2 9JX, England. [Silber, Sigmund] Cardiol Practice & Hosp, Munich, Germany. [Steg, Philippe G.] Hop Bichat Claude Bernard, F-75877 Paris, France. [Windecker, Stephan W.] Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland. RP Daemen, J (reprint author), Erasmus MC, Thoraxctr, Rotterdam, Netherlands. OI Campo, Gianluca/0000-0002-5150-188X NR 45 TC 4 Z9 5 U1 0 U2 0 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD JAN PY 2009 VL 4 IS 4 BP 427 EP 436 DI 10.4244/EIJV4I4A75 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V18YW UT WOS:000208041100005 PM 19284063 ER PT J AU Sabatine, MS Morrow, DA de Lemos, JA Jarolim, P Braunwald, E AF Sabatine, Marc S. Morrow, David A. de Lemos, James A. Jarolim, Petr Braunwald, Eugene TI Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35 SO EUROPEAN HEART JOURNAL LA English DT Article ID CARDIAC TROPONIN; INTRACELLULAR COMPARTMENTATION; RELEASE KINETICS; INFARCTION; ELEVATION; INJURY; HEART AB To determine whether an ultrasensitive assay can permit quantification of changes in circulating cardiac troponin (Tn) in the setting of stress test-induced myocardial ischaemia. Blood samples were obtained before, immediately after, and 2 and 4 h after stress testing with nuclear perfusion imaging in 120 patients. Troponin was measured using commercial assays as well as with a novel, ultrasensitive cardiac TnI assay with a limit of detection of 0.2 pg/mL. Using the ultrasensitive assay, TnI was detectable in all patients before stress testing (median 4.4 pg/mL, interquartile range 3.1-8.6 pg/mL). By 4 h, troponin levels were unchanged in patients without ischaemia, whereas circulating levels had increased by a median of 1.4 pg/mL (24% increase) in patients with mild ischaemia (P = 0.002) and by 2.1 pg/mL (40% increase) in patients with moderate-to-severe ischaemia (P = 0.0006). In contrast, changes in troponin levels across patients in different ischaemic categories were indistinguishable using commercial troponin assays. When added to clinical factors, a > 1.3 pg/mL increase in TnI using the ultrasensitive assay was an independent predictor of ischaemia (odds ratio 3.54, P = 0.007). Transient stress test-induced myocardial ischaemia is associated with a quantifiable increase in circulating troponin that is detectable with a novel, ultrasensitive TnI assay. C1 [Sabatine, Marc S.; Morrow, David A.; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Sabatine, Marc S.; Morrow, David A.; Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sabatine, Marc S.] Brigham & Womens Hosp, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. [de Lemos, James A.] Univ Texas SW Med Ctr Dallas, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. [de Lemos, James A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Jarolim, Petr] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU NIH [U01 HL083-1341] FX Measurement of cardiac troponin I using the Singulex Erenna System was performed by Singulex, Inc. Measurement of B-type natriuretic peptide was performed by Biosite, Inc. M. S. S. and D. A. M. are supported in part by NIH grant U01 HL083-1341. M. S. S. and J.A.de.L. are supported in part by the Donald W. Reynolds Foundation. M. S. S. has received research grant support from Ortho-Clinical Diagnostics and Roche Diagnostics. D. A. M. has received honoraria for educational presentations from Bayer Diagnostics, Beckman-Coulter, Dade-Behring, Sanofi-Aventis, and Roche Diagnostics. He has served as a consultant for GlaxoSmithKline and Sanofi-Aventis and on advisory boards for Beckman-Coulter, Critical Diagnostics, Genentech, OrthoClinical Diagnostics, Roche Diagnositcs, and Siemens Medical Solutions. J. A. de. L. has received research grant support and/or honoraria from Biosite and Roche. P. J. has received honoraria from Siemens. E. NR 28 TC 166 Z9 171 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2009 VL 30 IS 2 BP 162 EP 169 DI 10.1093/eurheartj/ehn504 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 395IY UT WOS:000262519000008 PM 18997177 ER PT J AU Cacoub, PP Bhatt, DL Steg, PG Topol, EJ Creager, MA AF Cacoub, Patrice P. Bhatt, Deepak L. Steg, P. Gabriel Topol, Eric J. Creager, Mark A. CA CHARISMA Investigators TI Patients with peripheral arterial disease in the CHARISMA trial SO EUROPEAN HEART JOURNAL LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; ISCHEMIC EVENTS; CLOPIDOGREL; ASPIRIN; RISK; PREVENTION; MANAGEMENT; ATHEROTHROMBOSIS AB The aim of this study was to determine whether clopidogrel plus aspirin provides greater protection against major cardiovascular events than aspirin alone in patients with peripheral arterial disease (PAD). This is a post hoc analysis of the 3096 patients with symptomatic (2838) or asymptomatic (258) PAD from the CHARISMA trial. The rate of cardiovascular death, myocardial infarction (MI), or stroke (primary endpoint) was higher in patients with PAD than in those without PAD: 8.2% vs. 6.8% [hazard ratio (HR), 1.25; 95% CI 1.08, 1.44; P = 0.002]. Among the patients with PAD, the primary endpoint occurred in 7.6% in the clopidogrel plus aspirin group and 8.9% in the placebo plus aspirin group (HR, 0.85; 95% CI, 0.66-1.08; P = 0.18). In these patients, the rate of MI was lower in the dual antiplatelet arm than the aspirin alone arm: 2.3% vs. 3.7% (HR, 0.63; 95% CI, 0.42-0.96; P = 0.029), as was the rate of hospitalization for ischaemic events: 16.5% vs. 20.1% (HR, 0.81; 95% CI, 0.68-0.95; P = 0.011). The rates of severe, fatal, or moderate bleeding did not differ between the groups, whereas minor bleeding was increased with clopidogrel: 34.4% vs. 20.8% (odds ratio, 1.99; 95% CI, 1.69-2.34; P < 0.001). Dual therapy provided some benefit over aspirin alone in PAD patients for the rate of MI and the rate of hospitalization for ischaemic events, at the cost of an increase in minor bleeding. C1 [Cacoub, Patrice P.] La Pitie Salpetriere Hosp, Dept Internal Med, AP HP, F-75651 Paris 13, France. [Cacoub, Patrice P.] Univ Paris 06, CNRS, UMR 7087, Paris, France. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02115 USA. [Steg, P. Gabriel] Univ Paris 07, Bichat Hosp, Dept Cardiol, AP HP, Paris, France. [Steg, P. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Topol, Eric J.] Scripps Clin, Scripps Translat Sci Inst, La Jolla, CA 92037 USA. [Topol, Eric J.] Scripps Hlth, La Jolla, CA 92037 USA. [Creager, Mark A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Creager, Mark A.] Harvard Univ, Sch Med, Boston, MA USA. RP Cacoub, PP (reprint author), La Pitie Salpetriere Hosp, Dept Internal Med, AP HP, 47-83 Blvd Hop, F-75651 Paris 13, France. EM patrice.cacoub@psl.aphp.fr RI Walker, Philip/F-3034-2010; OI Topol, Eric/0000-0002-1478-4729 FU Sanofi-Aventis; Bristol-Myers Squibb FX The CHARISMA trial was funded by Sanofi-Aventis and Bristol-Myers Squibb. NR 23 TC 97 Z9 100 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2009 VL 30 IS 2 BP 192 EP 201 DI 10.1093/eurheartj/ehn534 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 395IY UT WOS:000262519000013 PM 19136484 ER PT J AU DeMarinis, V Barsky, AJ Antin, JH Chang, G AF DeMarinis, V. Barsky, A. J. Antin, J. H. Chang, G. TI Health psychology and distress after haematopoietic stem cell transplantation SO EUROPEAN JOURNAL OF CANCER CARE LA English DT Article DE health psychology; cancer; depression; adults; quality of life; stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; QUALITY-OF-LIFE; CHRONIC MYELOID-LEUKEMIA; III-R HYPOCHONDRIASIS; LONG-TERM SURVIVORS; CANCER SURVIVORS; ADULT SURVIVORS; DEPRESSION; WORK; SATISFACTION AB The purpose of this study of 23 adult haematopoietic stem cell transplantation (HSCT) recipients is to compare the presence of post-transplantation depression disorders by gender and to compare the outcomes among those with and without depressive disorders using a health psychology focus. This cross-sectional pilot study of mid-term survivors took place in hospital outpatient clinic. Main outcome measures are depression disorders, health status (Short Form-12) and health anxiety. Female survivors had a higher rate of depression disorders, but those with treated depressive disorders were similar to those without depression on health-related quality of life and health anxiety. Neither patient age nor time since HSCT was associated with depressive disorders. A health psychology approach may enhance management of HSCT survivorship. C1 [Barsky, A. J.; Chang, G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Barsky, A. J.; Chang, G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [DeMarinis, V.] Dept Psychiat, Medford, MA USA. [DeMarinis, V.] Uppsala Univ, Dept Psychol, Uppsala, Sweden. [Antin, J. H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Antin, J. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Chang, G (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. EM gchang@partners.org OI DeMarinis, Valerie/0000-0002-1248-9988 FU National Institute on Alcohol Abuse and Alcoholism [K24 AA 00289] FX Source of funding: This study was funded in part by K24 AA 00289 (GC) from the National Institute on Alcohol Abuse and Alcoholism. NR 47 TC 7 Z9 7 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0961-5423 J9 EUR J CANCER CARE JI Eur. J. Cancer Care PD JAN PY 2009 VL 18 IS 1 BP 57 EP 63 DI 10.1111/j.1365-2354.2008.00931.x PG 7 WC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation SC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation GA 392DJ UT WOS:000262282800011 PM 19473223 ER PT J AU Baumgartner, H Hung, J Bermejo, J Chambers, JB Evangelista, A Griffin, BP Iung, B Otto, CM Pellikka, PA Quinones, M AF Baumgartner, Helmut Hung, Judy Bermejo, Javier Chambers, John B. Evangelista, Arturo Griffin, Brian P. Iung, Bernard Otto, Catherine M. Pellikka, Patricia A. Quinones, Miguel TI Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice SO EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY LA English DT Review ID PRESSURE HALF-TIME; PERCUTANEOUS MITRAL COMMISSUROTOMY; VALVULAR AORTIC-STENOSIS; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; PULMONARY-ARTERY PRESSURE; RHEUMATIC HEART-DISEASE; DOPPLER-ECHOCARDIOGRAPHY; TRICUSPID STENOSIS; RISK STRATIFICATION; NONINVASIVE ASSESSMENT C1 [Baumgartner, Helmut] Univ Munster, Munster, Germany. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bermejo, Javier] Hosp Gen Univ Gregorio Maranon, Barcelona, Spain. [Chambers, John B.] Huys & St Thomas Hosp, London, England. [Evangelista, Arturo] Hosp Gen Valle Hebron, Barcelona, Spain. [Griffin, Brian P.] Cleveland Clin, Cleveland, OH 44106 USA. [Iung, Bernard] Univ Paris 07, Paris, France. [Otto, Catherine M.] Univ Washington, Seattle, WA 98195 USA. [Pellikka, Patricia A.] Mayo Clin, Rochester, MN USA. [Quinones, Miguel] Methodist Hosp, Houston, TX 77030 USA. RP Baumgartner, H (reprint author), Univ Munster, Munster, Germany. OI Otto, Catherine/0000-0002-0527-9392 NR 109 TC 206 Z9 210 U1 4 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1525-2167 J9 EUR J ECHOCARDIOGR JI Eur. J. Echocardiogr. PD JAN PY 2009 VL 10 IS 1 BP 1 EP 25 DI 10.1093/ejechocard/jen303 PG 25 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 392VF UT WOS:000262329600001 PM 19065003 ER PT J AU Senior, R Monaghan, M Main, ML Zamorano, JL Tiemann, K Agati, L Weissman, NJ Klein, AL Marwick, TH Ahmad, M DeMaria, AN Zabalgoitia, M Becher, H Kaul, S Udelson, JE Wackers, FJ Walovitch, RC Picard, MH AF Senior, Roxy Monaghan, Mark Main, Michael L. Zamorano, Jose L. Tiemann, Klaus Agati, Luciano Weissman, Neil J. Klein, Allan L. Marwick, Thomas H. Ahmad, Masood DeMaria, Anthony N. Zabalgoitia, Miguel Becher, Harald Kaul, Sanjiv Udelson, James E. Wackers, Frans J. Walovitch, Richard C. Picard, Michael H. CA Ramp-1 & Ramp-2 Investigators TI Detection of coronary artery disease with perfusion stress echocardiography using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radionuclide perfusion imaging SO EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY LA English DT Article ID MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; EMISSION COMPUTED-TOMOGRAPHY; DIPYRIDAMOLE STRESS; ADENOSINE; STENOSIS; QUANTIFICATION; DOBUTAMINE; VALIDATION; DIAGNOSIS; RESERVE AB To determine if perfusion stress echocardiography (PSE) with Imagify (TM) (perflubutane polymer microspheres) is comparable to stress perfusion imaging using Tc-99m single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD. Chronic, stable, chest pain patients (n = 662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha = 0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66-71%, P <= 0.004). Four demonstrated non-inferior sensitivity (68-77%, P <= 0.002), three demonstrated non-inferior specificity (72-88%, P <= 0.013). Three PSE readers (RAMP-2) were superior for sensitivity. Two PSE readers (RAMP-1) were superior for specificity. Area under the multi-reader receiver operating characteristics curve (0.72) was equal for both modalities. Majority of adverse events followed dipyridamole dosing, and were mild, transient, and required no treatment. Imagify PSE was well-tolerated. Its diagnostic performance in chest pain patients is comparable with SPECT perfusion imaging. C1 [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Dept Cardiovasc Med, Harrow HA1 3UJ, Middx, England. [Monaghan, Mark] Kings Coll Hosp London, London SE5 9RS, England. [Main, Michael L.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Zamorano, Jose L.] Univ Clin San Carlos, Serv Ecocardiol, Madrid 28040, Spain. [Tiemann, Klaus] Univ Bonn, Dept Cardiol, D-53105 Bonn, Germany. [Agati, Luciano] Univ Roma La Sapienza, Dept Cardiol, I-00161 Rome, Italy. [Weissman, Neil J.] Cardiovasc Res Inst, Washington, DC 20010 USA. [Klein, Allan L.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Marwick, Thomas H.] Univ Queensland, Sch Med, Princess Alexandra Hosp, Woolloongabba, Qld 4102, Australia. [Ahmad, Masood] Univ Texas Galveston, Div Cardiol, Galveston, TX 77555 USA. [DeMaria, Anthony N.] UCSD Med Ctr, Div Cardiol, San Diego, CA 92103 USA. [Zabalgoitia, Miguel] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Becher, Harald] John Radcliffe Hosp, Oxford OX3 9DZ, England. [Kaul, Sanjiv] OHSU, Portland, OR 97239 USA. [Udelson, James E.] Tufts Univ New England Med Ctr, Div Cardiol, Dept Med, Boston, MA 02111 USA. [Wackers, Frans J.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Walovitch, Richard C.] Acusphere Inc, Watertown, MA 02472 USA. [Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Senior, R (reprint author), Middlesex Univ, London N17 8HR, England. EM roxysenior@cardiac-research.org RI Marwick, Thomas/C-7261-2013; OI Marwick, Thomas/0000-0001-9065-0899; agati, luciano/0000-0003-3186-1797; Picard, Michael/0000-0002-9264-3243 FU Acusphere, Inc [NCT00156793, NCT00156845] FX The authors acknowledge Asli Memisoglu and Mrudula Donepudi (Acusphere, Inc.) for statistical analyses of clinical trial data and for assistance in manuscript preparation, respectively. The authors acknowledge all study investigators who participated in both RAMP-1 and RAMP-2 clinical trials including: Drs Kwan Chan, Judy Finney, Linda Gillam, Michael Imburgia, James Jollis, Helmut Kuecherer, Stephane Lafitte, Wolfgang Lepper, Dominic Leung, Nelson Schiller, Douglas Segar, Jamshid Shirani, Mani Vannan, Jean Louis Vanoverschelde, Flordeliza Villanueva, Eric Yu. The authors acknowledge all blinded readers including: Drs Sharon Mulvagh, Thomas Porter, Kevin Wei, and Feng Xie for PSE images; Drs Marcelo Di Carli and Raymond Taillefer for SPECT images; Dr Ami Iskandrian (CAD reviewer); and Central Core Laboratory, Cardiovascular Research Foundation for cardiac angiography studies.; Conflict of interest: All authors except R. C. W. received consulting fees from Acusphere, Inc. or fees for clinical trial patient enrollment. RAMP-1 and -2 clinical trials were funded by Acusphere, Inc. R. C. W. is an employee and shareholder of Acusphere, Inc. ClinicalTrials. gov: NCT00156793, RAMP-1; NCT00156845, RAMP-2 NR 39 TC 40 Z9 42 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1525-2167 J9 EUR J ECHOCARDIOGR JI Eur. J. Echocardiogr. PD JAN PY 2009 VL 10 IS 1 BP 26 EP 35 DI 10.1093/ejechocard/jen321 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 392VF UT WOS:000262329600002 PM 19131498 ER PT J AU Neilan, TG Pradhan, AD King, ME Weyman, AE AF Neilan, Tomas G. Pradhan, Aruna D. King, Mary Etta Weyman, Arthur E. TI Derivation of a size-independent variable for scaling of cardiac dimensions in a normal paediatric population SO EUROPEAN JOURNAL OF ECHOCARDIOGRAPHY LA English DT Article ID LEFT-VENTRICULAR MASS; BODY-SURFACE AREA; CHILDREN; GROWTH; ADULTS; ADOLESCENTS; INFANTS; FORMULA; WEIGHT; HEIGHT AB It is general practice to correct cardiac chamber size for body size by the process of scaling or normalization. Normalization is most commonly performed using simple linear or isometric correction; however, there is increasing evidence that this approach may be flawed. Likewise, there is little agreement concerning the appropriate scaling variable (measure of body size) for normalization. Therefore, we aimed to establish the optimal method for correcting the differences in body size in a large population of echocardiographically normal paediatric subjects. We compared the relative ability of standard size variables including height (HT), body weight (BW), body mass index (BMI), and body surface area (BSA), in both isometric and allometric models, to remove the effect of body size in 4109 consecutive echocardiographically normal subjects < 18 years of age, using the left atrial dimension (LAD) as a reference standard. Simple linear normalization resulted in significant residual correlations (r = -0.57 to -0.92) of the indexed value with the body size variable, the correlations with weight (WT) and BSA actually increasing. In contrast, correction by the optimal allometric exponent (AE) removed the effects of the indexed variable (residual correlations -0.01 to 0.01), with BW and BSA best removing the effects of all the measures of body size. Conventional linear correction for body size is inaccurate in children and paradoxically increases the relationship of the indexed parameter with WT and BSA. Conversely, correction using the optimal AE removes the effect of that variable, with WT best correction for all measures of body size. C1 [Neilan, Tomas G.; King, Mary Etta; Weyman, Arthur E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Ultrasound Lab,Cardiol Div, Boston, MA 02115 USA. [Neilan, Tomas G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div,Cardiovasc Res Ctr, Boston, MA 02115 USA. [Pradhan, Aruna D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02115 USA. RP Weyman, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Ultrasound Lab,Cardiol Div, 55 Fruit St,YAW-5E, Boston, MA 02115 USA. EM aeweyman@partners.org FU American Heart Association; National Heart, Lung, and Blood Institute [HL 082740] FX This study was supported by grants from the American Heart Association (TGN, Post-Doctoral Fellowship Grant) and the National Heart, Lung, and Blood Institute (ADP, HL 082740). NR 21 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1525-2167 J9 EUR J ECHOCARDIOGR JI Eur. J. Echocardiogr. PD JAN PY 2009 VL 10 IS 1 BP 50 EP 55 DI 10.1093/ejechocard/jen110 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 392VF UT WOS:000262329600007 PM 18490317 ER PT J AU Little, J Higgins, JPT Ioannidis, JPA Moher, D Gagnon, F von Elm, E Khoury, M Cohen, B Davey-Smith, G Grimshaw, J Scheet, P Gwinn, M Williamson, RE Zou, GY Hutchings, K Johnson, CY Tait, V Wiens, M Golding, J van Duijn, C McLaughlin, J Paterson, A Wells, G Fortier, I Freedman, M Zecevic, M King, R Infante-Rivard, C Stewart, AFR Birkett, N AF Little, Julian Higgins, Julian P. T. Ioannidis, John P. A. Moher, David Gagnon, France von Elm, Erik Khoury, Muin J. Cohen, Barbara Davey-Smith, George Grimshaw, Jeremy Scheet, Paul Gwinn, Marta Williamson, Robin E. Zou, Guang Yong Hutchings, Kim Johnson, Candice Y. Tait, Valerie Wiens, Miriam Golding, Jean van Duijn, Cornelia McLaughlin, John Paterson, Andrew Wells, George Fortier, Isabel Freedman, Matthew Zecevic, Maja King, Richard Infante-Rivard, Claire Stewart, Alex F. R. Birkett, Nick TI Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE Gene-disease associations; Genetics; Gene-environment interaction; Systematic review; Meta analysis; Reporting recommendations; Epidemiology; Genome-wide association ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; POPULATION STRATIFICATION; RANDOMIZED-TRIALS; DISEASE ASSOCIATIONS; GENOTYPING ERRORS; COMPLEX DISEASES; PROSTATE-CANCER; LINKAGE-DISEQUILIBRIUM AB Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. C1 [Little, Julian; Moher, David; Hutchings, Kim; Johnson, Candice Y.; Tait, Valerie; Wiens, Miriam; Birkett, Nick] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada. [Little, Julian] Canada Res Chair Human Genome Epidemiol, Toronto, ON, Canada. [Higgins, Julian P. T.] MRC, Biostat Unit, Cambridge CB2 2BW, England. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA. [Gagnon, France] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada. [von Elm, Erik] Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland. [von Elm, Erik] Univ Med Ctr, Dept Med Biometry & Med Informat, German Cochrane Ctr, Freiburg, Germany. [Khoury, Muin J.; Gwinn, Marta] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA. [Cohen, Barbara] Publ Lib Sci, San Francisco, CA USA. [Davey-Smith, George] Univ Bristol, Dept Social Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Grimshaw, Jeremy] Univ Ottawa, Dept Med, Ottawa Hlth Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Scheet, Paul] Univ Texas Houston, Dept Epidemiol, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zou, Guang Yong] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Zou, Guang Yong] Robarts Res Inst, London, ON N6A 5C1, Canada. [van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Paterson, Andrew] Hosp Sick Children SickKids, Toronto, ON, Canada. [Wells, George] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. [Fortier, Isabel] McGill Univ, Genome Quebec & P3G Observ, Montreal, PQ H3A 1A4, Canada. [Fortier, Isabel] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. [Freedman, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Infante-Rivard, Claire] McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [Stewart, Alex F. R.] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada. RP Little, J (reprint author), Univ Ottawa, Dept Epidemiol & Community Med, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. EM jlittle@uottawa.ca RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Stewart, Alexandre/A-5677-2011; Grimshaw, Jeremy/D-8726-2013; McLaughlin, John/E-4577-2013; Paterson, Andrew/A-4088-2011; Davey Smith, George/A-7407-2013; OI Grimshaw, Jeremy/0000-0001-8015-8243; Golding, Jean/0000-0003-2826-3307; Higgins, Julian/0000-0002-8323-2514; Paterson, Andrew/0000-0002-9169-118X; Davey Smith, George/0000-0002-1407-8314; von Elm, Erik/0000-0002-7412-0406; Stewart, Alexandre/0000-0003-2673-9164; Moher , David /0000-0003-2434-4206 FU Medical Research Council [MC_U105285807] NR 154 TC 25 Z9 35 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD JAN PY 2009 VL 24 IS 1 BP 37 EP 55 DI 10.1007/s10654-008-9302-y PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 407KM UT WOS:000263362000006 PM 19189221 ER PT J AU Leleu, X Gay, J Roccaro, AM Moreau, AS Poulain, S Dulery, R Champs, BBD Robu, D Ghobrial, IM AF Leleu, Xavier Gay, Julie Roccaro, Aldo M. Moreau, Anne-Sophie Poulain, Stephanie Dulery, Remy Champs, Berenice Bro Des Robu, Daniela Ghobrial, Irene M. TI Update on therapeutic options in Waldenstrom macroglobulinemia SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Review DE Waldenstrom macroglobulinemia; novel therapy ID CONSENSUS PANEL RECOMMENDATIONS; REFRACTORY MULTIPLE-MYELOMA; 2ND INTERNATIONAL WORKSHOP; COOPERATIVE-ONCOLOGY-GROUP; IGM MONOCLONAL GAMMOPATHY; STEM-CELL TRANSPLANTATION; SINGLE-AGENT THALIDOMIDE; NON-HODGKIN-LYMPHOMA; OF-THE-LITERATURE; PROGNOSTIC-FACTORS AB Waldenstrom macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells (LPCs), along with demonstration of an IgM monoclonal gammopathy in the blood. WM remains incurable, with 5-6 yr median overall survival for patients with symptomatic WM. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either in monotherapy or in combination. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival are short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to develop new targeted therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors, of them bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Many agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. C1 [Leleu, Xavier; Gay, Julie; Moreau, Anne-Sophie; Dulery, Remy; Champs, Berenice Bro Des; Robu, Daniela] CHRU, Hop Huriez, Serv Malad Sang, Lille, France. [Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Kirsch Lab Waldenstrom Macroglobulinemia, Boston, MA 02115 USA. [Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA. [Roccaro, Aldo M.] Univ Brescia, Sch Med, Unit Blood Dis, Brescia, Italy. [Roccaro, Aldo M.] Univ Brescia, Sch Med, Unit Cell Therapies, Brescia, Italy. [Poulain, Stephanie] CHR, Ctr Hosp, Serv Hematol, Valenciennes, France. RP Leleu, X (reprint author), CHRU, Hop Huriez, Serv Malad Sang, Lille, France. EM x-leleu@chru-lille.fr OI Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [R21 CA126119, R21 CA126119-01A1] NR 97 TC 8 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-4441 EI 1600-0609 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JAN PY 2009 VL 82 IS 1 BP 1 EP 12 DI 10.1111/j.1600-0609.2008.01171.x PG 12 WC Hematology SC Hematology GA 383OX UT WOS:000261684000001 PM 19087134 ER PT J AU Fagerness, JA Maller, JB Neale, BM Reynolds, RC Daly, MJ Seddon, JM AF Fagerness, Jesen A. Maller, Julian B. Neale, Benjamin M. Reynolds, Robyn C. Daly, Mark J. Seddon, Johanna M. TI Variation near complement factor I is associated with risk of advanced AMD SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE AMD; macular degeneration; genetic association; complement pathway ID GENOME-WIDE ASSOCIATION; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; GENE; HAPLOTYPE; DISEASE; VARIANT; SYSTEM; CELLS; SCANS AB A case-control association study for advanced age-related macular degeneration was conducted to explore several regions of interest identified by linkage. This analysis identified a single nucleotide polymorphism just 3' of complement factor I on chromosome 4 showing significant association (P < 10(-7)). Sequencing was performed on coding exons in linkage disequilibrium with the detected association. No obvious functional variation was discovered that could be the proximate cause of the association, suggesting a noncoding regulatory mechanism. C1 [Reynolds, Robyn C.; Seddon, Johanna M.] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA. [Fagerness, Jesen A.; Maller, Julian B.; Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Fagerness, Jesen A.; Maller, Julian B.; Neale, Benjamin M.; Daly, Mark J.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Fagerness, Jesen A.; Maller, Julian B.; Neale, Benjamin M.; Daly, Mark J.] MIT, Cambridge, MA 02139 USA. [Maller, Julian B.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Neale, Benjamin M.] Kings Coll London, Inst Psychiat, SGDP Ctr, London, England. RP Seddon, JM (reprint author), Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, 800 Washington St,450, Boston, MA 02111 USA. EM jseddon@tuftsmedicalcenter.org OI Maller, Julian/0000-0002-1565-9559 FU National Institutes of Health [EY11309]; Foundation Fighting Blindness; Massachusetts Lions Research Fund; Research to Prevent Blindness; Macular Degeneration Research Fund; Ophthalmic Epidemiology and Genetics Service; New England Eye Center; Tufts Medical Center; enter for Inherited Disease Research; Broad Institute Center for Genotyping and Analysis [U54 RR020278]; National Center for Research Resources FX Funding was provided by the National Institutes of Health grant EY11309; the Foundation Fighting Blindness; the Massachusetts Lions Research Fund; Research to Prevent Blindness; Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, the New England Eye Center, Tufts Medical Center; Center for Inherited Disease Research; and the Broad Institute Center for Genotyping and Analysis (through grant U54 RR020278 from the National Center for Research Resources). We thank AREDS participants and investigators and the EMMES Corporation for their work on the AREDS Genetic Repository. We also thank Daniel Mirel, Brian Galloway (project management); Robb Onofrio, Rob Borowski, Kat Irzene, Tony Rachupka (genotyping/sequencing), David Turner, Meg Parker (sample management); and Chris Cotsapas (bioinformatics). NR 27 TC 180 Z9 185 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2009 VL 17 IS 1 BP 100 EP 104 DI 10.1038/ejhg.2008.140 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 382EU UT WOS:000261588800014 PM 18685559 ER PT J AU Medoff, BD Sandall, BP Landry, A Nagahama, K Mizoguchi, A Luster, AD Xavier, RJ AF Medoff, Benjamin D. Sandall, Barry P. Landry, Aimee Nagahama, Kiyotaka Mizoguchi, Atsushi Luster, Andrew D. Xavier, Ramnik J. TI Differential requirement for CARMA1 in agonist-selected T-cell development SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CARMA1; CD8 alpha alpha T cell; NKT cell; Treg ID KAPPA-B ACTIVATION; SIGNALING PATHWAY; NKT CELLS; RECEPTOR; SELF; KINASE; INFLAMMATION; COMPLEX; ANTIGEN; THYMUS AB Caspase recruitment domain-containing membrane-associated guanylate kinase protein-1 (CARMA1) is a critical component of the NF-kappa B signaling cascade mediated by TCR engagement. In addition to activation of naive T cells, TCR signaling is important for the development of agonist-selected T-cell subsets such as Treg, NKT cells, and CD8-alpha alpha T cells. However, little is known about the role of CARMA1 in the development of these lineages. Here we show that CARMA1-deficient mice (CARMA1(-/-)) have altered populations of specific subsets of agonist-selected T cells. Specifically, CARMA1(-/-) mice have impaired natural and adaptive Treg development, whereas NKT cell numbers are normal compared with wild-type mice. Interestingly, CD8-alpha alpha T cells, which may also be able to develop through an extrathymic selection pathway, are enriched in the gut of CARMA1(-/-) mice, whereas memory-phenotype CD4(+) T cells (CD62L(low)/CD44(high)) are present at reduced numbers in the periphery. These results indicate that CARMA1 is essential for Treg development, but is not necessary for the development of other agonist-selected T-cell subsets. Overall, these data reveal an important but differential role for CARMA1-mediated TCR signaling in T-cell development. C1 [Medoff, Benjamin D.; Sandall, Barry P.; Luster, Andrew D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Medoff, Benjamin D.; Sandall, Barry P.; Luster, Andrew D.] Harvard Univ, Sch Med, Charlestown, MA USA. [Medoff, Benjamin D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Medoff, Benjamin D.; Landry, Aimee; Nagahama, Kiyotaka; Mizoguchi, Atsushi; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Landry, Aimee; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Nagahama, Kiyotaka; Mizoguchi, Atsushi; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Nagahama, Kiyotaka] Massachusetts Gen Hosp, Dept Expt Pathol, Boston, MA 02114 USA. [Mizoguchi, Atsushi; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Medoff, BD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 149 13th St,CNY 8301, Charlestown, MA 02129 USA. EM bmedoff@partners.org FU National Institutes of Health [HL088297, DK64351, DK043351] FX This work was supported by grants from the National Institutes of Health (HL088297 to B.D.M. and R.JX, DK64351 to A.M., CCIB and DK043351 to R.J.X.). NR 49 TC 50 Z9 52 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2009 VL 39 IS 1 BP 78 EP 84 DI 10.1002/eji.200838734 PG 7 WC Immunology SC Immunology GA 400SW UT WOS:000262889900008 PM 19130560 ER PT J AU Papakostas, GI Fava, M AF Papakostas, George I. Fava, Maurizio TI Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Antidepressant; Placebo; Major; Depressive; Disorder; Adults ID DEPRESSION RATING-SCALE; MONTGOMERY-ASBERG; RELATIVE SENSITIVITY; DIAGNOSTIC CRITERIA; MAJOR DEPRESSION; RUN-IN; DISORDERS; SEVERITY; FOOD AB Substantial and highly variable placebo response rates represent a major obstacle to antidepressant development in major depressive disorder (MDD). However, whether the likelihood of receiving active treatment or placebo, a proxy of the degree of expectation of improvement, may itself influence clinical trial outcome is unclear. The goal of this work was to examine whether the probability of receiving placebo influences clinical trial outcome antidepressant MDD trials. Medline/Pubmed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD. 146 manuscripts involving 182 clinical trials were pooled (n = 36,385). Pooled response rates for drug and placebo were 53.8% and 37.3%. A meta-regression (random-effects) established that the probability of receiving placebo, year of publication, and baseline severity were independent predictors of the risk ratio of responding to antidepressants versus placebo. Specifically, a greater probability of receiving placebo, greater baseline severity and an earlier year of publication predicted greater antidepressant-placebo "efficacy separation". Fixed versus flexible dose design, trial duration and population age did not influence clinical trial outcome. (C) 2008 Elsevier B.V. and ECNP. All rights reserved. C1 [Papakostas, George I.; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 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 24 TC 167 Z9 170 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JAN PY 2009 VL 19 IS 1 BP 34 EP 40 DI 10.1016/j.euroneuro.2008.08.009 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 395ZX UT WOS:000262563100004 PM 18823760 ER PT J AU Boland, GWL Guimaraes, AS Mueller, PR AF Boland, Giles W. L. Guimaraes, Alexander S. Mueller, Peter R. TI The radiologist's conundrum: benefits and costs of increasing CT capacity and utilization - Opinion SO EUROPEAN RADIOLOGY LA English DT Editorial Material ID STRATEGIES; SAFETY C1 [Boland, Giles W. L.; Guimaraes, Alexander S.; Mueller, Peter R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Boland, Giles W. L.; Guimaraes, Alexander S.; Mueller, Peter R.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Boland, GWL (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM gboland@partners.org NR 19 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD JAN PY 2009 VL 19 IS 1 BP 9 EP 11 DI 10.1007/s00330-008-1159-7 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 396BU UT WOS:000262568000003 PM 18766347 ER PT J AU Restrepo, MI Mortensen, EM Waterer, GW Wunderink, RG Coalson, JJ Anzueto, A AF Restrepo, M. I. Mortensen, E. M. Waterer, G. W. Wunderink, R. G. Coalson, J. J. Anzueto, A. TI Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Antibiotics; community-acquired pneumonia; outcomes; sepsis ID COMMUNITY-ACQUIRED PNEUMONIA; BACTEREMIC PNEUMOCOCCAL PNEUMONIA; RESPIRATORY-TRACT INFECTIONS; BETA-LACTAM; ANTIMICROBIAL THERAPY; UNITED-STATES; CLARITHROMYCIN; EPIDEMIOLOGY; GUIDELINES; MANAGEMENT AB Recent studies suggest that macrolides may have beneficial effects for patients at risk for certain infections. The current authors examined the effect of macrolide therapy on 30-and 90-day mortality for patients with severe sepsis caused by pneumonia. A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had chest radiography consistent with, and had a discharge diagnosis of pneumonia and clinical criteria of severe sepsis. Subjects were considered to be on macrolides if they received at least one dose within 48 h of admission. Severe sepsis was present in 237 (30.1%) subjects, out of whom 104 (43.9%) received macrolides. Mortality was 20.3% at 30 days and 24.5% at 90 days. In the multivariable analysis, the use of macrolide was associated with decreased mortality at 30 days (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.2-0.7) and at 90 days (HR 0.3, 95% CI 0.2-0.6) in patients with severe sepsis and in patients with macrolide-resistant pathogens (HR 0.1, 95% CI 0.02-0.5). Macrolide use was associated with decreased mortality in patients with severe sepsis due to pneumonia and macrolide-resistant pathogens. Confirmatory studies are needed to determine whether macrolide therapy may be protective for patients with sepsis. C1 [Restrepo, M. I.; Mortensen, E. M.] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Vet Affairs Hosp, Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX 78229 USA. [Restrepo, M. I.; Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Coalson, J. J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Div Gen Med, San Antonio, TX 78229 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Waterer, G. W.] Univ Western Australia, Sch Med & Pharmacol, Royal Perth Hosp Unit, Perth, WA 6009, Australia. RP Restrepo, MI (reprint author), S Texas Vet Hlth Care Syst Audie L Murphy Div, VERDICT 1106, 7400 Menon Minter Blvd, San Antonio, TX 78229 USA. EM restrepo@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563; Wunderink, Richard/0000-0002-8527-4195 FU Howard Hughes Medical Institute [00378-001] NR 30 TC 90 Z9 93 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JAN PY 2009 VL 33 IS 1 BP 153 EP 159 DI 10.1183/09031936.00054108 PG 7 WC Respiratory System SC Respiratory System GA 430KM UT WOS:000264988000023 PM 18768577 ER PT J AU Isbarn, H Boccon-Gibod, L Carroll, PR Montorsi, F Schulman, C Smith, MR Sternberg, CN Studer, UE AF Isbarn, Hendrik Boccon-Gibod, Laurent Carroll, Peter R. Montorsi, Francesco Schulman, Claude Smith, Matthew R. Sternberg, Cora N. Studer, Urs E. TI Androgen Deprivation Therapy for the Treatment of Prostate Cancer: Consider Both Benefits and Risks SO EUROPEAN UROLOGY LA English DT Review DE Prostate cancer; Hormonal therapy; Adverse effects; Radical prostatectomy; Radiotherapy ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; BICALUTAMIDE 150 MG; MIDDLE-AGED MEN; HORMONE AGONIST TREATMENT; MEDIAN FOLLOW-UP; LEAN BODY-MASS; RADICAL PROSTATECTOMY; METABOLIC SYNDROME; CARDIOVASCULAR MORTALITY AB Context: Androgen deprivation therapy (ADT) is increasingly used for the treatment of prostate cancer (PCa), even in clinical settings in which there is no evidence-based proof of prolonged overall survival (OS). ADT, however, may be associated with numerous side effects, including an increased therapy-related cardiovascular mortality. Objective: To discuss different clinical settings in which ADT is currently used and to critically weigh the benefits of ADT against its possible side effects. Evidence acquisition: A MEDLINE search was conducted to identify original articles and review articles addressing the efficacy and side effects of ADT for the treatment of PCa. Keywords consisted of prostate cancer, hormonal therapy, adverse effects, radical prostatectomy, and radiotherapy. The articles with the highest level of evidence for the various examined end points were identified with the consensus of all authors and were reviewed. Evidence synthesis: Even short-term use of ADT may lead to numerous side effects, such as osteoporosis, obesity, sarcopenia, lipid alterations, insulin resistance, and increased risk for diabetes and cardiovascular morbidity. Despite these side effects, ADT is commonly used in various clinical settings in which a clear effect on improved OS has not been shown. Conclusions: ADT is associated with an increased risk of multiple side effects that may reduce quality of life and/or OS. Consequently, these issues should be discussed in detail with patients and their families before initiation of ADT. ADT should be used with knowledge of its potential long-term side effects and with possible lifestyle interventions, especially in settings with the highest risk-benefit ratio, to alleviate comorbidities. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Isbarn, Hendrik] Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, D-20246 Hamburg, Germany. [Boccon-Gibod, Laurent] Hop Xavier Bichat, Dept Urol, Paris, France. [Carroll, Peter R.] Univ San Francisco, Dept Urol, San Francisco, CA 94117 USA. [Montorsi, Francesco] Vita Salute San Raffaele, Dept Urol, Milan, Italy. [Schulman, Claude] Univ Clin Brussels, Erasme Hosp, Dept Urol, Brussels, Belgium. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Sternberg, Cora N.] San Camillo Forlanini Hosp, Dept Med Oncol, Rome, Italy. [Studer, Urs E.] Univ Hosp Bern, Dept Urol, Bern, Switzerland. RP Isbarn, H (reprint author), Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, Martinistr 52, D-20246 Hamburg, Germany. EM hendrikisbarn@gmail.com FU NCI NIH HHS [K24 CA121990-04, K24 CA121990-05, K24 CA121990] NR 105 TC 65 Z9 65 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JAN PY 2009 VL 55 IS 1 BP 62 EP 75 DI 10.1016/j.eururo.2008.10.008 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 389CB UT WOS:000262066700011 PM 18945543 ER PT J AU Xiang, ZM Reeves, SA AF Xiang, Zhongmin Reeves, Steven A. TI Simvastatin induces cell death in a mouse cerebellar slice culture (CSC) model of developmental myelination SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Statin; Toxicity; Cerebellar slice culture; Oligodendrocytes; Purkinje cells; Myelination; eGFP; Mevalonate; LDL; Isoprenylation ID CENTRAL-NERVOUS-SYSTEM; COA REDUCTASE INHIBITOR; COENZYME-A REDUCTASE; MULTIPLE-SCLEROSIS; IN-VITRO; GENE-EXPRESSION; CHOLESTEROL; STATINS; DISEASE; BRAIN AB Statins (inhibitors of HMG-CoA reductase) have shown promise in treating multiple sclerosis (MS). However, their effect on oligodendrocyte remyelination of demyelinated axons has not been clarified. Since developmental myelination shares many features with the remyelination process, we investigated the effect of lipophilic simvastatin on developmental myelination in organotypic cerebellar slice cultures (CSC). In this study, we first characterized developmental myelination in CSC from postnatal day (P)5 and P10 mice that express enhanced green fluorescence protein (eGFP) in oligodendrocyte-lineage cells. We then examined the effect of simvastatin on three developmental myelination stages: early myelination (115 CSC, 2DIV), late myelination (P10 CSC, 2DIV) and full myelination (P10 CSC, 10DIV). We found that treatment with simvastatin (0.1 mu M) for 6 days decreased the survival of Purkinje cells and oligodendrocytes drastically during the early myelination stage, while moderately during the late and full myelination stages. Oligodendrocytes are more resistant than Purkinje cells. The toxic effect of simvastatin could be rescued by the product of HMG-CoA reductase mevalonate but not low-density lipoprotein (LDL). Additionally, this toxic effect is independent of isoprenylation since farnesyl pyrophosphate (Fpp) but not geranylgeranyl pyrophosphate (GGpp) provided partial rescue. Our findings therefore suggest that inhibition of cholesterol synthesis is detrimental to neuronal tissue. (C) 2008 Elsevier Inc. All rights reserved. C1 [Xiang, Zhongmin; Reeves, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIND,CNS Signaling Lab, Charlestown, MA 02129 USA. RP Reeves, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIND,CNS Signaling Lab, 114 16th St, Charlestown, MA 02129 USA. EM zxiang1@partners.org; sreeves@partners.org FU NIH [R01 NS035996]; National Multiple Sclerosis Society (NMMS) [PP1359] FX This research was supported by grants from the NIH R01 NS035996 (SAR) and National Multiple Sclerosis Society (NMMS) PP1359 (SAR). The authors are grateful to Dr. Wendy Macklin (Lerner Research Institute, Cleveland, OH) for providing PLP-eGFP mice used in this Study. NR 44 TC 15 Z9 15 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2009 VL 215 IS 1 BP 41 EP 47 DI 10.1016/j.expneurol.2008.09.010 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 394QM UT WOS:000262462300005 PM 18929563 ER PT J AU Baker, BM Block, BL Rothchild, AC Walker, BD AF Baker, B. M. Block, B. L. Rothchild, A. C. Walker, B. D. TI Elite control of HIV infection: implications for vaccine design SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE acquired immune deficiency syndrome (AIDS); CD4(+)T cell; CD8(+)T cell; cell-mediated immunity; elite controller; human immunodeficiency virus (HIV); human leucocyte antigen (HLA); simian immunodeficiency virus (SIV); vaccine; viral load ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; LONG-TERM NONPROGRESSORS; NATURAL-KILLER-CELLS; MESSENGER-RNA LEVELS; DISEASE PROGRESSION; VIRAL LOAD; IMMUNE ACTIVATION; HLA-B; SEROPOSITIVE INDIVIDUALS AB Background: 'Elite controllers' are rare HIV-infected individuals who are able to spontaneously control HIV replication without medication, maintaining viral loads that are consistently below the limits of detection by currently available commercial assays. Objective: To examine studies of elite controllers that may elucidate mechanisms of HIV immune control useful in designing a vaccine. Methods: Recent literature on HIV controllers and studies that have evaluated aspects of viral and host immunology that correlate with viral control are examined. Results/conclusions: Although many elements of innate and adaptive immunity are associated with control of HIV infection, the specific mechanism(s) by which elite controllers achieve control remain undefined. Ongoing studies of elite controllers, including those examining host genetic polymorphisms, should facilitate the definition of an effective HIV-specific immune response and guide vaccine design. C1 [Baker, B. M.; Block, B. L.; Rothchild, A. C.; Walker, B. D.] Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Baker, B. M.; Block, B. L.; Rothchild, A. C.; Walker, B. D.] Harvard Univ, Sch Med, Div Aids, Charlestown, MA 02129 USA. [Walker, B. D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Walker, BD (reprint author), Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, 149 13th St,Room 5212D, Charlestown, MA 02129 USA. EM bwalker@partners.org FU NIH [A128568]; International AIDS Vaccine Initiative; Harvard University Center for AIDS Research FX This work was supported by grants from the NIH (A128568), the International AIDS Vaccine Initiative, and the Harvard University Center for AIDS Research. NR 129 TC 67 Z9 68 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JAN PY 2009 VL 9 IS 1 BP 55 EP 69 DI 10.1517/14712590802571928 PG 15 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 393BX UT WOS:000262347000006 PM 19063693 ER PT J AU Caplan, L Saag, KG AF Caplan, Liron Saag, Kenneth G. TI Glucocorticoids and the risk of osteoporosis SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE adverse effects; glucocorticoids; osteoporosis ID BONE-MINERAL DENSITY; CORTICOSTEROID-INDUCED OSTEOPOROSIS; VERTEBRAL FRACTURE RISK; RHEUMATOID-ARTHRITIS PATIENTS; RANDOMIZED CONTROLLED-TRIALS; RECEPTOR GENE POLYMORPHISMS; HIGH-DOSE GLUCOCORTICOIDS; ORAL CORTICOSTEROIDS; HIP FRACTURE; POSTMENOPAUSAL WOMEN AB Background: Glucocorticoid-induced osteoporosis (GIO) refers to a clinical condition in which a class of corticosteroids increases the susceptibility of bones to fracture. Numerous recent studies have improved our understanding of the underlying biology of this condition, whereas data from randomized controlled trials have provided clinicians with more options for prevention of GIO. Objective: To review the pathophysiology and epidemiology of GIO, as well as current pharmacologic treatment and prevention modalities available. To review the state of healthcare provider concordance with GIO prevention guidelines. Methods: Representative examples of various cellular and molecular processes underlying GIO were included, with an emphasis towards more recent discoveries. The data used to describe the epidemiology of GIO were derived from both randomized controlled studies and observational studies, framed through a discussion of known osteoporosis risk factors. Results/conclusion: Progress has been made in clarifying the pathophysiologic mechanisms that result in GIO. Although the options for preventions and treatment of GIO continue to expand, provider compliance with preventive measures remains suboptimal. C1 [Caplan, Liron] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80045 USA. [Saag, Kenneth G.] Univ Alabama Birmingham, Birmingham, AL USA. RP Caplan, L (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, POB 6511,B115, Denver, CO 80045 USA. EM liron.caplan@uchsc.edu NR 149 TC 19 Z9 23 U1 4 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 EI 1744-764X J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD JAN PY 2009 VL 8 IS 1 BP 33 EP 47 DI 10.1517/14740330802648194 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 401FW UT WOS:000262926300005 PM 19236216 ER PT J AU Kavirajan, H AF Kavirajan, Harish TI Memantine: a comprehensive review of safety and efficacy SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE age-associated memory impairment; alcohol dependence; Alzheimer's; amyotropic lateral sclerosis; attention deficit hyperactivity disorder; autism; bipolar disorder; cholinesterase inhibitor; cocaine dependence; dementia; frontotemporal dementia; glaucoma; headache; Huntington's disease; major depression; memantine; migraine; neuropathic pain; nicotine dependence; nystagmus; obsessive-compulsive disorder; opiate dependence; pervasive development disorder; phantom limb pain; pharmacology; postherpetic neuralgia; post-traumatic stress disorder; safety; schizophrenia; substance abuse; vascular dementia ID PLACEBO-CONTROLLED TRIAL; RECEPTOR ANTAGONIST MEMANTINE; OBSESSIVE-COMPULSIVE DISORDER; MODERATE ALZHEIMERS-DISEASE; MAJOR DEPRESSIVE DISORDER; OPEN-LABEL EXTENSION; PHANTOM LIMB PAIN; DOUBLE-BLIND; VASCULAR DEMENTIA; NMDA-RECEPTOR AB Background: Memantine is an uncompetitive antagonist of the N-methyl-D-aspartate glutamate receptor. It is now approved only for treatment of mode rate-to-severe Alzheimer's disease (AD). However, as a growing body of evidence indicates that disturbed glutamate neurotransmission may be central to the pathophysiology of such conditions as obesity, schizophrenia, depression, substance abuse, pain disorders and glaucoma, clinical trials have explored the role of memantine in these and other disorders. Objective: To provide a comprehensive review of the safety and efficacy of memantine across the range of clinical applications in which it has been studied. Methods: A search was done on Pubmed using keyword 'memantine' to identify clinical trials of memantine. Results/conclusion: At present, clinical trial evidence supports the use of memantine in only moderate-to-severe AD. Preliminary studies suggest benefit in frontotemporal dementia, alcohol dependence, post-traumatic stress disorder, headache and obesity, but rigorous clinical trials are needed to confirm these results. Available data indicate that across a range of clinical applications, memantine is a safe and well-tolerated drug. C1 [Kavirajan, Harish] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 92626 USA. [Kavirajan, Harish] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 92626 USA. RP Kavirajan, H (reprint author), VA Greater Los Angeles Healthcare Syst, 950 S Coast Dr,Ste 202, Los Angeles, CA 92626 USA. EM hkaviraj@gmail.com NR 83 TC 31 Z9 35 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD JAN PY 2009 VL 8 IS 1 BP 89 EP 109 DI 10.1517/14740330802528420 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 401FW UT WOS:000262926300010 PM 19236221 ER PT J AU Wen, PY AF Wen, Patrick Y. TI New developments in targeted molecular therapies for glioblastoma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material ID RECURRENT MALIGNANT GLIOMAS; BRAIN-TUMOR CONSORTIUM; PHASE-II; BEVACIZUMAB; INHIBITORS; GROWTH; VEGF; ANGIOGENESIS; MULTIFORME; IRINOTECAN C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org NR 34 TC 4 Z9 4 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD JAN PY 2009 VL 9 IS 1 BP 7 EP 10 DI 10.1586/14737140.9.1.7 PG 4 WC Oncology SC Oncology GA 396AN UT WOS:000262564700002 PM 19105702 ER PT J AU Zhu, AX Raymond, E AF Zhu, Andrew X. Raymond, Eric TI Early development of sunitinib in hepatocellular carcinoma SO Expert Review of Anticancer Therapy LA English DT Review DE antiangiogenesis; clinical trials; hepatocellular carcinoma; multitargeted receptor tyrosine kinase inhibitor; receptor tyrosine kinase; sunitinib; SUTENT (R) ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; FACTOR-RECEPTOR-ALPHA; PHASE-II TRIAL; ANTITUMOR-ACTIVITY; IN-VIVO; PROGNOSTIC-SIGNIFICANCE; TUMOR-GROWTH; CANCER; SU11248 AB Sunitinib malate is an oral, multitargeted receptor tyrosine kinase inhibitor of VEGF receptors 1, 2 and 3; PDGF receptors alpha and beta, and other receptor tyrosine kinases implicated in tumor growth, angiogenesis and metastasis. Hepatocellular carcinoma (HCC) is a highly vascular tumor that overexpresses several angiogenic factors; VEGF and PDGF signaling pathways play a key role in HCC. Until recently, treatment options for advanced HCC were limited and conventional therapies have met with poor response rates. Sorafenib provided proof-of-concept for molecularly targeted therapy in advanced HCC and has recently been approved for treatment. However, not all patients can tolerate sorafenib and patients may experience tumor progression; therefore, additional treatment options are warranted. Sunitinib has shown early evidence of anti-tumor activity in Phase II trials in US, European and Asian patients with locally advanced, unresectable and metastatic HCC. A Phase III trial of sunitinib in HCC is ongoing. C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02115 USA. [Raymond, Eric] Hop Beaujon, Beaujon Univ Hosp, F-92118 Clichy, France. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02115 USA. EM azhu@partners.org; eric.raymond@bjn.aphp.fr FU Pfizer; GlaxoSmithKline; Bayer; Amgen FX A Zhu discloses his role as an advisor to Pfizer, Bayer and Genentech. E Raymond discloses his role as an advisor to Pfizer and GlaxoSmithKline. Raymond has received honoraria from Pfizer and GlaxoSmithKline and has received research funding from Pfizer and Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript. Editorial assistance was provided by ACUMED (R)(Tytherington, UK) and was funded by Pfizer Inc. NR 60 TC 20 Z9 22 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD JAN PY 2009 VL 9 IS 1 BP 143 EP 150 DI 10.1586/14737140.9.1.143 PG 8 WC Oncology SC Oncology GA 396AN UT WOS:000262564700022 PM 19105714 ER PT J AU Snider, AJ Kawamori, T Bradshaw, SG Orr, KA Gilkeson, GS Hannun, YA Obeid, LM AF Snider, Ashley J. Kawamori, Toshihiko Bradshaw, Sarah G. Orr, K. Alexa Gilkeson, Gary S. Hannun, Yusuf A. Obeid, Lina M. TI A role for sphingosine kinase 1 in dextran sulfate sodium-induced colitis SO FASEB JOURNAL LA English DT Article DE sphingosine-1-phosphate; tumor necrosis factor alpha; cyclooxygenase-2; inflammation; ceramide ID INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; TNF-ALPHA; LYMPHOCYTE TRAFFICKING; COLON CARCINOGENESIS; ENDOTHELIAL-CELLS; COX-2 INHIBITOR; DENDRITIC CELLS; MICE; 1-PHOSPHATE AB The bioactive lipid sphingosine-1-phosphate (S1P) is emerging as an important mediator of immune and inflammatory responses. S1P formation is catalyzed by sphingosine kinase (SK), of which the SK1 isoenzyme is activated by tumor necrosis alpha (TNF-alpha). SK1 has been shown to be required for mediating TNF-alpha inflammatory responses in cells, including induction of cyclooxygenase 2 (COX-2). Because TNF-alpha and COX-2 are increased in patients with inflammatory bowel disease (IBD), we investigated the role of SK1 in a murine model of colitis. SK1(-/-) mice treated with dextran sulfate sodium (DSS) had significantly less blood loss, weight loss, colon shortening, colon histological damage, and splenomegaly than did wild-type (WT) mice. In addition, SK1(-/-) mice had no systemic inflammatory response. Moreover, WT but not SK1(-/-) mice treated with dextran sulfate sodium had significant increases in blood S1P levels, colon SK1 message and activity, and colon neutrophilic infiltrate. Unlike WT mice, SK1(-/-) mice failed to show colonic COX-2 induction despite an exaggerated TNF-alpha response; thus implicating for the first time SK1 in TNF-alpha-mediated COX-2 induction in vivo. Inhibition of SK1 may prove to be a valuable therapeutic target by inhibiting systemic and local inflammation in IBD.-Snider, A. J., Kawamori, T., Bradshaw, S. G., Orr, K. A., Gilkeson, G. S., Hannun, Y. A., Obeid, L. M. A role for sphingosine kinase 1 in dextran sulfate sodium-induced colitis. FASEB J. 23, 143-152 (2009) C1 [Snider, Ashley J.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Kawamori, Toshihiko] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Orr, K. Alexa] Med Univ S Carolina, Dept Mol & Cellular Biol & Pathobiol, Charleston, SC 29425 USA. [Hannun, Yusuf A.; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Bradshaw, Sarah G.; Gilkeson, Gary S.; Obeid, Lina M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,MSC 779, Charleston, SC 29425 USA. EM obeidl@musc.edu RI Kawamori, Toshihiko/G-7636-2012; OI obeid, lina/0000-0002-0734-0847 FU U.S. National Institutes of Health (NIH) [GM062887, C06 RR018823]; Veterans Affairs (VA) Merit Award; American College of Rheumatology Research and Education Foundation's FX This work was supported by U.S. National Institutes of Health (NIH) grant GM062887 and a Veterans Affairs (VA) Merit Award (L.M.O.) and by the American College of Rheumatology Research and Education Foundation's Within Our Reach: Finding a Cure for Arthritis campaign (G.S.G.). Lipid analysis was conducted by the Lipidomics Core at MUSC and was supported by NIH grant C06 RR018823. We thank Dr. Richard Proia (NIDDK, Bethesda, MD, USA) for supplying the SK1-/- mice; George Washington, DeAnna Baker, Samer Maalouf, and Tatsuya Kaneshiro for technical help; Margaret H. Romano and the Core Histology Laboratory for their technical assistance; Chris Clarke for careful examination of the manuscript; and Kathy Wiita-Fisk for her administrative assistance. NR 52 TC 77 Z9 80 U1 1 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 JAN PY 2009 VL 23 IS 1 BP 143 EP 152 DI 10.1096/fj.08-118109 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 389LZ UT WOS:000262095500017 PM 18815359 ER PT J AU Nadel, AS Likhite, ML AF Nadel, Allan S. Likhite, Marisa L. TI Impact of First-Trimester Aneuploidy Screening in a High-Risk Population SO FETAL DIAGNOSIS AND THERAPY LA English DT Article DE Fetal aneuploidy; First-trimester aneuploidy screening; First-trimester screening; Nuchal translucency ID FETAL NUCHAL-TRANSLUCENCY; DOWNS-SYNDROME; NASAL BONE; MATERNAL AGE; TRISOMY-21; GESTATION; TRIMESTER AB Objective: To determine the impact on maternal decision-making of offering first-trimester screening to women at increased risk for fetal aneuploidy. Methods: A retrospective chart review of all patients 6 35 years of age at delivery who registered to deliver at Massachusetts General Hospital before (2000-2002; n = 1,604) and after (2003-2005; n = 1,915) the introduction of first-trimester screening. Demographics, the choice of screening test and/or invasive procedure ( chorionic villus sampling or amniocentesis), and the detection rate of fetal aneuploidy were compared between the two groups by chi(2) test. Aneuploid newborns without an antenatal diagnosis were reviewed in detail. Results: The fraction of women who accepted prenatal screening and/or an invasive procedure increased from 1,122/1,604 (70%) to 1,751/1,915 (91%, p < 0.01) after the introduction of first-trimester screening. Fewer invasive procedures were done in the second time period, due to a decrease from 40 to 14% in the fraction of women going straight to an invasive procedure without screening ( p ! 0.01). Similar numbers of aneuploid fetuses were detected prenatally in the two time periods: 21/22 (95%) in the first time period and 22/25 (88%) in the second ( p = 0.36). All 4 cases not prenatally diagnosed involved the patient's decision to decline screening or ignore positive screening results. Conclusion: The introduction of first-trimester screening in a high-risk population was associated with an increase in the acceptance of prenatal screening and a reduction in the invasive procedure rate without a concomitant decrease in the detection of fetal aneuploidy. Copyright (C) 2009 S. Karger AG, Basel C1 [Nadel, Allan S.; Likhite, Marisa L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02215 USA. RP Nadel, AS (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Founders 4,55 Fruit St, Boston, MA 02215 USA. EM anadel@partners.org NR 14 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PY 2009 VL 26 IS 1 BP 29 EP 34 DI 10.1159/000236356 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 506KT UT WOS:000270774400006 PM 19816027 ER PT B AU Marcus, A Davidzon, G Law, D Verma, N Fletcher, R Khan, A Sarmenta, L AF Marcus, Adam Davidzon, Guido Law, Denise Verma, Namrata Fletcher, Rich Khan, Aamir Sarmenta, Luis BE Langer, J Ailisto, H Tuikka, T Grechenig, T Jacak, W Scharinger, J Madlmayr, G TI Using NFC-enabled Mobile Phones for Public Health in Developing Countries SO FIRST INTERNATIONAL WORKSHOP ON NEAR FIELD COMMUNICATION, PROCEEDINGS LA English DT Proceedings Paper CT 1st International Workshop on Near Field Communication (NFC 2009) CY FEB 24, 2009 CL Near Field Commun Res Lab, Campus Hagenberg, Hagenberg, AUSTRIA SP IEEE, Univ Appl Sci Upper Austria HO Near Field Commun Res Lab, Campus Hagenberg AB One of the largest IT challenges in the health and medical fields is the ability to track large numbers of patients and materials. As mobile phone availability becomes ubiquitous around the world, the use of Near Field Communication (NFC) with mobile phones is emerging as a promising solution to this challenge. The decreasing price and increasing availability of mobile phones and NFC allows us to to apply these technologies to developing countries in order to overcome patient identification and disease surveillance limitations, and permit improvements in data quality, patient referral, and emergency response. In this paper, we present a system using NFC-enabled mobile phones for facilitating the tracking and care of patients in a low-resource environment. While our system design has been inspired by the needs of an ongoing project in Karachi, Pakistan, we believe that it is easily generalizable and applicable for similar health and medical projects in other places where mobile service is available. C1 [Marcus, Adam; Law, Denise; Verma, Namrata; Fletcher, Rich; Sarmenta, Luis] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Davidzon, Guido] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Khan, Aamir] Interact Res & Dev, Karachi, Pakistan. RP Marcus, A (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM marcua@csail.mit.edu; gdavidzon@hms.harvard.edu; dytlaw@gmail.com; thesony@alum.mit.edu; fletcher@media.mit.edu; ajkhan@jhu.edu; lfgs@mit.edu FU NDSEG fellowship; NLM training [2T15LM007092-16] FX Some authors of this project were supported by an NDSEG fellowship and NLM training grant 2T15LM007092-16. NR 9 TC 9 Z9 9 U1 0 U2 4 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3577-7 PY 2009 BP 30 EP + DI 10.1109/NFC.2009.25 PG 2 WC Computer Science, Hardware & Architecture; Telecommunications SC Computer Science; Telecommunications GA BNP76 UT WOS:000275188000006 ER PT S AU Dickerson, BC AF Dickerson, Bradford C. BE Filippi, M TI fMRI in Neurodegenerative Diseases: From Scientific Insights to Clinical Applications SO FMRI TECHNIQUES AND PROTOCOLS SE Neuromethods LA English DT Article; Book Chapter DE Alzheimer's disease; Amyotrophic lateral sclerosis; Functional MRI; Huntington disease; Magnetic resonance imaging; Neurodegenerative diseases; Parkinson's disease ID MILD COGNITIVE IMPAIRMENT; EARLY ALZHEIMERS-DISEASE; DEEP BRAIN-STIMULATION; FUNCTIONAL MRI; PARKINSONS-DISEASE; WORKING-MEMORY; HUNTINGTONS-DISEASE; OLDER-ADULTS; NEURAL BASIS; LEWY BODIES AB fMRI is a technology with great promise as a tool to probe abnormalities of brain activity in neurode-generative diseases. The detection of functional brain abnormalities may be useful, in the appropriate clinical context, for early diagnosis, differential diagnosis, or prognostication. Prediction of response to treatment or therapeutic monitoring may also be possible with fMRI. In addition, fMRI has the potential to provide a variety of scientific insights that may have clinical relevance, including compensatory hyperactivation of brain circuits or genetic modulation of functional brain activity. C1 Massachusetts Gen Hosp, Gerontol Res Unit, Charlestown, MA 02129 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, Charlestown, MA 02129 USA. NR 127 TC 1 Z9 1 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-60327-918-5 J9 NEUROMETHODS JI Neuromethods PY 2009 VL 41 BP 657 EP 680 DI 10.1007/978-1-60327-919-2_22 D2 10.1007/978-1-60327-919-2 PG 24 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA BLA05 UT WOS:000269720800022 ER PT J AU Daines, SB Rohr, ES Pace, AP Fassbind, MJ Sangeorzan, BJ Ledoux, WR AF Daines, S. Bradley Rohr, Eric S. Pace, Andrew P. Fassbind, Michael J. Sangeorzan, Bruce J. Ledoux, William R. TI Cadaveric Simulation of a Pes Cavus Foot SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Pes Cavus; Foot Deformity; Foot Structure; Cadaver; Muscle Imbalance ID OSTEOTOMY; FEET AB Background: The pes cavus deformity has been well described in the literature; relative bony positions have been determined and specific muscle imbalances have been summarized. However, we are unaware of a cadaveric model that has been used to generate this foot pathology. The purpose of this study was to create such a model for future work on surgical and conservative treatment simulation. Materials and Methods: We used a custom designed, pneumatically actuated loading frame to apply forces to otherwise normal cadaveric feet while measuring bony motion as well as force beneath the foot. The dorsal tarsometatarsal and the dorsal intercuneiform ligaments were attenuated and three muscle imbalances, each similar to imbalances believed to cause the pes cavus deformity, were applied while bony motion and plantar forces were measured. Results: Only one of the muscle imbalances (overpull of the Achilles tendon, tibialis anterior, tibialis posterior, flexor hallucis longus and flexor digitorum longus) was successful at consistently generating the changes seen in pes cavus feet. This imbalance led to statistically significant changes including hindfoot inversion, talar dorsiflexion, medial midfoot plantar flexion and inversion, forefoot plantar flexion and adduction and an increase in force on the lateral mid- and forefoot. Conclusion: We have created a cadaveric model that approximates the general changes of the pes cavus deformity compared to normal feet. These changes mirror the general patterns of deformity produced by several disease mechanisms. Clinical Relevance: Future work will entail increasing the severity of the model and exploring various pes cavus treatment strategies. C1 [Ledoux, William R.] RR&D Ctr Excellence Limb Loss Prevent & Prosthet, VA Puget Sound, Seattle, WA 98108 USA. RP Ledoux, WR (reprint author), RR&D Ctr Excellence Limb Loss Prevent & Prosthet, VA Puget Sound, MS 151,1600 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU University of Washington School of Medicine; Department of Veterans Affairs, Rehabilitation RD Service [A2661C] FX This work was supported in part by the Medical Student Research and Training Program at the University of Washington School of Medicine, and the Department of Veterans Affairs, Rehabilitation R&D Service grant number A2661C. NR 20 TC 2 Z9 2 U1 0 U2 2 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD JAN PY 2009 VL 30 IS 1 BP 44 EP 50 DI 10.3113/FAI.2009.0044 PG 7 WC Orthopedics SC Orthopedics GA 390IC UT WOS:000262156500008 PM 19176185 ER PT J AU Shan, WH Oberley, TD AF Shan, Weihua Oberley, Terry D. TI Compartmental Redox Regulation of Androgen-Induced Prostate Cancer Cell Growth and Survival SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 16th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 18-22, 2009 CL San Francisco, CA SP Soc Free Rad Biol & Med C1 [Shan, Weihua; Oberley, Terry D.] Univ Wisconsin, Sch Med, Madison, WI 53706 USA. [Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2009 VL 47 BP S175 EP S175 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 522HM UT WOS:000271988500508 ER PT J AU Siedlak, SL Casadesus, G Webber, KM Pappolla, MA Atwood, CS Smith, MA Perry, G AF Siedlak, Sandra L. Casadesus, Gemma Webber, Kate M. Pappolla, Miguel A. Atwood, Craig S. Smith, Mark A. Perry, George TI Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease SO FREE RADICAL RESEARCH LA English DT Article DE Alzheimer's disease; amyloid-beta; antioxidant; R-alpha lipoic acid; transgenic mice ID ALPHA-LIPOIC-ACID; MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; TRANSGENIC MICE; LIPID-PEROXIDATION; MITOCHONDRIAL DYSFUNCTION; NEURODEGENERATIVE DISEASES; NEUROFIBRILLARY PATHOLOGY; LUTEINIZING-HORMONE; PROMINENT FEATURE AB Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-beta protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-beta load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and A beta PP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit. C1 [Perry, George] Univ Texas San Antonio, Coll Sci, San Antonio, TX 78249 USA. [Siedlak, Sandra L.; Webber, Kate M.; Smith, Mark A.; Perry, George] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Casadesus, Gemma] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. [Pappolla, Miguel A.] LSU Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA USA. [Atwood, Craig S.] Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Educ & Clin Ctr, Dept Med & Geriatr Res, Madison, WI USA. RP Perry, G (reprint author), Univ Texas San Antonio, Coll Sci, 1 UTSA Circle, San Antonio, TX 78249 USA. EM george.perry@utsa.edu RI Smith, Mark/A-9053-2009; Perry, George/A-8611-2009 OI Perry, George/0000-0002-6547-0172 FU National Institutes of Health; Alzheimer's Association; Philip Morris USA Inc.; Philip Morris International. FX Work in the authors' laboratories is supported by the National Institutes of Health, the Alzheimer's Association and Philip Morris USA Inc. and Philip Morris International. NR 86 TC 38 Z9 38 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2009 VL 43 IS 2 BP 156 EP 164 DI 10.1080/10715760802644694 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 405EB UT WOS:000263204400008 PM 19160110 ER PT J AU Yemisci, M Sinici, I Ozkara, HA Hayran, M Ay, H Celtikci, B Onder, E Buyukserbetci, G Kaya, EB Tokgozoglu, L Dalkara, T AF Yemisci, Muege Sinici, Incilay Ozkara, H. Asuman Hayran, Mutlu Ay, Hakan Celtikci, Basak Onder, Evren Buyukserbetci, Gulseren Kaya, E. Baris Tokgozoglu, Lale Dalkara, Turgay TI Protective role of 27bp repeat polymorphism in intron 4 of eNOS gene in lacunar infarction SO FREE RADICAL RESEARCH LA English DT Article DE eNOS gene; lacunar infarction; cerebral small vessel disease; polymorphisms; intron; VNTR ID NITRIC-OXIDE SYNTHASE; CORONARY-ARTERY-DISEASE; FLOW-MEDIATED VASODILATION; CEREBRAL-BLOOD-FLOW; ISCHEMIC-STROKE; TURKISH POPULATION; BEHCETS-DISEASE; GLU298ASP POLYMORPHISM; ASSOCIATION; HAPLOTYPES AB Association of the three potential endothelial nitric oxide synthase gene (eNOS) polymorphisms (T-786C in promoter region, G894T in exon 7 and tandem 27-bp repeats in intron 4) with an increased risk of lacunar infarction (LI) were investigated. Genotypes of 70 patients and 81 healthy controls were determined through PCR with or without RFLP. Flow-mediated dilatation (FMD) was performed to assess endothelial-dependent vasodilatation, whereas the endothelial-independent vasodilatation was assessed with nitroglycerin (NTG). Genotype distribution was significantly different between LI patients and controls for intron 4aa (alleles for four repeats), genotype frequency being 1.4% and 16.0%, respectively (odds ratio for additive effect, 0.47; 95% CI, 0.28-0.81; p=0.006). Haplotypes with the intron 4aa polymorphism were significantly higher in controls when compared with the LI group (p=0.001). Diminished FMD but normal NTG response confirmed that patients with LI have generalized endothelial dysfunction. Intron 4aa genotype of eNOS gene seems to be protective for isolated LI and the effect was potentiated by the absence of 786C polymorphism in any allele of the promoter region. C1 [Yemisci, Muege; Ay, Hakan; Buyukserbetci, Gulseren; Dalkara, Turgay] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. [Sinici, Incilay; Ozkara, H. Asuman; Celtikci, Basak; Onder, Evren] Hacettepe Univ, Fac Med, Dept Biochem, TR-06100 Ankara, Turkey. [Hayran, Mutlu] Hacettepe Univ, Fac Med, Dept Prevent Oncol, TR-06100 Ankara, Turkey. [Kaya, E. Baris; Tokgozoglu, Lale] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Kaya, E. Baris; Tokgozoglu, Lale] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Hacettepe Univ, Fac Med, Dept Cardiol, TR-06100 Ankara, Turkey. RP Dalkara, T (reprint author), Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. EM tdalkara@hacettepe.edu.tr RI YEMISCI, MUGE/I-9928-2013; LAY, INCILAY/I-8315-2013 OI LAY, INCILAY/0000-0002-1466-5746 NR 49 TC 17 Z9 19 U1 0 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2009 VL 43 IS 3 BP 272 EP 279 AR PII 908416294 DI 10.1080/10715760802691489 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423XW UT WOS:000264531100009 PM 19184759 ER PT S AU Jones, PB Bacskai, BJ Hyman, BT AF Jones, Phill B. Bacskai, Brian J. Hyman, Bradley T. BE Gadella, TWJ TI Biomedical FRET-FLIM applications SO FRET AND FLIM TECHNIQUES SE Laboratory Techniques in Biochemistry and Molecular Biology LA English DT Article; Book Chapter ID LIFETIME IMAGING MICROSCOPY; RECEPTOR-RELATED PROTEIN; VIVO FLUORESCENCE SPECTROSCOPY; AMYLOID PRECURSOR PROTEIN; RESONANCE ENERGY-TRANSFER; ALZHEIMERS-DISEASE; LIVING CELLS; CONFORMATIONAL-CHANGES; GLOBAL ANALYSIS; PHASE FLUOROMETER AB Over the past decade or so, technological and biological advances have led to enormous leaps forward in the area of biomedical microscopy. The introduction of affordable lifetime microscopy systems has enabled in situ measurements of protein dynamics with exquisite resolution, well beyond the limitations of diffraction limited optics. The most developed use for the technology is as a nanometer scale ruler for the detection and quantification of interactions and conformational changes of proteins, lipids, DNA, RNA, and other biologically important molecules. In addition, remote sensing of the local environment, including pH, O-2, and Ca2+ sensing, using custom designed biosensors, offers new insight into the cellular environment, function, and metabolism. As longer lifetime fluorophores are developed and more robust methods to suppress autofluorescence and other potential artifacts become available, it seems likely that FRET-FLIM will become an even more commonly used approach in biological sciences. In addition, the use of intrinsic tissue autofluorescence and exogenous disease-specific stains may offer the ability to noninvasively diagnose conditions as diverse as cancer and Alzheimer's disease, using endoscopes or tomography, in a clinical setting. C1 [Jones, Phill B.; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA. RP Jones, PB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA. NR 98 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0075-7535 BN 978-0-08-091512-8; 978-0-08-054958-3 J9 LAB TECH BIOCHEM MOL PY 2009 VL 33 BP 447 EP 474 DI 10.1016/S0075-7535(08)00011-9 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA3ZA UT WOS:000335187000012 ER PT B AU Oble, DA Hodi, FS Lauwers, GY Dranoff, G Mihm, MC AF Oble, Darryl A. Hodi, F. Stephen Lauwers, Gregory Y. Dranoff, Glenn Mihm, Martin C., Jr. BE Leong, SPL TI T-reg, Chemokines, and Other Small Molecules: Role in Metastasis and Its Prevention Experiences in Melanoma Immunobiology SO FROM LOCAL INVASION TO METASTATIC CANCER: INVOLVEMENT OF DISTANT SITES THROUGH THE LYMPHOVASCULAR SYSTEM SE Current Clinical Oncology Series LA English DT Article; Book Chapter DE TIL; melanoma; immunotherapy; CTLA-4; chemokine; immunobiology; metastasis; immunoregulation; T-reg; monoclonal antibody; adjuvant ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; CLINICAL STAGE-I; CUTANEOUS MALIGNANT-MELANOMA; ANTITUMOR IMMUNE-RESPONSE; PULSED DENDRITIC CELLS; HUMAN SOLID TUMORS; X-LINKED SYNDROME; CTLA-4 BLOCKADE; MONOCLONAL-ANTIBODY AB It has long been known that malignant tumors contain variable numbers of lymphocytes referred to as tumor-infiltrating lymphocytes (TIL). In melanoma, the intensity of this lymphocytic infiltrate is correlated with outcome measures, though there is some debate in the literature that such an association may only exist for certain melanomas, for example, of a certain thickness. However, early studies on melanoma TIL did not immunophenotype these cells, and recent data have revealed that the composition of the tumoral lymphocytic infiltrate is not homogenous, but rather represents varying contributions from many lymphocytic subsets. Furthermore, the function of CD8 TIL is often compromised as a result of the accumulation of immunoregulatory cells and various tumor escape mechanisms. Nevertheless, the increase in our understanding of immunobiology has facilitated the development of logical immunotherapeutic strategies to overcome such hurdles. Examples of these strategies which are currently being tested in clinical trials and which are discussed in-depth include blocking antibodies against CTLA-4 and therapies to deplete Foxp3(+) regulatory T cells (T-reg), which will hopefully enhance existing immunotherapeutical protocols such as tumor immunization. In addition to strategies designed to tip the balance between antitumor immunity and regulatory T-cell function, a greater understanding of the small molecules which govern the migration of immunocytes and tumor cells (chemokines) has made possible the development of strategies to selectively impede certain immunocyte populations into the tumor microenvironment, as well as to abrogate the chemokine-mediated metastasis of tumor cells. This chapter highlights some of these current developments occurring in the field of immunological cancer therapy, and illustrates how these developments resulted from a greater understanding of basic immunobiology. C1 [Oble, Darryl A.] Univ Chicago, Med Ctr, Dermatol Sect, Chicago, IL 60637 USA. [Lauwers, Gregory Y.; Mihm, Martin C., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Hodi, F. Stephen; Dranoff, Glenn] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Oble, DA (reprint author), Univ Chicago, Med Ctr, Dermatol Sect, Chicago, IL 60637 USA. NR 156 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-086-1 J9 CURR CLIN ONCOL PY 2009 BP 263 EP 279 DI 10.1007/978-1-60327-087-8_24 D2 10.1007/978-1-60327-087-8 PG 17 WC Oncology SC Oncology GA BKF24 UT WOS:000267947100025 ER PT J AU Radant, AD Dobie, DJ Peskind, ER Murburg, MM Petrie, EC Kanter, ED Raskind, MA Wilkinson, CW AF Radant, Allen D. Dobie, Dorcas J. Peskind, Elaine R. Murburg, M. Michele Petrie, Eric C. Kanter, Evan D. Raskind, Murray A. Wilkinson, Charles W. TI Adrenocortical responsiveness to infusions of physiological doses of ACTH is not altered in posttraumatic stress disorder SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE PTSD; HPA axis; ACTH; adrenal responsiveness; cortisol; DHEA; human ID PITUITARY-ADRENAL AXIS; AGE-RELATED-CHANGES; 1 MU-G; FEEDBACK INHIBITION; SALIVARY CORTISOL; PLASMA ADRENOCORTICOTROPIN; HEALTHY-SUBJECTS; COMBAT VETERANS; SYNACTHEN TEST; PTSD AB Early studies of posttraumatic stress disorder (PTSD) reported that abnormal function of the hypothalamic-pituitary-adrenocortical (HPA) system was associated with the disorder. However, subsequent studies attempting to identify a specific aspect of HPA dysfunction that characterizes PTSD have been marked by considerable inconsistency of results. A facet of HPA regulation that has been considered but not definitively investigated is the possibility that the responsiveness of the adrenal cortex to physiological concentrations of adrenocorticotropin (ACTH) is diminished in PTSD. Relationships between PTSD and the adrenal androgen dehydroepiandrosterone (DHEA) have also been postulated. In this study we investigated the magnitude and time course of changes in concentrations of plasma cortisol and DHEA in response to bolus infusions of physiological doses of ACTH(1-24) in PTSD patients and control subjects. We found no evidence for PTSD-related alterations in cortisol or DHEA secretion in response to stimulation by low doses of ACTH and conclude that adrenocortical responsiveness is normal in PTSD. Results from this and other studies suggest that the occurrence of defects in HPA function in PTSD may be specific responses to particular combinations of trauma type, genetic susceptibility, and individual history. C1 [Radant, Allen D.; Dobie, Dorcas J.; Peskind, Elaine R.; Petrie, Eric C.; Kanter, Evan D.; Raskind, Murray A.] VA Puget Sound Hlth Care Syst, Northwest Network, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA 98108 USA. [Radant, Allen D.; Dobie, Dorcas J.; Peskind, Elaine R.; Petrie, Eric C.; Kanter, Evan D.; Raskind, Murray A.; Wilkinson, Charles W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Wilkinson, Charles W.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Wilkinson, CW (reprint author), VA Puget Sound Hlth Care Syst, Northwest Network, VISN Mental Illness Res Educ & Clin Ctr 20, S-182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM wilkinso@u.washington.edu FU Northwest Network VISN 20 Mental Illness Research; Education and Clinical Center (MIRECC); VA Puget Sound Geriatric Research; Education and Clinical Center (GRECC); Office of Research and Development Medical Research Service, Department of Veterans Affairs FX For their excellent assistance that made this study possible, we thank Jane Hammett RN, and Jennifer Acselrod RN, for nursing care of study participants, Jill Perander, Robert Beckham III, Shawna Feely, and Kristina Purganan for recruitment and study coordination, Libby Colasurdo and Carl Sikkema for hormone assays, Molly Chinn for assistance in preparing ACTH doses, and Nadia Czajkiewicz for graphic design. This material is based upon work supported by the Northwest Network VISN 20 Mental Illness Research, Education and Clinical Center (MIRECC), the VA Puget Sound Geriatric Research, Education and Clinical Center (GRECC), and the Office of Research and Development Medical Research Service, Department of Veterans Affairs. NR 65 TC 5 Z9 5 U1 1 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PY 2009 VL 3 AR 40 DI 10.3389/neuro.08.040.2009 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V18VE UT WOS:000208031500039 PM 19893760 ER PT J AU Ng, CY Madsen, JC Rosengard, BR Allan, JS AF Ng, Choo Y. Madsen, Joren C. Rosengard, Bruce R. Allan, James S. TI Immunosuppression for lung transplantation SO FRONTIERS IN BIOSCIENCE LA English DT Review DE Lung; Transplantation; Immunosuppression; Allorecognition; Tolerance; Review ID REGULATORY T-CELLS; BRONCHIOLITIS OBLITERANS SYNDROME; CADAVERIC RENAL-TRANSPLANTATION; CARDIAC ALLOGRAFT VASCULOPATHY; SOLID-ORGAN TRANSPLANTATION; DENDRITIC CELLS; MYCOPHENOLATE-MOFETIL; INDIRECT RECOGNITION; CHRONIC REJECTION; IN-VIVO AB As a result of advances in surgical techniques, immunosuppressive therapy, and postoperative management, lung transplantation has become an established therapeutic option for individuals with a variety of end-stage lung diseases. The current 1-year actuarial survival rate following lung transplantation is approaching 80%. However, the 5- year actuarial survival rate has remained virtually unchanged at approximately 50% over the last 15 years due to the processes of acute and chronic lung allograft rejection (1). Clinicians still rely on a vast array of immunosuppressive agents to suppress the process of graft rejection, but find themselves limited by an inescapable therapeutic paradox. Insufficient immunosuppression results in graft loss due to rejection, while excess immunosuppression results in increased morbidity and mortality from opportunistic infections and malignancies. Indeed, graft rejection, infection, and malignancy are the three principal causes of mortality for the lung transplant recipient. One should also keep in mind that graft loss in a lung transplant recipient is usually a fatal event, since there is no practical means of long-term mechanical support, and since the prospects of re-transplantation are low, given the shortage of acceptable donor grafts. This chapter reviews the current state of immunosuppressive therapy for lung transplantation and suggests alternative paradigms for the management of future lung transplant recipients. C1 [Ng, Choo Y.; Madsen, Joren C.; Rosengard, Bruce R.; Allan, James S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Ng, Choo Y.; Madsen, Joren C.; Rosengard, Bruce R.; Allan, James S.] Harvard Univ, Sch Med, Boston, MA USA. [Madsen, Joren C.; Rosengard, Bruce R.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [Allan, James S.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM jallan@partners.org FU National Institute of Health [R01HL054211, R01HL67110, R01HL071932, P01HL8646]; National Institute of Allergy and Infectious Disease [U19AI066705, P01AI50157]; American Surgical Association Foundation; Thoracic Surgical Foundation for Research and Education FX This work was supported in part by National Institute of Health grants from the National Heart, Lung and Blood Institute (R01HL054211, R01HL67110, R01HL071932, P01HL8646) and the National Institute of Allergy and Infectious Disease (U19AI066705, P01AI50157), and by awards from the American Surgical Association Foundation, and the Thoracic Surgical Foundation for Research and Education. NR 110 TC 7 Z9 7 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2009 VL 14 BP 1627 EP 1641 DI 10.2741/3330 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 393DZ UT WOS:000262352400103 PM 19273152 ER PT S AU Chan, AW Liebsch, NJ Trofimov, A AF Chan, Annie W. Liebsch, Norbert J. Trofimov, Alexei BE Harari, PM Connor, NP Grau, C TI Advantages of Proton Beam Therapy in Functional Preservation and Quality of Life in Head and Neck Radiotherapy SO FUNCTIONAL PRESERVATION AND QUALITY OF LIFE IN HEAD AND NECK RADIOTHERAPY SE Medical Radiology-Radiation Oncology LA English DT Article; Book Chapter ID ADENOID-CYSTIC CARCINOMA; MODULATED RADIATION-THERAPY; PARANASAL SINUS CANCER; NASAL CAVITY; OROPHARYNGEAL CARCINOMA; MALIGNANCIES; EXPERIENCE; PHOTON; IRRADIATION; SURGERY C1 [Chan, Annie W.; Liebsch, Norbert J.; Trofimov, Alexei] Harvard Univ, Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Dept Radiat Oncol,Med Sch, Boston, MA 02114 USA. RP Chan, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Dept Radiat Oncol,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM awchan@partners.org NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-73231-0 J9 MED RADIOL RADIAT ON PY 2009 BP 155 EP 161 DI 10.1007/978-3-540-73232-7_13 D2 10.1007/978-3-540-73232-7 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BKI50 UT WOS:000268211600013 ER PT J AU Lerman, I Lopez-Poncea, A Villa, AR Escobedo, M Caballero, EA Velasco, ML Gomez-Perez, FJ Rull-Rodrigo, JA AF Lerman, Israel Lopez-Poncea, Alfredo Villa, Antonio R. Escobedo, Michelle Caballero, Enrique A. Velasco, Maria Luisa Gomez-Peez, Francisco Javier Rull-Rodrigo, Juan Antonio TI Pilot study of two different strategies to reinforce self care behaviors and treatment compliance among type 2 diabetes patients from low income strata. SO GACETA MEDICA DE MEXICO LA Spanish DT Article DE Reinforcement strategies; diabetes self-management ID MANAGEMENT EDUCATION; METABOLIC CONTROL; PROGRAM; INTERVENTIONS; COMPLICATIONS; OUTPATIENT; ADHERENCE; IMPROVE; PEOPLE; TRIALS AB Long term diabetes self-management behaviors, and strict glycemic control are difficult to achieve in clinical practice. Objective: Asesss No different reinforcement strategies for diabetes self care management, psychological distress and glycemic control in a one year follow, up study. Methods: 70 consecutive type 2 diabetic patients, were recruited and randomly assigned to three study groups. Subjects in the control group (CG) continued with their normal treatment schedule. The second group received a reinforcement course at 6 months (RCG) and in the third group, patients were contacted monthly hi phone (PHCG) to promote self-management attitudes and address problems as the-v arose. A battery, of questions and laboratory work-up were obtained at baseline and at one year follow-up. Results: At one year follow-up, the three groups significantly increased their diabetes-related knowledge. Both experimental groups displayed improved treatment compliance and had better adherence to the recommended meal plan (p=0.06 and 0.003). In addition, the PHCG significantly increased (p < 0.0001) their adherence to pharmacological treatment. No significant differences were observed in glycemic control, prevalence of depression or diabetes related distress. Conclusions: Follow-up patient reinforcement strategies improve strategic diabetic self-care management behaviors. Further studies needed to demonstrate the positive impact of these benefits on diabetes related outcomes. C1 [Lerman, Israel; Lopez-Poncea, Alfredo; Velasco, Maria Luisa; Gomez-Peez, Francisco Javier; Rull-Rodrigo, Juan Antonio] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Mexico City 14000, DF, Mexico. [Villa, Antonio R.; Escobedo, Michelle] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unidad Epidemiol Clin, Mexico City 14000, DF, Mexico. [Caballero, Enrique A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Latino Diabet Initivat, Boston, MA 02115 USA. RP Lerman, I (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Vasco de Quiroga 15,Col Sector 16, Mexico City 14000, DF, Mexico. EM israellerman@gmail.com NR 29 TC 6 Z9 7 U1 1 U2 6 PU ACAD NACIONAL MEDICINA MEXICO PI MEXICO PA CENTRO MEDICO NACIONAL SIGLO XXI, UNIDAD CONGRESOS, GLOQUE B, PROMER PISO, MEXICO, DF 06725, MEXICO SN 0016-3813 J9 GAC MED MEX JI Gac. Med. Mex. PD JAN-FEB PY 2009 VL 145 IS 1 BP 15 EP 19 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 409IU UT WOS:000263500200003 PM 19256406 ER PT J AU Lanford, RE Evans, MJ Lohmann, V Lindenbach, B Gale, M Rehermann, B Chang, KM Lemon, SM AF Lanford, Robert E. Evans, Matthew J. Lohmann, Volker Lindenbach, Brett Gale, Michael, Jr. Rehermann, Barbara Chang, Kyong-Mi Lemon, Stanley M. TI The Accelerating Pace of HCV Research: A Summary of the 15th International Symposium on Hepatitis C Virus and Related Viruses SO GASTROENTEROLOGY LA English DT Editorial Material C1 Univ Texas Med Branch, Inst Human Infect & Immun, 6200 Galveston Natl Lab, Galveston, TX 77555 USA. Southwest Fdn Biomed Res, San Antonio, TX USA. Mt Sinai Sch Med, Dept Microbiol, New York, NY USA. Univ Heidelberg, Dept Molec Virol, Heidelberg, Germany. Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT USA. Univ Washington, Dept Immunol, Seattle, WA USA. NIDDKD, Liver Dis Branch, Immunol Sect, Bethesda, MD USA. Univ Penn, Philadelphia, PA USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Lemon, SM (reprint author), Univ Texas Med Branch, Inst Human Infect & Immun, 6200 Galveston Natl Lab, 301 Univ Blvd, Galveston, TX 77555 USA. EM smlemon@utmb.edu OI Lohmann, Volker/0000-0001-8719-7608; Gale, Michael/0000-0002-6332-7436; Evans, Matthew/0000-0002-4991-3877 FU Intramural NIH HHS; NCI NIH HHS [K01 CA107092, K01-CA107092]; NIAID NIH HHS [R01-AI060389, K99 AI077800, K99-AI077800, R01 AI047519, R01 AI060389, R01-AI47519, U19 AI040035, U19-AI040035]; NIDA NIH HHS [R01 DA024563] NR 0 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2009 VL 136 IS 1 BP 9 EP 16 DI 10.1053/j.gastro.2008.11.019 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 388OG UT WOS:000262028500045 PM 19026648 ER PT J AU Bernards, A Settleman, J AF Bernards, Andre Settleman, Jeffrey TI Loss of the Ras Regulator RASAL1: Another Route to Ras Activation in Colorectal Cancer SO GASTROENTEROLOGY LA English DT Editorial Material ID ABERRANT PROMOTER METHYLATION; PROTEIN HDAB2IP GENE; PROSTATE-CANCER; NOONAN-SYNDROME; MUTATIONS; TUMOR; EXPRESSION; CARCINOMA; BREAST C1 [Bernards, Andre; Settleman, Jeffrey] Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. RP Bernards, A (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM abernard@helix.mgh.harvard.edu RI Xie, Huangming/B-2260-2012 NR 23 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2009 VL 136 IS 1 BP 46 EP 48 DI 10.1053/j.gastro.2008.11.024 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 388OG UT WOS:000262028500011 PM 19041648 ER PT J AU Bronner, MP Overholt, BF Taylor, SL Haggitt, RC Wang, KK Burdick, JS Lightdale, CJ Kimmey, M Nava, HR Sivak, MV Nishioka, N Barr, H Canto, MI Marcon, N Pedrosa, M Grace, M Depot, M AF Bronner, Mary P. Overholt, Bergen F. Taylor, Shari L. Haggitt, Rodger C. Wang, Kenneth K. Burdick, J. Steven Lightdale, Charles J. Kimmey, Michael Nava, Hector R. Sivak, Michael V. Nishioka, Norman Barr, Hugh Canto, Marcia I. Marcon, Norman Pedrosa, Marcos Grace, Michael Depot, Michelle CA Int Photodynamic Therapy Grp High- TI Squamous Overgrowth Is Not a Safety Concern for Photodynamic Therapy for Barrett's Esophagus With High-Grade Dysplasia SO GASTROENTEROLOGY LA English DT Article ID ENDOSCOPIC MUCOSAL RESECTION; EARLY CANCER; 5-AMINOLEVULINIC ACID; EARLY ADENOCARCINOMA; PLASMA COAGULATION; FOLLOW-UP; ABLATION; REEPITHILIALIZATION; ABNORMALITIES; PREDICTORS AB Background & Aims: Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barretes esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. Methods: Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n = 138) or 20 mg omeprazole twice daily (n = 70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. Results: Histologic assessment of 33,658 biopsies showed no significant difference (P > .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. Conclusions: No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia. in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma. C1 [Bronner, Mary P.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44195 USA. [Overholt, Bergen F.] Thompson Canc Survival Ctr, Knoxville, TN USA. [Taylor, Shari L.] Caris Diagnost, Irving, TX USA. [Haggitt, Rodger C.; Kimmey, Michael] Univ Washington, Seattle, WA 98195 USA. [Wang, Kenneth K.] Mayo Clin, Rochester, MN USA. [Burdick, J. Steven] Parkland Mem Hosp & Affiliated Inst, Dallas, TX USA. [Lightdale, Charles J.] Columbia Presbyterian Med Ctr, New York, NY USA. [Nava, Hector R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Sivak, Michael V.] Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. [Nishioka, Norman] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barr, Hugh] Gloucestershire Royal Hosp, Gloucester, England. [Canto, Marcia I.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Marcon, Norman] Univ Toronto, Wellesley Hosp, Toronto, ON M4Y 1J3, Canada. [Pedrosa, Marcos] Boston VA Med Ctr, Boston, MA USA. [Grace, Michael] Univ Alberta, Edmonton, AB, Canada. [Depot, Michelle] Axcan Pharma, Mt St Hilaire, PQ, Canada. RP Bronner, MP (reprint author), Cleveland Clin, Dept Anat Pathol, L25,9500 Euclid Ave, Cleveland, OH 44195 USA. EM bronnem@ccf.org RI Barr, Hugh/G-4673-2014 OI Barr, Hugh/0000-0002-2919-5660 NR 37 TC 36 Z9 36 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2009 VL 136 IS 1 BP 56 EP 64 DI 10.1053/j.gastro.2008.10.012 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 388OG UT WOS:000262028500013 PM 18996379 ER PT J AU Strate, LL Liu, YL Aldoori, WH Syngal, S Giovannucci, EL AF Strate, Lisa L. Liu, Yan L. Aldoori, Walid H. Syngal, Sapna Giovannucci, Edward L. TI Obesity Increases the Risks of Diverticulitis and Diverticular Bleeding SO GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MALE HEALTH-PROFESSIONALS; BODY-MASS INDEX; PHYSICAL-ACTIVITY; GASTROINTESTINAL SYMPTOMS; UNITED-STATES; DISEASE; COLON; MEN; POPULATION AB Background & Aims: Studies of obesity and diverticular complications are limited. We assessed the relationship between body mass index (BMI), waist circumference, and waist-to-hip ratio and diverticulitis and diverticular bleeding. Methods: A prospective cohort study of 47,228 male health professionals (40-75 years old) who were free of diverticular disease in 1986 (baseline) was performed. Men reporting newly diagnosed diverticular disease on biennial follow-up questionnaires were sent supplemental questionnaires. Weight was recorded every 2 years, and data on waist and hip circumferences were collected in 1987. Results: We documented 801 incident cases of diverticulitis and 383 incident cases of diverticular bleeding during 18 years of follow-up. After adjustment for other risk factors, men with a BMI >= 30 kg/m(2) had a relative risk (RR) of 1.78 (95% confidence interval [CI], 1.08-2.94) for diverticulitis and 3.19 (95% CI, 1.45-7.00) for diverticular bleeding compared with men with a BMI of < 21 kg/m(2). Men in the highest quintile of waist circumference, compared with those in the lowest, had a multivariable RR of 1.56 (95% CI, 1.18-2.07) for diverticulitis and 1.96 (95% CI, 1.30-2.97) for diverticular bleeding. Waist-to-hip ratio was also associated with the risk of diverticular complications when the highest and lowest quintiles were compared, with a multivariable RR of 1.62 (95% CI, 1.23-2.14) for diverticulitis and 1.91 (95% CI, 1.26-2.90) for diverticular bleeding, Adjustment for BMI did not change the associations seen for waist-to-hip ratio. Conclusions: In this large prospective cohort, BMI, waist circumference, and waist-to-hip ratio significantly increased the risks of diverticulitis and diverticular bleeding. C1 [Strate, Lisa L.] Univ Washington, Harborview Med Ctr, Dept Med, Div Gastroenterol, Seattle, WA 98104 USA. [Strate, Lisa L.] Univ Washington, Sch Med, Seattle, WA 98104 USA. [Liu, Yan L.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Aldoori, Walid H.] Wyeth Consumer Healthcare Inc, Mississauga, ON, Canada. [Syngal, Sapna; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Strate, LL (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Gastroenterol, 325 9th Ave,Box 359773, Seattle, WA 98104 USA. EM lisas@medicine.washington.edu FU Agency for Healthcare Research and Quality [K08 HS14062]; National Cancer Institute [PO1CA055075, K24 CA113433]; National Heart, Lung, and Blood Institute [R01 HL035464] FX Supported by grants from the Agency for Healthcare Research and Quality (K08 HS14062 to L.L.S.), the National Cancer Institute (PO1CA055075 to E.L.G. and K24 CA113433 to S.S.), and the National Heart, Lung, and Blood Institute (R01 HL035464 to E.L.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institutes of Health, or the Agency for Healthcare Research and Quality. The funding sources had no role in the design, conduct, or reporting of this study. NR 52 TC 125 Z9 130 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2009 VL 136 IS 1 BP 115 EP 122 DI 10.1053/j.gastro.2008.09.025 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 388OG UT WOS:000262028500019 PM 18996378 ER PT J AU Lok, AS Seeff, LB Morgan, TR Di Bisceglie, AM Sterling, RK Curto, TM Everson, GT Lindsay, KL Lee, WM Bonkovsky, HL Dienstag, JL Ghany, MG Morishima, C Goodman, ZD AF Lok, Anna S. Seeff, Leonard B. Morgan, Timothy R. Di Bisceglie, Adrian M. Sterling, Richard K. Curto, Teresa M. Everson, Gregory T. Lindsay, Karen L. Lee, William M. Bonkovsky, Herbert L. Dienstag, Jules L. Ghany, Marc G. Morishima, Chihiro Goodman, Zachary D. CA HALT-C Trial Grp TI Incidence of Hepatocellular Carcinoma and Associated Risk Factors in Hepatitis C-Related Advanced Liver Disease SO GASTROENTEROLOGY LA English DT Article ID SUSTAINED VIROLOGICAL RESPONSE; INTERFERON THERAPY; NATURAL-HISTORY; VIRUS-INFECTION; UNITED-STATES; FOLLOW-UP; CIRRHOSIS; FIBROSIS; TRIAL; HEPATOCARCINOGENESIS AB Background & Aims: Although the incidence of hepatocellular carcinoma (HCC) is increasing in the United States, data from large prospective studies are limited. We evaluated the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) cohort for the incidence of HCC and associated risk factors. Methods: Hepatitis C virus-positive patients with bridging fibrosis or cirrhosis who did not respond to peginterferon and ribavirin were randomized to groups that were given maintenance peginterferon for 3.5 years or no treatment. HCC incidence was determined by Kaplan-Meier analysis, and baseline factors associated with HCC were analyzed by Cox regression. Results: 1,005 patients (mean age, 50.2 years; 71% male; 72% white race) were studied; 59% had bridging fibrosis, and 41% had cirrhosis. During a median follow-up of 4.6 years (maximum, 6.7 years), HCC developed in 48 patients (4.8%). The cumulative 5-year HCC incidence was similar for peginterferontreated patients and controls, 5.4% vs 5.0%, respectively (P = .78), and was higher among patients with cirrhosis than those with bridging fibrosis, 7.0% vs 4.1%, respectively (P = .08). HCC developed in 8 (17%) patients whose serial biopsy specimens showed only fibrosis. A multivariate analysis model comprising older age, black race, lower platelet count, higher alkaline phosphatase, esophageal varices, and smoking was developed to predict the risk of HCC. Conclusions: We found that maintenance peginterferon did not reduce the incidence of HCC in the HALT-C cohort. Baseline clinical and laboratory features predicted risk for HCC. Additional studies are required to confirm our finding of HCC in patients with chronic hepatitis C and bridging fibrosis. C1 [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Seeff, Leonard B.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Med Serv, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Div Hepat Pathol, Washington, DC 20306 USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Vet Adm Special Reference Lab Pathol, Washington, DC 20306 USA. RP Lok, AS (reprint author), Univ Michigan Hosp, Div Gastroenterol, 3912 Taubman Ctr,SPC 5362, Ann Arbor, MI 48109 USA. EM aslok@umich.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health; Cooperative Research and Development Agreement (CRADA) FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed in Appendix 1); the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute; the National Center for Minority Health and Health Disparities; General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed In Appendix 1); and by Hoffman-La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 54 TC 262 Z9 270 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2009 VL 136 IS 1 BP 138 EP 148 DI 10.1053/j.gastro.2008.09.014 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 388OG UT WOS:000262028500022 PM 18848939 ER PT J AU Chung, CH Shugrue, C Nagar, A Doll, JA Cornwell, M Gattu, A Kolodecik, T Pandol, SJ Gorelick, F AF Chung, Chuhan Shugrue, Christine Nagar, Anil Doll, Jennifer A. Cornwell, Mona Gattu, Arijeet Kolodecik, Tom Pandol, Stephen J. Gorelick, Fred TI Ethanol Exposure Depletes Hepatic Pigment Epithelium-Derived Factor, a Novel Lipid Regulator SO GASTROENTEROLOGY LA English DT Article ID ALCOHOLIC LIVER-DISEASE; STELLATE CELL ACTIVATION; MATRIX METALLOPROTEINASES; SECRETED PROTEINS; FATTY LIVER; PPAR-ALPHA; IDENTIFICATION; STEATOSIS; FIBROSIS; DIFFERENTIATION AB Background & Aims: Ethanol abuse can lead to hepatic steatosis and evolve into cirrhosis and hepatocellular carcinoma. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein. that is expressed by hepatocytes. Proteomic, experimental, and clinical studies implicate PEDF's role in lipid regulation. Because matrix metalloproteinase (MMP)-2/9 activity regulates PEDF levels, we investigated whether PEDF degradation by MMPs has a permissive role in ethanol-induced hepatic steatosis. Methods: PEDF levels were examined in liver biopsy specimens from patients with ethanol-induced steatosis. Hepatic PEDF levels and MMP activity were assessed in 2 animal models of ethanol feeding (rats on an alcohol-containing liquid diet and mice given intragastric infusion of ethanol). The consequences of PEDF depletion in the liver were examined in PEDF-null mice. Results: Liver biopsy samples from patients with ethanol-induced steatosis had reduced PEDF levels, compared with normal liver samples. Ethanol-fed animals had histologic steatosis and increased liver triglyceride content (P < .05), as well as reduced levels of hepatic PEDF and increased MMP-2/9 activity. Ethanol-exposed hepatic lysates degraded PEDF in a MMP-2/9-dependent manner, and liver sections demonstrated abundant MMP-2/9 activity in situ. Addition of recombinant PEDF to PEDF-null hepatocytes, reduced their triglyceride content. Conclusions: Ethanol exposure leads to marked loss of hepatic PEDF in human livers and in 2 animal models of ethanol feeding. Loss of PEDF contributes to the accumulation of lipids in ethanol-induced hepatic steatosis. C1 [Chung, Chuhan; Shugrue, Christine; Nagar, Anil; Gattu, Arijeet; Kolodecik, Tom; Gorelick, Fred] Yale Univ, Sch Med, Dept Med, Sect Digest Dis, New Haven, CT 06510 USA. [Chung, Chuhan; Nagar, Anil; Gorelick, Fred] VA Connecticut Healthcare Syst, West Haven, CT USA. [Doll, Jennifer A.; Cornwell, Mona] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Pandol, Stephen J.] VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. RP Chung, CH (reprint author), Yale Univ, Sch Med, Dept Med, Sect Digest Dis, GI Res Bldg, West Haven, CT 06516 USA. EM chuhan.chung@yale.edu FU American Liver Foundation; NIH [DK34989, P60 AA11999, DK54021]; VA Merit Award FX The authors disclose the following: Supported by an American Liver Foundation grant; NIH Liver Center Core DK34989 (to C.C.), P60 AA11999 (to S.J.P.), DK54021; and VA Merit Award (to F.S.G.). NR 35 TC 23 Z9 25 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2009 VL 136 IS 1 BP 331 EP 340 DI 10.1053/j.gastro.2008.09.065 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 388OG UT WOS:000262028500041 PM 18996124 ER PT J AU Jou, J Radowsky, J Gangnon, R Sadowski, E Kays, S Hind, J Gaumnitz, E Taylor, A Robbins, J AF Jou, Janice Radowsky, Jason Gangnon, Ronald Sadowski, Elizabeth Kays, Stephanie Hind, Jacqueline Gaumnitz, Eric Taylor, Andrew Robbins, JoAnne TI Esophageal Clearance Patterns in Normal Older Adults as Documented with Videofluoroscopic Esophagram SO GASTROENTEROLOGY RESEARCH AND PRACTICE LA English DT Article ID HEALTHY-SUBJECTS; MANOMETRY; MOTILITY; AGE; VOLUNTEERS; IMPEDANCE; BARIUM AB Normal esophageal bolus transport in asymptomatic healthy older adults has not been well defined, potentially leading to ambiguity in differentiating esophageal swallowing patterns of dysphagic and healthy individuals. This pilot study of 24 young (4564 years) and old (65+years) men and women was designed to assess radiographic esophageal bolus movement patterns in healthy adults using videofluoroscopic recording. Healthy, asymptomatic adults underwent videofluoroscopic esophagram to evaluate for the presence of ineffective esophageal clearance, namely, intraesophageal stasis and intraesophageal reflux. Intraesophageal stasis and intraesophageal reflux were visualized radiographically in these normal subjects. Intraesophageal stasis occurred significantly more frequently with semisolid (96%) compared with liquid (16%) barium, suggesting that a variety of barium consistencies, as opposed to only the traditional fluids, would better define the spectrum of esophageal transport. Intraesophageal reflux was observed more frequently in older males than in their younger counterparts. The rates of intraesophageal stasis and intraesophageal reflux were potentially high given that successive bolus presentations were spaced 10 seconds apart. These findings suggest a need for a more comprehensive definition regarding the range of normal esophageal bolus transport to (a) prevent misdiagnosis of dysphagia and (b) to enhance generalization to functional eating, which involves solid foods in addition to liquids. Copyright (C) 2009 Janice Jou et al. C1 [Jou, Janice; Radowsky, Jason; Kays, Stephanie; Hind, Jacqueline; Gaumnitz, Eric; Robbins, JoAnne] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Sect Gastroenterol & Hepatol, Madison, WI 53792 USA. [Radowsky, Jason; Kays, Stephanie; Hind, Jacqueline; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, US Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. [Gangnon, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53792 USA. [Sadowski, Elizabeth; Taylor, Andrew] Univ Wisconsin, Sch Med & Pulic Hlth, Dept Radiol, Madison, WI 53792 USA. RP Robbins, J (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Sect Gastroenterol & Hepatol, Madison, WI 53792 USA. EM jrobbin2@wisc.edu FU Geriatric Research, Education and Clinical Center (GRECC); William S. Middleton Memorial VA Hospital FX This work supported by the Geriatric Research, Education and Clinical Center (GRECC), and William S. Middleton Memorial VA Hospital. The authors would like to thank Abby Duane, BS, for manuscript preparation and also extend their appreciation to the Department of Radiology University of Wisconsin. This is GRECC manuscript 2006-12. NR 24 TC 7 Z9 7 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-6121 J9 GASTROENT RES PRACT JI Gastroenterol. Res. Pract. PY 2009 AR 965062 DI 10.1155/2009/965062 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 689FJ UT WOS:000284912400001 ER PT J AU Shergill, AK Asundi, KR Barr, A Shah, JN Ryan, JC McQuaid, KR Rempel, D AF Shergill, Amandeep K. Asundi, Krishna R. Barr, Alan Shah, Janak N. Ryan, James C. McQuaid, Kenneth R. Rempel, David TI Pinch force and forearm-muscle load during routine colonoscopy: a pilot study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CUMULATIVE TRAUMA DISORDERS; OVERUSE AB Background and Objective: Overuse injuries of the hand, wrist, forearm, and shoulder are common among endoscopists and may be from repetitive pinching and gripping forces or awkward posturing. In this pilot study, we evaluated distal upper-extremity musculoskeletal load during colonoscopy (1) to confirm the feasibility of performing ergonomic measurements in endoscopists and (2) to identify tasks that may contribute to overuse injuries. Design and Subjects: Three experienced gastroenterologists were evaluated during 3 colonoscopies each Setting: Veterans Affairs Medical Center, San Francisco, California. Main Outcome Measurement: Right-thumb pinch force using a thumb-force sensor and bilateral forearm-muscle activity using electromyography. Results: The mean duration of the 9 colonoscopies was 19.5 minutes. The highest mean (SD) right-thumb peak pinch forces occurred during left (10.4 [4.1] N) and right (10.1 [4.5] N) colon insertion, which exceeded the injury threshold of 10 N. Mean peak forearm-muscle activity was also greatest during left and right colon insertion. Activity of the left abductor pollicis longus, left extensor carpi radialis, and right extensor carpi radialis exceeded the American Conference of industrial Hygienists (ACGIH) hand activity level (HAL) action limit. The left extensor carpi radialis was at the ACGIH HAL threshold limit. Limitations: The small sample size, no force measurement for the left thumb, and all the gastroenterologists were men. Conclusion: The pinch forces and forearm-muscle loads applied during routine colonoscopy may pose a risk for overuse injuries at the elbow and wrist. C1 [Shergill, Amandeep K.] Univ Calif San Francisco, Dept Med, Div Gastroenterol, VA Med Ctr, San Francisco, CA 94121 USA. [Shergill, Amandeep K.; Shah, Janak N.; Ryan, James C.; McQuaid, Kenneth R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Barr, Alan; Rempel, David] Univ Calif San Francisco, Dept Med, Div Occupat Med, San Francisco, CA 94121 USA. [Barr, Alan; Rempel, David] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Asundi, Krishna R.] Harvard Univ, Sch Med, Dept Environm Hlth, Boston, MA USA. RP Shergill, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Gastroenterol, VA Med Ctr, 4150 Clement St,Bldg 203,111B1, San Francisco, CA 94121 USA. EM amandeep.shergill@ucsf.edu RI Rempel, David/E-8424-2013 NR 10 TC 22 Z9 23 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2009 VL 69 IS 1 BP 142 EP 146 DI 10.1016/j.gie.2008.09.030 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 391VI UT WOS:000262261900023 PM 19111694 ER PT J AU Willingham, FF Gee, DW Sylla, P Lauwers, GY Rattner, DW Brugge, WR AF Willingham, Field F. Gee, Denise W. Sylla, Patricia Lauwers, Gregory Y. Rattner, David W. Brugge, William R. TI En bloc esophageal mucosectomy for concentric circumferential mucosal resection (with video) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ORIFICE TRANSESOPHAGEAL MEDIASTINOSCOPY; HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; INTRAMUCOSAL CARCINOMA; STRICTURE FORMATION; FOLLOW-UP; PREVENTION; EMR; THORACOSCOPY; REMOVAL AB Background: With conventional EMR, specimens are fragmented, metaplasia may be left behind, and invasive lesions could be missed because of incomplete sampling. Concentric subtotal esophageal mucosectomy would address these limitations. Objective: To examine en bloc esophageal mucosectomy (EEM). Design: A prospective case series. Setting: An academic hospital. Subjects: Nine swine. Interventions: Conventional EMR was performed in the proximal esophagus. The submucosal space was entered, and the distal two thirds of the esophageal mucosa was freed with blunt dissection. A snare was threaded over the Column of mucosa to the gastroesophageal junction. The column was resected, and the mucosa was retrieved. Main Outcome and Measurements: Clinical examination, follow-up endoscopy, necropsy, and gross and histopathologic examination. Results: EEM permitted Subtotal esophageal mucosectomy in 9 of 9 swine (tissue specimens removed ranged 9-15 cm in length). The mean procedure duration was 110 minutes. In the survival series, 4 of 4 swine thrived after Surgery, for 9 to 13 clays. At 9 clays, there was no evidence of a perforation, Stricture, or leak. At 13 clays, 2 swine had a mild proximal stricture, which was easily traversed with a 9.8-mm gastroscope. On necropsy, the mediastinal and thoracic cavities were unremarkable in 3 of 4 swine. One swine was found to have a contained abscess containing cellulose, presumably secondary to ingestion of wood-chip bedding material postoperatively Reepithelialization was present on histologic examination. Limitations: An animal study. Conclusions: EEM is feasible and enabled concentric subtotal esophageal mucosal resection. The technique I could completely and circumferentially excise intramucosal lesions. Longer follow-up and larger studies are I needed to evaluate infection, stricture, and safety. C1 [Willingham, Field F.; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Gee, Denise W.; Sylla, Patricia; Rattner, David W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Dept Surg, Boston, MA USA. [Lauwers, Gregory Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM Wbrugge@partners.org OI Willingham, Field/0000-0002-7071-3001 NR 15 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2009 VL 69 IS 1 BP 147 EP 151 DI 10.1016/j.gie.2008.09.010 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 391VI UT WOS:000262261900024 PM 19111695 ER PT J AU Nolan-Stevaux, O Lau, J Truitt, ML Chu, GC Hebrok, M Fernandez-Zapico, ME Hanahan, D AF Nolan-Stevaux, Olivier Lau, Janet Truitt, Morgan L. Chu, Gerald C. Hebrok, Matthias Fernandez-Zapico, Martin E. Hanahan, Douglas TI GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation SO GENES & DEVELOPMENT LA English DT Article DE Pancreatic ductal adenocarcinoma; PDAC; hedgehog; Gli; Smoothened; pancreatic cancer ID SIGNALING PATHWAYS; HEDGEHOG PATHWAY; CANCER; ADENOCARCINOMA; BIOLOGY; GROWTH; MOUSE; PROLIFERATION; TUMORIGENESIS; REQUIREMENT AB Pancreatic ductal adenocarcinoma (PDAC) is characterized by the deregulation of the hedgehog signaling pathway. The Sonic Hedgehog ligand (Shh), absent in the normal pancreas, is highly expressed in pancreatic tumors and is sufficient to induce neoplastic precursor lesions in mouse models. We investigated the mechanism of Shh signaling in PDAC carcinogenesis by genetically ablating the canonical bottleneck of hedgehog signaling, the transmembrane protein Smoothened (Smo), in the pancreatic epithelium of PDAC-susceptible mice. We report that multistage development of PDAC tumors is not affected by the deletion of Smo in the pancreas, demonstrating that autocrine Shh-Ptch-Smo signaling is not required in pancreatic ductal cells for PDAC progression. However, the expression of Gli target genes is maintained in Smo-negative ducts, implicating alternative means of regulating Gli transcription in the neoplastic ductal epithelium. In PDAC tumor cells, we find that Gli transcription is decoupled from upstream Shh-Ptch-Smo signaling and is regulated by TGF-beta and KRAS, and we show that Gli1 is required both for survival and for the KRAS-mediated transformed phenotype of cultured PDAC cancer cells. C1 [Nolan-Stevaux, Olivier; Truitt, Morgan L.; Hanahan, Douglas] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Nolan-Stevaux, Olivier; Lau, Janet; Truitt, Morgan L.; Hebrok, Matthias; Hanahan, Douglas] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Lau, Janet; Hebrok, Matthias] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Chu, Gerald C.] Dana Farber Canc Ctr, Dept Med Oncol, Boston, MA 02143 USA. [Fernandez-Zapico, Martin E.] Mayo Clin, Div Oncol Res, Schulze Ctr Novel Therapeut, Rochester, MN 55905 USA. [Hanahan, Douglas] Univ Calif San Francisco, Dept Biophys & Biochem, San Francisco, CA 94143 USA. RP Hanahan, D (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM dh@ucsf.edu FU NIH [DK6053301A1, CA112537-01]; PANCAN Career Development Award for Pancreatic Cancer Research [CA125127]; Mayo Clinic Pancreatic SPORE [P50 CA102701]; University of Iowa/Mayo Clinic Lymphoma SPORE [P50 CA097274]; Damon Runyon Cancer Research Foundation [DRG-1831-04] FX We are indebted to Drs. Ya-Jun Li and Pao-Tien Chuang for their gift of the anti-Smo antibody. We thank N. Bardeesy and R. DePinho for critical reading of the manuscript; members of the Hanahan and Hebrok laboratories for scientific discussions, in particular, P. Olson, J. Morris, and M. Pasca di Magliano; the Helen Diller Family Comprehensive Cancer Center Genome Analysis Core Facility for TaqMan analysis; and E. Drori, M. Vayner, S. Cacacho, and A. Wang for technical assistance. This work was supported by grants from the NIH to M. H. (DK6053301A1, CA112537-01), M. E. F. Z. (CA125127, Carole and Bob Daly AACR-PANCAN Career Development Award for Pancreatic Cancer Research, Mayo Clinic Pancreatic SPORE P50 CA102701, University of Iowa/Mayo Clinic Lymphoma SPORE P50 CA097274), and D. H. (program project grant on pancreatic cancer; R. DePinho, P. I.). O. N. S. was a Merck Fellow of the Damon Runyon Cancer Research Foundation (DRG-1831-04). NR 29 TC 210 Z9 219 U1 4 U2 11 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 JAN 1 PY 2009 VL 23 IS 1 BP 24 EP 36 DI 10.1101/gad.1753809 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 393JN UT WOS:000262369700004 PM 19136624 ER PT J AU Kahle, KT Wilson, FH Lifton, RP AF Kahle, Kristopher T. Wilson, Frederick H. Lifton, Richard P. BE Lifton, RP Somlo, S Giebisch, GH Seldin, DW TI The Syndrome of Hypertension and Hyperkalemia (Pseudohypoaldosteronism Type II): WNK Kinases Regulate the Balance Between Renal Salt Reabsorption and Potassium Secretion SO GENETIC DISEASES OF THE KIDNEY LA English DT Article; Book Chapter ID NA-CL COTRANSPORTER; PARACELLULAR CHLORIDE PERMEABILITY; EPITHELIAL SODIUM-CHANNEL; ALANINE-RICH KINASE; BLOOD-PRESSURE; FAMILIAL HYPERKALEMIA; MOLECULAR PATHOGENESIS; INHERITED HYPERTENSION; GENERAL-POPULATION; ALDOSTERONE LEVELS C1 [Kahle, Kristopher T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Wilson, Frederick H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. RP Kahle, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. NR 84 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092427-4 PY 2009 BP 313 EP 329 DI 10.1016/B978-0-12-449851-8.00019-X PG 17 WC Urology & Nephrology SC Urology & Nephrology GA BEO63 UT WOS:000317591300020 ER PT J AU Levin, JZ Berger, MF Adiconis, X Rogov, P Melnikov, A Fennell, T Nusbaum, C Garraway, LA Gnirke, A AF Levin, Joshua Z. Berger, Michael F. Adiconis, Xian Rogov, Peter Melnikov, Alexandre Fennell, Timothy Nusbaum, Chad Garraway, Levi A. Gnirke, Andreas TI Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts SO GENOME BIOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL-LINE; MULTIPLEX AMPLIFICATION; GENE FUSIONS; EXON CAPTURE; RNA-SEQ; GENOME; SELECTION; IDENTIFICATION; REARRANGEMENTS AB Targeted RNA-Seq combines next-generation sequencing with capture of sequences from a relevant subset of a transcriptome. When testing by capturing sequences from a tumor cDNA library by hybridization to oligonucleotide probes specific for 467 cancer-related genes, this method showed high selectivity, improved mutation detection enabling discovery of novel chimeric transcripts, and provided RNA expression data. Thus, targeted RNA-Seq produces an enhanced view of the molecular state of a set of "high interest" genes. C1 [Levin, Joshua Z.; Adiconis, Xian; Rogov, Peter; Melnikov, Alexandre; Nusbaum, Chad; Gnirke, Andreas] Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, Cambridge, MA 02141 USA. [Berger, Michael F.; Garraway, Levi A.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA. [Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. RP Levin, JZ (reprint author), Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, 320 Charles St, Cambridge, MA 02141 USA. EM jlevin@broadinstitute.org FU National Human Genome Research Institute [HG03067-05]; Starr Cancer Consortium; National Institutes of Health [DP2OD002750] FX We thank the staff of the Broad Institute Genome Sequencing Platform for generating sequencing data. We are grateful for help from Terrance Shea and Sarah Young with SNP calling. This work was supported by National Human Genome Research Institute grant HG03067-05, the Starr Cancer Consortium (L.A.G.), and National Institutes of Health grant DP2OD002750 (LAG). NR 35 TC 92 Z9 93 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2009 VL 10 IS 10 AR R115 DI 10.1186/gb-2009-10-10-r115 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 525OY UT WOS:000272227000017 PM 19835606 ER PT J AU Xia, XB Kung, AL AF Xia, Xiaobo Kung, Andrew L. TI Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION; HUMAN GENOME; DNA-BINDING; HISTONE MODIFICATIONS; CPG METHYLATION; HIF-2-ALPHA; PROMOTERS; ASSOCIATION; HIF-1-ALPHA; CARCINOMA AB Background: Hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia. To better understand the determinants of HIF-1 binding and transactivation, we used ChIP-chip and gene expression profiling to define the relationship between the epigenetic landscape, sites of HIF-1 binding, and genes transactivated by hypoxia in two cell lines. Results: We found that when cells were acutely subjected to hypoxia, HIF-1 preferentially bound to loci that were already transcriptionally active under normal growth conditions characterized by the presence of histone H3 lysine 4 methylation, the presence of RNA polymerase II, and basal production of mRNA. Cell type-specific differences in HIF-1 binding were largely attributable to differences in the basal gene expression patterns in the cells prior to the onset of hypoxia. Conclusions: These results suggest that the repertoire of genes active in a cell (for example, through lineage specific transcription factors) defines the subset of genes that are permissive for binding and transactivation by stimulus-responsive transcription factors. C1 [Kung, Andrew L.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kung, AL (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM andrew_kung@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU American Cancer Society; National Institutes of Health (ALK) FX This work was supported by the American Cancer Society and the National Institutes of Health (ALK). NR 36 TC 42 Z9 42 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2009 VL 10 IS 10 AR R113 DI 10.1186/gb-2009-10-10-r113 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 525OY UT WOS:000272227000015 PM 19828020 ER PT J AU Gusella, JF MacDonald, ME AF Gusella, James F. MacDonald, Marcy E. TI Huntington's disease: the case for genetic modifiers SO GENOME MEDICINE LA English DT Review AB For almost three decades, Huntington's disease has been a prototype for the application of genetic strategies to human disease. HD, the Huntington's disease gene, was the first autosomal defect mapped using only DNA markers, a finding in 1983 that helped to spur similar studies in many other disorders and contributed to the concept of the human genome project. The search for the genetic defect itself pioneered many mapping and gene-finding technologies, and culminated in the identification of the HD gene, its mutation and its novel protein product in 1993. Since that time, extensive investigations into the pathogenic mechanism have utilized the knowledge of the disease gene and its defect but, with notable exceptions, have rarely relied for guidance on the genetic findings in human patients to interpret the relevance of findings in non-human model systems. However, the human patient still has much to teach us through a detailed analysis of genotype and phenotype. Such studies have implicated the existence of genetic modifiers - genes whose natural polymorphic variation contributes to altering the development of Huntington's disease symptoms. The search for these modifiers, much as the search for the HD gene did in the past, offers to open new entrees into the process of Huntington's disease pathogenesis by unlocking the biochemical changes that occur many years before diagnosis, and thereby providing validated target proteins and pathways for development of rational therapeutic interventions. C1 [Gusella, James F.; MacDonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu FU NIH NINDS [NS32765, NS16367]; Huntington's Disease Society of America Coalition for the Cure; CHDI Foundation, Inc. FX The authors' work on Huntington's disease is supported by NIH NINDS grants NS32765 and NS16367, the Huntington's Disease Society of America Coalition for the Cure, an anonymous donor and the CHDI Foundation, Inc. NR 55 TC 47 Z9 48 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 80 DI 10.1186/gm80 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000080 PM 19725930 ER PT J AU Kaelin, WG AF Kaelin, William G., Jr. TI Synthetic lethality: a framework for the development of wiser cancer therapeutics SO GENOME MEDICINE LA English DT Review AB The challenge in medical oncology has always been to identify compounds that will kill, or at least tame, cancer cells while leaving normal cells unscathed. Most chemotherapeutic agents in use today were selected primarily for their ability to kill rapidly dividing cancer cells grown in cell culture and in mice, with their selectivity determined empirically during subsequent animal and human testing. Unfortunately, most of the drugs developed in this way have relatively low therapeutic indices (low toxic dose relative to the therapeutic dose). Recent advances in genomics are leading to a more complete picture of the range of mutations, both driver and passenger, present in human cancers. Synthetic lethality provides a conceptual framework for using this information to arrive at drugs that will preferentially kill cancer cells relative to normal cells. It also provides a possible way to tackle 'undruggable' targets. Two genes are synthetically lethal if mutation of either gene alone is compatible with viability but simultaneous mutation of both genes leads to death. If one is a cancer-relevant gene, the task is to discover its synthetic lethal interactors, because targeting these would theoretically kill cancer cells mutant in the cancer-relevant gene while sparing cells with a normal copy of that gene. All cancer drugs in use today, including conventional cytotoxic agents and newer 'targeted' agents, target molecules that are present in both normal cells and cancer cells. Their therapeutic indices almost certainly relate to synthetic lethal interactions, even if those interactions are often poorly understood. Recent technical advances enable unbiased screens for synthetic lethal interactors to be undertaken in human cancer cells. These approaches will hopefully facilitate the discovery of safer, more efficacious anticancer drugs that exploit vulnerabilities that are unique to cancer cells by virtue of the mutations they have accrued during tumor progression. C1 [Kaelin, William G., Jr.] Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 54 TC 45 Z9 45 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 99 DI 10.1186/gm99 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000099 PM 19863774 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: Crohn's disease SO GENOME MEDICINE LA English DT Editorial Material AB The inflammatory bowel diseases, Crohn's disease and ulcerative colitis, pose a fascinating challenge to specialists in gastroenterology, infectious diseases, immunology and genetics and an often crushing burden to patients and their families. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 103 DI 10.1186/gm103 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000103 PM 19891793 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: enzyme-replacement therapy of the lysosomal storage diseases SO GENOME MEDICINE LA English DT Editorial Material AB The lysosomal storage diseases, such as Gaucher's disease, mucopolysaccharidosis I, II and IV, Fabry's disease, and Pompe's disease, are rare inherited disorders whose symptoms result from enzyme deficiency causing lysosomal accumulation. Until effective gene-replacement therapy is developed, expensive, and at best incomplete, enzyme-replacement therapy is the only hope for sufferers of rare lysosomal storage diseases. Preventive strategies involving carrier detection should be a priority toward the successful management of these conditions. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 29 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 114 DI 10.1186/gm114 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000114 PM 20017892 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: the Obama effect SO GENOME MEDICINE LA English DT Editorial Material AB The inauguration of the Obama administration is likely to enhance the role of genome medicine in clinical care and national economics. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 30 DI 10.1186/gm30 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000030 PM 19341501 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: abuse of genetic tests SO GENOME MEDICINE LA English DT Editorial Material AB The wide general publication of a putative genetic test for athletic supremacy is clearly an abuse of genetics and reveals an undercurrent of hucksterism in biomedical science. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 18 DI 10.1186/gm18 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000018 PM 19341489 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: the slow but inexorable process of medical care reform in the United States SO GENOME MEDICINE LA English DT Editorial Material AB The current healthcare system in the United States is unsustainable, but any attempts at improvement must be carefully managed to avoid weakening the country's contribution to biomedical science research and the future of genome medicine. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 94 DI 10.1186/gm94 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000094 PM 19822025 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: the Obama effect redux SO GENOME MEDICINE LA English DT Editorial Material AB From the point of view of genome medicine, Barack Obama has made two vital policy decisions: he has chosen a new director of the National Institutes of Health, and his proposed change in United States healthcare policy will have profound effects on genome medicine and, indeed, all of academic medicine. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 86 DI 10.1186/gm86 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000086 PM 19769781 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: cholesterol and coronary artery disease SO GENOME MEDICINE LA English DT Article AB Cholesterol levels and not inflammatory markers are the major variables that pose a risk of coronary artery disease. Diabetes greatly increases the risk at any cholesterol level. Coronary artery disease and cancer are linked by a common protein - an apoptotic protein that also functions as a regulator of insulin secretion. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 60 DI 10.1186/gm60 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000060 PM 19519958 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: cancer genetics and the promise of effective treatment SO GENOME MEDICINE LA English DT Editorial Material AB Cancer is the most common acquired genetic disease. Great progress has been made in documenting the genetic abnormalities that cause the disease, and in the future each tumor will be subjected to genetic analysis and the appropriate combination of drugs selected. Although there are serious technological and cost hurdles to surmount and resistance and continued mutation will be a constant problem, the way is clear to rational therapy. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 37 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 49 DI 10.1186/gm49 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000049 PM 19439059 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: gene therapy SO GENOME MEDICINE LA English DT Editorial Material AB Though the field has moved with glacial speed, gene therapies have been carried out successfully in patients with bone marrow disorders including immune deficiencies. The field may be poised to move forward more rapidly, but many barriers have yet to be surmounted. C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 29 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 38 DI 10.1186/gm38 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000038 PM 19435468 ER PT J AU Nathan, DG Orkin, SH AF Nathan, David G. Orkin, Stuart H. TI Musings on genome medicine: genome wide association studies SO GENOME MEDICINE LA English DT Editorial Material C1 [Nathan, David G.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 16 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 3 DI 10.1186/gm3 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000003 PM 19348690 ER PT J AU Quackenbush, J AF Quackenbush, John TI Data reporting standards: making the things we use better SO GENOME MEDICINE LA English DT Article AB Genomic data often persist far beyond the initial study in which they were generated. But the true value of the data is tied to their being both used and useful, and the usefulness of the data relies intimately on how well annotated they are. While standards such as MIAME have been in existence for nearly a decade, we cannot think that the problem is solved or that we can ignore the need to develop better, more effective methods for capturing the essence of the meta-data that is ultimately required to guarantee utility of the data. C1 [Quackenbush, John] Dana Farber Canc Inst, Dept Biostatis & Computat Biol, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, Dept Biostatis & Computat Biol, 44 Binney St,Sm822, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu NR 9 TC 9 Z9 9 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 111 DI 10.1186/gm111 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000111 PM 19939294 ER PT J AU Udayakumar, D Tsao, H AF Udayakumar, Durga Tsao, Hensin TI Moderate- to low-risk variant alleles of cutaneous malignancies and nevi: lessons from genome-wide association studies SO GENOME MEDICINE LA English DT Review AB Cutaneous malignancies, especially malignant melanoma, exhibit great genetic heterogeneity. As a result, some individuals and families have particularly increased risk due to genetic predisposition to the disease. The susceptibility alleles range from rarely occurring, heritable, high-risk variants to ubiquitously occurring low-risk variants. Although until now the focus has been mostly towards the familial high-risk genes, the development of genome-wide association studies has uncovered a number of moderate-to low-risk predisposition alleles. The ability to specifically identify genetic variation associated with visible pigmentation traits and disease risk has provided a much richer view of the genetics of cutaneous malignancies. In this review, we provide an update on the recently identified risk loci. Existing clinical data, combined with vast genome information, will provide a better understanding of the biology of disease, and increased accuracy in risk prediction. C1 [Udayakumar, Durga; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Udayakumar, Durga; Tsao, Hensin] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tsao, Hensin] MGH Canc Ctr, MGH Melanoma & Pigmented Les Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, 48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 36 TC 7 Z9 7 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2009 VL 1 AR 95 DI 10.1186/gm95 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA V27QF UT WOS:000208627000095 PM 19863770 ER PT J AU Yee, AJ Ramaswamy, S AF Yee, Andrew J. Ramaswamy, Sridhar BE Willard, HF Ginsburg, GS TI DNA Microarrays in Biological Discovery and Patient Care SO GENOMIC AND PERSONALIZED MEDICINE, VOL 1 LA English DT Article; Book Chapter ID PARAFFIN-EMBEDDED TISSUES; POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION PATTERNS; B-CELL LYMPHOMA; BREAST-CANCER PROGRESSION; OLIGONUCLEOTIDE ARRAYS; MESSENGER-RNA; CDNA MICROARRAYS; MOLECULAR CLASSIFICATION; FUNCTIONAL GENOMICS C1 [Yee, Andrew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. [Ramaswamy, Sridhar] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yee, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. NR 124 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-370888-5 PY 2009 BP 157 EP 172 DI 10.1016/B978-0-12-369420-1.00013-5 PG 16 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA BCX27 UT WOS:000311822400015 ER PT J AU Weissleder, R AF Weissleder, Ralph BE Willard, HF Ginsburg, GS TI Molecular Imaging as a Paradigm for Genomic and Personalized Medicine SO GENOMIC AND PERSONALIZED MEDICINE, VOL 1 LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; ONCOLOGY DRUG DEVELOPMENT; IN-VIVO; PLAQUE INFLAMMATION; LUNG-CANCER; END-POINTS; BREAST; PET; DISCOVERY; ARTHRITIS C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 47 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-370888-5 PY 2009 BP 494 EP 499 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA BCX27 UT WOS:000311822400045 ER PT J AU Kathiresan, S Rader, DJ AF Kathiresan, Sekar Rader, Daniel J. BE Willard, HF Ginsburg, GS TI Lipoprotein Disorders SO GENOMIC AND PERSONALIZED MEDICINE, VOL 2 LA English DT Article; Book Chapter ID HIGH-DENSITY-LIPOPROTEIN; FAMILIAL COMBINED HYPERLIPIDEMIA; GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; APOLIPOPROTEIN-A-I; TRIGLYCERIDE TRANSFER PROTEIN; UPSTREAM TRANSCRIPTION FACTOR-1; CASSETTE TRANSPORTER 1; HEART-DISEASE; TANGIER-DISEASE C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Boston, MA 02114 USA. [Rader, Daniel J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Boston, MA 02114 USA. NR 103 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-370889-2 PY 2009 BP 634 EP 651 DI 10.1016/B978-0-12-369420-1.00055-X PG 18 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA BCU33 UT WOS:000311433700004 ER PT J AU Febbo, PG Kantoff, PW AF Febbo, Phillip G. Kantoff, Philip W. BE Willard, HF Ginsburg, GS TI Prostate Cancer SO GENOMIC AND PERSONALIZED MEDICINE, VOL 2 LA English DT Article; Book Chapter ID CIRCULATING TUMOR-CELLS; GENE-EXPRESSION PROFILES; GENOME-WIDE ASSOCIATION; ANDROGEN-RECEPTOR GENE; COENZYME-A RACEMASE; RADICAL PROSTATECTOMY; THERAPEUTIC IMPLICATIONS; EPIGENETIC INACTIVATION; MICROARRAY ANALYSIS; MAGNETIC-RESONANCE C1 [Febbo, Phillip G.] Duke Univ, Med Ctr, Dept Med Oncol, Inst Genome Sci & Policy, Durham, NC 27710 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Febbo, PG (reprint author), Duke Univ, Med Ctr, Dept Med Oncol, Inst Genome Sci & Policy, Durham, NC 27710 USA. NR 130 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-370889-2 PY 2009 BP 898 EP 912 DI 10.1016/B978-0-12-369420-1.00074-3 PG 15 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA BCU33 UT WOS:000311433700023 ER PT J AU Wiggs, JL AF Wiggs, Janey L. BE Willard, HF Ginsburg, GS TI Ophthalmology SO GENOMIC AND PERSONALIZED MEDICINE, VOL 2 LA English DT Article; Book Chapter ID COMPLEMENT FACTOR-H; GRANULAR CORNEAL-DYSTROPHY; OPEN-ANGLE GLAUCOMA; DOMINANT RETINITIS-PIGMENTOSA; NUCLEAR PULVERULENT CATARACT; B-CRYSTALLIN MUTATION; DNA-SEQUENCE VARIANTS; GROENOUW TYPE-I; MACULAR DEGENERATION; MOLECULAR-GENETICS C1 [Wiggs, Janey L.] Harvard Univ, Sch Med, Dept Opthalmol, Boston, MA 02114 USA. [Wiggs, Janey L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Dept Opthalmol, Boston, MA 02114 USA. NR 81 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-370889-2 PY 2009 BP 1256 EP 1264 DI 10.1016/B978-0-12-369420-1.00102-5 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA BCU33 UT WOS:000311433700051 ER PT S AU Yehuda, R AF Yehuda, Rachel BE Judd, LL Sternberg, EM TI Status of Glucocorticoid Alterations in Post-traumatic Stress Disorder SO GLUCOCORTICOIDS AND MOOD CLINICAL MANIFESTATIONS, RISK FACTORS, AND MOLECULAR MECHANISMS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Glucocorticoids and Mood - Clinical Manifestations, Risk Factors and Molecular Mechanisms CY JUN 20-21, 2008 CL San Diego, CA DE acth; cortisol; depression; dexamethasone; glucocorticoid receptors ID PITUITARY-ADRENAL AXIS; DEXAMETHASONE-SUPPRESSION TEST; URINARY CORTISOL-LEVELS; BORDERLINE PERSONALITY-DISORDER; CORTICOTROPIN-RELEASING-FACTOR; MAJOR DEPRESSIVE DISORDER; VEHICLE ACCIDENT VICTIMS; HORMONE STIMULATION TEST; CIVILIAN TRAUMA VICTIMS; CHILDHOOD SEXUAL ABUSE AB The current status of glucocorticoid alterations in post-traumatic stress disorder (PTSD) will be described in this chapter. Emphasis will be placed on data that suggest that at least some glucocorticoid-related observations in PTSD reflect pretraumatic glucocorticoid status. Recent observations have provided some evidence that pretraumatic glucocorticoid alterations may arise from genetic, epigenetic, and possibly other environmental influences that serve to increase the likelihood of developing PTSD following trauma exposure, as well as modulate attendant biological alterations associated with its pathophysiology. Current studies in the field of PTSD employ glucocorticoid challenge strategies to delineate effects of exogenously administered glucocorticoids on neuroendocrine, cognitive, and brain function. Results of these studies have provided an important rationale for using glucocorticoid strategies in the treatment of PTSD. C1 [Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, New York, NY USA. [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, PTSD Program, Bronx, NY USA. RP Yehuda, R (reprint author), Bronx VA, OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov FU NIH [R01 N4H064675-02, R01 MH64104-01]; VA Merit Funds; DOD funds FX This work was Supported by NIH: R01 N4H064675-02, R01 MH64104-01. VA Merit Funds, and DOD funds. The author wishes to acknowledge Janelle Wolaltmann, Casey Sarapas, Chuck Burton, and Michelle Pelcovitz for assisting in the preparation of this manuscript. NR 140 TC 162 Z9 171 U1 2 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-748-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1179 BP 56 EP 69 DI 10.1111/j.1749-6632.2009.04979.x PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMJ24 UT WOS:000272551200004 PM 19906232 ER PT J AU Kokkotou, E Espinoza, DO Torres, D Karagiannides, I Kosteletos, S Savidge, T O'Brien, M Pothoulakis, C AF Kokkotou, E. Espinoza, D. O. Torres, D. Karagiannides, I. Kosteletos, S. Savidge, T. O'Brien, M. Pothoulakis, C. TI Melanin-concentrating hormone (MCH) modulates C difficile toxin A-mediated enteritis in mice SO GUT LA English DT Article ID STIMULATED INTERLEUKIN-8 EXPRESSION; COLONIC EPITHELIAL-CELLS; ENDOPEPTIDASE EC 3.4.24.11; DORSAL-ROOT GANGLIA; SUBSTANCE-P; INTESTINAL INFLAMMATION; NEUTRAL ENDOPEPTIDASE; SIGNALING PATHWAYS; UP-REGULATION; RECEPTOR AB Objective: Melanin-concentrating hormone (MCH) is a hypothalamic orexigenic neuropeptide that regulates energy balance. However, the distribution of MCH and its receptor MCHR1 in tissues other than brain suggested additional, as yet unappreciated, roles for this neuropeptide. Based on previous paradigms and the presence of MCH in the intestine as well as in immune cells, its potential role in gut innate immune responses was examined. Methods: In human intestinal xenografts grown in mice, changes in the expression of MCH and its receptors following treatment with Clostridium difficile toxin A, the causative agent of antibiotic-associated diarrhoea in hospitalised patients, were examined. In colonocytes, the effect of C difficile toxin A treatment on MCHR1 expression, and of MCH on interleukin 8 (IL8) expression was examined. MCH-deficient mice and immunoneutralisation approaches were used to examine the role of MCH in the pathogenesis of C difficile toxin A-mediated acute enteritis. Results: Upregulation of MCH and MCHR1 expression was found in the human intestinal xenograft model, and of MCHR1 in colonocytes following exposure to toxin A. Treatment of colonocytes with MCH resulted in IL8 transcriptional upregulation, implying a link between MCH and inflammatory pathways. In further support of this view, MCH-deficient mice developed attenuated toxin A-mediated intestinal inflammation and secretion, as did wild-type mice treated with an antibody against MCH or MCHR1. Conclusion: These findings signify MCH as a mediator of C difficile-associated enteritis and possibly of additional gut pathogens. MCH may mediate its proinflammatory effects at least in part by acting on epithelial cells in the intestine. C1 [Kokkotou, E.; Espinoza, D. O.; Torres, D.; Karagiannides, I.; Kosteletos, S.; Pothoulakis, C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Boston, MA 02215 USA. [Kokkotou, E.; Savidge, T.; Pothoulakis, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Boston, MA 02215 USA. [O'Brien, M.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. RP Kokkotou, E (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, 330 Brookline Ave, Boston, MA 02215 USA. EM ekokkoto@bidmc.harvard.edu OI O'Brien, Michael J/0000-0003-1124-3537 FU National Institutes of Health [DK080058, DK 033506]; Broad Medical Research Program of The Broad Foundation [IBD-0165]; Harvard Clinical Nutrition Research Center [P30-DK040561]; American Gastroenterological Association Foundation (AGA Foundation) Bridging Grant (EK) FX We thank Dr Eleftheria Maratos-Flier for providing us with MCH knockout breeding pairs. This work was supported by research grants DK080058 (EK) and DK 033506 (CP, TS) from the National Institutes of Health, IBD-0165 from the Broad Medical Research Program of The Broad Foundation (EK), P30-DK040561 from the Harvard Clinical Nutrition Research Center (EK) and by an American Gastroenterological Association Foundation (AGA Foundation) Bridging Grant (EK). NR 56 TC 19 Z9 19 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JAN PY 2009 VL 58 IS 1 BP 34 EP 40 DI 10.1136/gut.2008.155341 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 385DU UT WOS:000261794200009 PM 18824554 ER PT J AU Ogino, S Nosho, K Kirkner, GJ Kawasaki, T Meyerhardt, JA Loda, M Giovannucci, EL Fuchs, CS AF Ogino, Shuji Nosho, Katsuhiko Kirkner, Gregory J. Kawasaki, Takako Meyerhardt, Jeffrey A. Loda, Massimo Giovannucci, Edward L. Fuchs, Charles S. TI CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer SO GUT LA English DT Article ID SPORADIC COLORECTAL-CANCER; POPULATION-BASED SAMPLE; LOW CIMP-LOW; DNA METHYLATION; CHROMOSOMAL INSTABILITY; SURVIVAL; ASSOCIATION; EXPRESSION; PROGNOSIS; KRAS AB Background: The CpG island methylator phenotype (CIMP), characterised by widespread promoter methylation, is associated with microsatellite instability (MSI) and BRAF mutation in colorectal cancer. The independent effect of CIMP, MSI and BRAF mutation on prognosis remains uncertain. Methods: Utilising 649 colon cancers (stage I-IV) in two independent cohort studies, we quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) as well as CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN by using MethyLight technology. We examined MSI, KRAS and BRAF status. Cox proportional hazard models computed hazard ratios (HRs) for colon cancer-specific and overall mortalities, adjusting for patient characteristics and tumoral molecular features. Results: After adjustment for other predictors of patient survival, patients with CIMP-high cancers (126 (19%) tumours with >= 6/8 methylated CIMP-specific promoters) experienced a significantly low colon cancer-specific mortality (multivariate HR 0.44, 95% confidence interval (CI) 0.22 to 0.88), whereas the BRAF mutation was significantly associated with a high cancer-specific mortality (multivariate HR 1.97, 95% CI 1.13 to 3.42). A trend toward a low cancer-specific mortality was observed for MSI-high tumours (multivariate HR 0.70, 95% CI 0.36 to 1.37). In stratified analyses, CIMP-high tumours were associated with a significant reduction in colon cancer-specific mortality, regardless of both MSI and BRAF status. The relation between CIMP-high and lower mortality appeared to be consistent across all stages. KRAS mutation was unrelated to prognostic significance. Conclusion: CIMP-high appears to be an independent predictor of a low colon cancer-specific mortality, while BRAF mutation is associated with a high colon cancer-specific mortality. C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ogino, Shuji; Nosho, Katsuhiko; Kawasaki, Takako; Meyerhardt, Jeffrey A.; Loda, Massimo; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU U.S. National Institute of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Targeted Therapies Research; Entertainment Industry Foundation National Colorectal Cancer Research Alliance; Japan Society for the Promotion of Science FX This work was supported by The U.S. National Institute of Health grants P01 CA87969, P01 CA55075, P50 CA127003, and K07 CA122826 (to SO), the Bennett Family Fund for Targeted Therapies Research, and the Entertainment Industry Foundation National Colorectal Cancer Research Alliance. KN was supported by a fellowship grant from the Japan Society for the Promotion of Science. NR 49 TC 402 Z9 406 U1 2 U2 30 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JAN PY 2009 VL 58 IS 1 BP 90 EP 96 DI 10.1136/gut.2008.155473 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 385DU UT WOS:000261794200018 PM 18832519 ER PT J AU Moore, RG McMeekin, DS Brown, AK DiSilvestro, P Miller, MC Allard, WJ Gajewski, W Kurman, R Bast, RC Skates, SJ AF Moore, Richard G. McMeekin, D. Scott Brown, Amy K. DiSilvestro, Paul Miller, M. Craig Allard, W. Jeffrey Gajewski, Walter Kurman, Robert Bast, Robert C., Jr. Skates, Steven J. TI A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Tumor marker; Pelvic mass; CA125; HE4; Ovarian cancer; Ovarian cancer detection ID MALIGNANCY INDEX; SURVIVAL; CARCINOMA; CA-125; MANAGEMENT; SURGERY; PROTEIN; IMPACT; RISK; CARE AB Introduction. Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass. Methods. Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC. Results. Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI = 85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI = 68.2-80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI = 58.8-89.3). Conclusion. An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence. (c) 2008 Elsevier Inc. All rights reserved. C1 [Moore, Richard G.; DiSilvestro, Paul] Brown Univ, Women & Infants Hosp, Program Womens Oncol, Providence, RI 02925 USA. [McMeekin, D. Scott] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Brown, Amy K.] Hartford Hosp, Hartford, CT 06115 USA. [Miller, M. Craig; Allard, W. Jeffrey] Fujirebio Diagnost Inc, Malvern, PA USA. [Gajewski, Walter] Coastal Hlth, Wilmington, NC USA. [Kurman, Robert] Johns Hopkins Med Sch, Baltimore, MD USA. [Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Skates, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Moore, RG (reprint author), Brown Univ, Women & Infants Hosp, Program Womens Oncol, Providence, RI 02925 USA. EM rmoore@wihri.org RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU Fujirebio Diagnostics Inc.; NCI [CA086381, CA105009] FX This study was supported by Fujirebio Diagnostics Inc. and by NCI grants CA086381 and CA105009 (S. Skates). NR 23 TC 291 Z9 316 U1 6 U2 31 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2009 VL 112 IS 1 BP 40 EP 46 DI 10.1016/j.ygyno.2008.08.031 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 396JN UT WOS:000262588100009 PM 18851871 ER PT J AU Hess, CJ Feller, N Denkers, F Kelder, A Merle, PA Heinrich, MC Harlow, A Berkhof, J Ossenkoppele, GJ Waisfisz, Q Schuurhuis, GJ AF Hess, Corine J. Feller, Nicole Denkers, Fedor Kelder, Angele Merle, Pauline A. Heinrich, Michael C. Harlow, Amy Berkhof, Johannes Ossenkoppele, Gert J. Waisfisz, Quinten Schuurhuis, Gerrit J. TI Correlation of minimal residual disease cell frequency with molecular genotype in patients with acute myeloid leukemia SO Haematologica-The Hematology Journal LA English DT Article DE acute myeloid leukemia; minimal residual disease; FLT3 ID RESISTANCE PROTEIN-ACTIVITY; P-GLYCOPROTEIN; FLOW-CYTOMETRY; MUTATIONS; AML; DIAGNOSIS; THERAPY; SURVIVAL; RELAPSE AB Background About 70-80 percent of patients with acute myeloid leukemia enter complete remission, but at least half of these patients who achieve remission go on to relapse. Improved treatment is likely to come from increasing the time to relapse, especially for younger patients. With the vastly increasing number of targeted therapies there is a strong need for short-term end-points to efficiently test such therapies for further pursuance. Minimal residual disease assessment may offer such an end-point since it is a strong independent prognostic factor. As proof of principle we examined this concept for FLT3-ITD status at diagnosis. Design and Methods We determined FLT3-ITD status in bone marrow samples from 196 patients with newly diagnosed acute myeloid leukemia. The frequencies of residual leukemic cells of these 196 patients were assessed in 267 follow-up bone marrow samples using immunophenotypic assessment of minimal residual disease. Results The median frequency of residual leukemic cells after the first cycle of chemotherapy was 8.5-fold higher in patients with FLT3-ITD than in those with wild type FLT3. Such a difference translates into differences in survival, even if other potentially outcome-modulating mutations, such as NPM1, KIT, NRAS, KRAS, FLT3-exon 20 and PTPN11 are included in the analysis. Conclusions This study shows that it could be possible to study the efficacy of FLT3 inhibitors using the level of minimal residual disease as a short-term end-point. C1 [Schuurhuis, Gerrit J.] Vrije Univ Amsterdam, Med Ctr, Dept Hematol, BR248, NL-1081 HV Amsterdam, Netherlands. [Heinrich, Michael C.; Harlow, Amy] Oregon Hlth & Sci Univ, Inst Canc, Dept Pathol & Med, Portland, OR 97201 USA. [Heinrich, Michael C.; Harlow, Amy] Portland VA Med Ctr, Portland, OR USA. [Berkhof, Johannes] Vrije Univ Amsterdam, Med Ctr, Dept Clin Epidemiol & Biostat, NL-1081 HV Amsterdam, Netherlands. RP Schuurhuis, GJ (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Hematol, BR248, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM gj.schuurhuis@vumc.nl FU Leukemia and Lymphoma Society; VA merit Review Grant FX Funding: this manuscript was supported in part by funding from the Leukemia and Lymphoma Society (MCH) and a VA merit Review Grant (MCH). NR 20 TC 6 Z9 6 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2009 VL 94 IS 1 BP 46 EP 53 DI 10.3324/haematol.13110 PG 8 WC Hematology SC Hematology GA 396LL UT WOS:000262593100009 PM 19042917 ER PT J AU Verhaak, RGW Wouters, BJ Erpelinck, CAJ Abbas, S Beverloo, HB Lugthart, S Lowenberg, B Delwel, R Valk, PJM AF Verhaak, Roel G. W. Wouters, Bas J. Erpelinck, Claudia A. J. Abbas, Saman Beverloo, H. Berna Lugthart, Sanne Lowenberg, Bob Delwel, Ruud Valk, Peter J. M. TI Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling SO Haematologica-The Hematology Journal LA English DT Article DE acute myeloid leukemia; gene expression profiling; prediction ID ACUTE MYELOGENOUS LEUKEMIA; NORMAL KARYOTYPE; CYTOPLASMIC NUCLEOPHOSMIN; FAVORABLE PROGNOSIS; NORMAL CYTOGENETICS; MUTATIONS; DISTINCT; ABNORMALITIES; SUBCLASSES; DIAGNOSIS AB We examined the gene expression profiles of two independent cohorts of patients with acute myeloid leukemia [n=247 and n=214 (younger than or equal to 60 years)] to study the applicability of gene expression profiling as a single assay in prediction of acute myeloid leukemia-specific molecular subtypes. The favorable cytogenetic acute myeloid leukemia subtypes, i.e., acute myeloid leukemia with t(8;21), t(15.17) or inv(16), were predicted with maximum accuracy (positive and negative predictive value: 100%). Mutations in NPM1 and CEBPA were predicted less accurately (positive predictive value: 66% and 100%, and negative predictive value: 99% and 97% respectively). Various other characteristic molecular acute myeloid leukemia subtypes, i.e., mutant FLT3 and RAS, abnormalities involving 11q23, -5/5q-, -7/7q-, abnormalities involving 3q (abn3q) and t(9-22), could not be correctly predicted using gene expression profiling. In conclusion, gene expression profiling allows accurate prediction of certain acute myeloid leukemia subtypes, e.g. those characterized by expression of chimeric transcription factors. However, detection of mutations affecting signaling molecules and numerical abnormalities still requires alternative molecular methods. C1 [Verhaak, Roel G. W.; Wouters, Bas J.; Erpelinck, Claudia A. J.; Abbas, Saman; Lugthart, Sanne; Lowenberg, Bob; Delwel, Ruud; Valk, Peter J. M.] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Verhaak, Roel G. W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Verhaak, Roel G. W.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Verhaak, Roel G. W.] Harvard Univ, Cambridge, MA 02138 USA. [Beverloo, H. Berna] Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3000 DR Rotterdam, Netherlands. RP Valk, PJM (reprint author), Erasmus Univ, Med Ctr Rotterdam, Dept Hematol, Ee1391a,Dr Molewaterpl 50, NL-3015 GE Rotterdam Zh, Netherlands. EM p.valk@erasmusmc.nl RI Abbas, Saman/L-1981-2013 FU Dutch Cancer Society; Erasmus University Medical Center FX this work was supported by grants from the Dutch Cancer Society (Koningin Wilhelmina Fonds) and the Erasmus University Medical Center (Revolving Fund). We are indebted to Gert J. Ossenkoppele, M.D. (Free University Medical Center, Amsterdam, The Netherlands), Jaap Jan Zwaginga M.D. (Sanquin, The Netherlands), Edo Vellenga, M.D. (University Hospital, Groningen, The Netherlands), Leo F Verdonck, M.D. (University Hospital, Utrecht, The Netherlands), Gregor Verhoef, M.D. (Hospital Gasthuisberg, Leuven, Belgium) and Matthias Theobald, M.D. (Johannes Gutenberg-University Hospital, Mainz, Germany) who provided us with AML samples; to our colleagues from the bone marrow transplantation group and molecular diagnostics laboratory for storage of the samples and molecular analyses respectively. NR 23 TC 136 Z9 138 U1 1 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2009 VL 94 IS 1 BP 131 EP 134 DI 10.3324/haematol.13299 PG 4 WC Hematology SC Hematology GA 396LL UT WOS:000262593100020 PM 18838472 ER PT B AU Ritchie, CS Kvale, E AF Ritchie, Christine Seel Kvale, Elizabeth BE Bales, CW Ritchie, CS TI Nutrition at the End of Life: Ethical Issues SO HANDBOOK OF CLINICAL NUTRITION AND AGING, SECOND EDITION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Nutrition support; terminal illness; palliative treatment ID PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; ARTIFICIAL NUTRITION; ADVANCED DEMENTIA; HYDRATION; IMPACT; CARE AB Because of the importance of food as an integral part of life, health-care providers need to be well versed in the issues surrounding nutrition and hydration in terminal illness in order to assist patients and their families in treatment decisions. Case law in the United States considers enteral nutrition to be medical treatment and as such recognizes a patient's right to refuse artificial nutritional support. The decision about feeding should be consistent with the overall goals of care: for example, curative treatment, rehabilitative treatment or palliative treatment. C1 [Ritchie, Christine Seel] Univ Alabama, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL 35294 USA. [Kvale, Elizabeth] Univ Alabama, Div Gerontol, Birmingham, AL USA. [Kvale, Elizabeth] Birmingham VA Med Ctr, Birmingham, AL USA. RP Ritchie, CS (reprint author), Univ Alabama, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL 35294 USA. NR 24 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-384-8 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2009 BP 235 EP 244 DI 10.1007/978-1-60327-385-5_13 PG 10 WC Geriatrics & Gerontology; Gerontology; Public, Environmental & Occupational Health; Medicine, General & Internal; Nutrition & Dietetics SC Geriatrics & Gerontology; Public, Environmental & Occupational Health; General & Internal Medicine; Nutrition & Dietetics GA BJT85 UT WOS:000267149000013 ER PT B AU Kvale, E Ritchie, CS Balducci, L AF Kvale, Elizabeth Ritchie, Christine Seel Balducci, Lodovico BE Bales, CW Ritchie, CS TI Nutrition Support in Cancer SO HANDBOOK OF CLINICAL NUTRITION AND AGING, SECOND EDITION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Cancer; aging; cachexia; inflammation ID COMPREHENSIVE GERIATRIC ASSESSMENT; RESTING ENERGY-EXPENDITURE; ANOREXIA-CACHEXIA SYNDROME; LONG-TERM SURVIVAL; FISH-OIL CAPSULES; LEUKEMIA GROUP-B; QUALITY-OF-LIFE; CONTROLLED-TRIAL; NECK-CANCER; WEIGHT-LOSS AB Older cancer patients have unique qualities related to aging that place them at nutritional risk during cancer treatment. Routine assessment of nutritional risk is indicated in older cancer patients. Comprehensive geriatric assessment of older cancer patients can assist with determination of which older patients can tolerate cancer treatment with acceptable levels of morbidity and mortality. Dietary counseling and nutritional intervention (especially protein supplementation) should be incorporated into the care of nutritionally compromised older cancer patients as needed. Cancer is a frequent indication for enteral nutrition support (when there is intact gut function) or total parenteral nutrition. Management of nutritional compromise should be guided by patient-centered goals of care that incorporate the existing evidence-base into decision-making. C1 [Kvale, Elizabeth] Univ Alabama, Div Gerontol, Birmingham, AL 35294 USA. [Kvale, Elizabeth] Birmingham VA Med Ctr, Birmingham, AL USA. [Balducci, Lodovico] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Ritchie, Christine Seel] Univ Alabama, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Kvale, E (reprint author), Univ Alabama, Div Gerontol, Birmingham, AL 35294 USA. NR 99 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-384-8 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2009 BP 355 EP 372 DI 10.1007/978-1-60327-385-5_19 PG 18 WC Geriatrics & Gerontology; Gerontology; Public, Environmental & Occupational Health; Medicine, General & Internal; Nutrition & Dietetics SC Geriatrics & Gerontology; Public, Environmental & Occupational Health; General & Internal Medicine; Nutrition & Dietetics GA BJT85 UT WOS:000267149000019 ER PT B AU Katzenstein, T Ablon, JS Levy, RA AF Katzenstein, Tai Ablon, J. Stuart Levy, Raymond A. BE Levy, RA Ablon, JS TI A Naturalistic Treatment for Panic Disorder The Importance of Emotion-Focused Process SO HANDBOOK OF EVIDENCE-BASED PSYCHODYNAMIC PSYCHOTHERAPY: BRIDGING THE GAP BETWEEN SCIENCE AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID COGNITIVE-BEHAVIORAL THERAPY; PSYCHOTHERAPY PROCESS LITERATURE; COLLABORATIVE RESEARCH-PROGRAM; CONTROLLED CLINICAL-TRIALS; ANXIETY SENSITIVITY; QUALITY; LIFE C1 [Katzenstein, Tai] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ablon, J. Stuart] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02458 USA. RP Katzenstein, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM tkatzenstein@partners.org; sablon@cpsinstitute.org; RLEVY2@PARTNERS.ORG; RLEVY2@PARTNERS.ORG; sablon@cpsinstitute.org NR 43 TC 13 Z9 13 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-11-4 J9 CURR CLIN PSYCHIAT PY 2009 BP 45 EP 65 DI 10.1007/978-1-59745-444-5_3 D2 10.1007/978-1-59745-444-5 PG 21 WC Psychiatry SC Psychiatry GA BKG08 UT WOS:000267996400003 ER PT B AU Siefert, CJ Defife, JA Baity, MR AF Siefert, Caleb J. Defife, Jared A. Baity, Matthew R. BE Levy, RA Ablon, JS TI Process Measures for Psychodynamic Psychotherapy SO HANDBOOK OF EVIDENCE-BASED PSYCHODYNAMIC PSYCHOTHERAPY: BRIDGING THE GAP BETWEEN SCIENCE AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter DE Psychodynamic psychotherapy; Process research; Process measures; Psychotherapy research; Psychotherapy process ID COLLABORATIVE RESEARCH-PROGRAM; COGNITIVE-BEHAVIORAL THERAPY; PROCESS SCALES APS; NIMH TREATMENT; DEPRESSION; PATIENT; FOCUS; TIME; INTERVENTIONS; PREDICTION AB Research focusing on psychodynamic psychotherapy has grown considerably in the past three decades [1]. Recently, there has been growing interest in studying the process of psychotherapy. The present chapter provides a brief review of some measures that are useful for research into psychodynamic psychotherapy. We review ten measures designed to assess the process occurring in psychotherapy. For each measure, we provide a general description of the measure's purpose, scales, and methods, and provide some examples of how the measure has been used by researchers in the past. This chapter is not intended to be comprehensive. Instead, we provide a sample of several different types of measures and measurement methods, all of which are likely to be of interest to investigators who wish to empirically study psychodynamic psychotherapy. C1 [Siefert, Caleb J.; Baity, Matthew R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Siefert, Caleb J.] Harvard Univ, Sch Med, Boston, MA USA. [Defife, Jared A.] Massachusetts Mental Hlth Ctr, Jamaica Plain, MA USA. RP Siefert, CJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM csiefert@partners.org; jareddefife@yahoo.com; asher1208@hotmail.com NR 53 TC 7 Z9 7 U1 4 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-11-4 J9 CURR CLIN PSYCHIAT PY 2009 BP 157 EP 178 DI 10.1007/978-1-59745-444-5_7 D2 10.1007/978-1-59745-444-5 PG 22 WC Psychiatry SC Psychiatry GA BKG08 UT WOS:000267996400007 ER PT B AU Marci, CD Riess, H AF Marci, Carl D. Riess, Helen BE Levy, RA Ablon, JS TI Physiologic Monitoring in Psychodynamic Psychotherapy Research SO HANDBOOK OF EVIDENCE-BASED PSYCHODYNAMIC PSYCHOTHERAPY: BRIDGING THE GAP BETWEEN SCIENCE AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID SKIN-CONDUCTANCE RESPONSES; ELECTRODERMAL ACTIVITY; ELECTRICAL-STIMULATION; AUTONOMIC RESPONSES; PERSPECTIVE-TAKING; THERAPEUTIC CHANGE; HEART-RATE; EMPATHY; FMRI; CORTEX C1 [Marci, Carl D.; Riess, Helen] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Marci, CD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM cmarci@partners.org; hriess@partners.org NR 74 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-11-4 J9 CURR CLIN PSYCHIAT PY 2009 BP 339 EP 358 DI 10.1007/978-1-59745-444-5_14 D2 10.1007/978-1-59745-444-5 PG 20 WC Psychiatry SC Psychiatry GA BKG08 UT WOS:000267996400014 ER PT B AU Kelley, JM AF Kelley, John M. BE Levy, RA Ablon, JS TI The Perils of p-Values: Why Tests of Statistical Significance Impede the Progress of Research An Open Letter to Psychotherapy Researchers SO HANDBOOK OF EVIDENCE-BASED PSYCHODYNAMIC PSYCHOTHERAPY: BRIDGING THE GAP BETWEEN SCIENCE AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter ID PSYCHOLOGICAL-RESEARCH; CLINICAL-SIGNIFICANCE; POWER C1 [Kelley, John M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA 01915 USA. [Kelley, John M.] Endicott Coll, Dept Stat, Beverly, MA 01915 USA. RP Kelley, JM (reprint author), 376 Hale St, Beverly, MA 01915 USA. EM JKelley@Endicottt.Edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-11-4 J9 CURR CLIN PSYCHIAT PY 2009 BP 367 EP 377 DI 10.1007/978-1-59745-444-5_16 D2 10.1007/978-1-59745-444-5 PG 11 WC Psychiatry SC Psychiatry GA BKG08 UT WOS:000267996400016 ER PT B AU Lable, I AF Lable, Ira BE Levy, RA Ablon, JS TI From Psychoanalyst to Psychoanalyst/Researcher A Personal Journey SO HANDBOOK OF EVIDENCE-BASED PSYCHODYNAMIC PSYCHOTHERAPY: BRIDGING THE GAP BETWEEN SCIENCE AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Lable, I (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 805,15 Parkman St, Boston, MA 02114 USA. EM ira_lable@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-11-4 J9 CURR CLIN PSYCHIAT PY 2009 BP 379 EP 383 DI 10.1007/978-1-59745-444-5_17 D2 10.1007/978-1-59745-444-5 PG 5 WC Psychiatry SC Psychiatry GA BKG08 UT WOS:000267996400017 ER PT B AU Alonso, A AF Alonso, Anne BE Levy, RA Ablon, JS TI Clinicians' Love/Hate Relationship with Clinical Research SO HANDBOOK OF EVIDENCE-BASED PSYCHODYNAMIC PSYCHOTHERAPY: BRIDGING THE GAP BETWEEN SCIENCE AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter C1 [Alonso, Anne] Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. [Alonso, Anne] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Alonso, A (reprint author), Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-11-4 J9 CURR CLIN PSYCHIAT PY 2009 BP 385 EP 388 DI 10.1007/978-1-59745-444-5_18 D2 10.1007/978-1-59745-444-5 PG 4 WC Psychiatry SC Psychiatry GA BKG08 UT WOS:000267996400018 ER PT B AU Weiss, AP AF Weiss, Anthony P. BE Levy, RA Ablon, JS TI Measuring and Enhancing the Impact of Psychodynamic Psychotherapy Research An Open Letter to Scientists and Clinicians SO HANDBOOK OF EVIDENCE-BASED PSYCHODYNAMIC PSYCHOTHERAPY: BRIDGING THE GAP BETWEEN SCIENCE AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Room 734, Boston, MA 02114 USA. EM aweiss@partners.org NR 3 TC 1 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-11-4 J9 CURR CLIN PSYCHIAT PY 2009 BP 389 EP 393 DI 10.1007/978-1-59745-444-5_19 D2 10.1007/978-1-59745-444-5 PG 5 WC Psychiatry SC Psychiatry GA BKG08 UT WOS:000267996400019 ER PT B AU Fan, J AF Fan, Jie BE Hagg, R Kohlund, S TI Receptor Cross-Talk Mechanisms of Neutrophil Priming SO HANDBOOK OF GRANULOCYTES : CLASSIFICATION, TOXIC MATERIALS PRODUCED AND PATHOLOGY SE Human Anatomy and Physiology LA English DT Article; Book Chapter ID TOLL-LIKE RECEPTOR-4; MOBILITY GROUP BOX-1; MEDIATES HEPATIC-INJURY; MULTIPLE ORGAN FAILURE; TLR2 UP-REGULATION; FACTOR-KAPPA-B; NADPH OXIDASE; HEMORRHAGIC-SHOCK; INNATE IMMUNITY; MYD88-INDEPENDENT PATHWAY AB Severe trauma and hemorrhage renders the patient more susceptible to a second, seemingly trivial, inflammatory stimulus, the so-called "two-hit" hypothesis. The post-trauma sepsis, which involves activation of innate immunity, can lead to severe multi-organ failure (MOF) or systemic inflammatory response syndrome (SIRS), and death. Studies have suggested that inflammatory cell priming caused by a first hit is the mechanism for enhanced response of the cell to a second hit. Polymorphonuclear neutrophils (PMN) are essential effector cells of the innate immune system. The accumulation of PMN in tissue is considered a critical event in organ inflammation and injury, and has been the target of preventative strategies. PMN migration is a result of a cascade of cellular events, in which PMN, endothelial cells (EC), and macrophages (M phi) act in concert. Recent studies explored interrelated novel findings indicating that receptor cross-talk mechanisms occurring in PMN, EC, and M phi are important determinants for priming PMN migration in a sepsis setting. This chapter will focus on the detailed receptor cross-talk mechanisms underlying PMN priming. In M phi and EC, lipopolysaccharide (LPS) acts through Toll-like receptor (TLR)4 signaling to up-regulate TLR2. Oxidant signaling derived from PMN NAD(P)H oxidase enhances the TLR2 upregulation through PMN-M phi or PMN-EC interaction, resulting in an amplified release of cytokines and chemokines from the M phi and expression of adhesion molecules in the EC in response to TLR2 ligands, thereby promoting PMN migration. Furthermore, hemorrhagic shock is potent in activating PMN NAD(P)H oxidase through high-mobility group box 1 (HMGB1)-TLR4-p38 MAPK signaling, and therefore initiates the mechanisms of cell priming. On the other hand, LPS through TLR4 on PMN and phosphoinositide 3-kinase gamma (PI3K gamma) signaling down-regulates the expression of G protein-coupled receptor kinases (GRK)2 and GRK5 in response to chemokine, thereby decreases chemokine receptor desensitization and augments the PMN migration. Taken together, receptor cross-talk mechanisms are important determinants for cell priming and subsequent augmented PMN infiltration in sepsis. C1 [Fan, Jie] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Fan, J (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 86 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-582-4 J9 HUM ANAT PHYSIOL PY 2009 BP 205 EP 228 PG 24 WC Anatomy & Morphology; Physiology SC Anatomy & Morphology; Physiology GA BPC23 UT WOS:000278499700007 ER PT B AU Horan, WP Greenwood, TA Braff, DL Gur, RE Green, MF AF Horan, William P. Greenwood, Tiffany A. Braff, David L. Gur, Raquel E. Green, Michael F. BE Ritsner, MS TI The Use of Neurocognitive Endophenotypes in Large-Scale Family Genetic Studies of Schizophrenia SO HANDBOOK OF NEUROPSYCHIATRIC BIOMARKERS, ENDOPHENOTYPES AND GENES, VOL 1: NEUROPSYCHOLOGICAL ENDOPHENOTYPES AND BIOMARKERS LA English DT Article; Book Chapter DE Schizophrenia; endophenotype; neurocognition ID VERBAL WORKING-MEMORY; DORSOLATERAL PREFRONTAL CORTEX; TRAIT LINKAGE ANALYSIS; 4-MONTH FOLLOW-UP; SUSTAINED ATTENTION; NEUROPSYCHOLOGICAL DEFICITS; NONPSYCHOTIC RELATIVES; COGNITIVE NEUROSCIENCE; NAIVE PATIENTS; 1ST-DEGREE RELATIVES AB Neurocognitive deficits are core features of schizophrenia and are among the most promising candidate endophenotypes for genetic studies of this disorder. The detection of gene-endophenotype associations requires large family cohort or case-control samples that are often only possible to collect through multisite collaborations, which presents considerable challenges for the use of endophenotypes. This chapter focuses on the rationale for using neurocognitive tasks of working memory, attention, and verbal declarative memory in large-scale, collaborative efforts to apply an endophenotype approach to schizophrenia. As an example, we describe the Consortium on the Genetics of Schizophrenia (COGS), a seven-site research network that investigates the genetic architecture of these neurocognitive and other candidate endophenotypes in families with schizophrenia. After providing a brief overview of the rigorous recruitment, data acquisition, and quality assurance procedures established by the COGS, we present recent results from this project that support utility of these procedures and the validity of neurocognitive endophenotypes. We conclude with a discussion of preliminary COGS findings that point toward specific candidate genes and future directions for this and other large-scale endophenotype studies of schizophrenia. C1 [Greenwood, Tiffany A.; Braff, David L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Horan, William P.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90024 USA. [Gur, Raquel E.] Univ Penn, Dept Psychiat, Med Ctr, Philadelphia, PA 19104 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Horan, William P.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gur, Raquel E.] Univ Penn, Dept Neurol, Med Ctr, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Dept Radiol, Med Ctr, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Neuropsychiat Sect, Med Ctr, Philadelphia, PA 19104 USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90024 USA. EM horan@ucla.edu; tgreenwood@ucsd.edu; DBraff@ucsd.edu; raquel@upenn.edu; mgreen@ucla.edu NR 111 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-9463-7 PY 2009 BP 177 EP 193 DI 10.1007/978-1-4020-9464-4_12 D2 10.1007/978-1-4020-9464-4 PG 17 WC Genetics & Heredity; Neurosciences; Psychiatry; Psychology SC Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Psychology GA BKM02 UT WOS:000268464200012 ER PT S AU Kufer, KH Monz, M Scherrer, A Suss, P Alonso, F Sultan, ASA Bortfeld, T Thieke, C AF Kuefer, Karl-Heinz Monz, Michael Scherrer, Alexander Suess, Philipp Alonso, Fernando Sultan, Ahmad Saher Azizi Bortfeld, Thomas Thieke, Christian BE Pardalos, PM Romeijn, HE TI Multicriteria Optimization in Intensity Modulated Radiotherapy Planning SO HANDBOOK OF OPTIMIZATION IN MEDICINE SE Springer Series in Optimization and Its Applications LA English DT Article; Book Chapter ID BEAM ORIENTATION OPTIMIZATION; RADIATION-THERAPY; EFFICIENT SET; PROSTATE-CANCER; VECTOR MAXIMIZATION; PROGRAMMING PROBLEM; RESPIRATORY MOTION; DOSE DISTRIBUTION; MAP OPTIMIZATION; PARETO SET AB The inverse treatment planning problem of IMRT is formulated as a multicriteria optimization problem. The problem is embedded in the more general family of design problems. The concept of virtual engineering, when interpreted as an optimization paradigm for design problems, reveals favorable structural properties. The numerical complexity of large-scale instances can then be significantly reduced by an appropriate exploitation of a structural property called asymmetry. Methods to treat the multicriteria problem appropriately are developed. The methods proposed serve as ingredients for a system that incorporates (a) calculations of efficient IMRT plans possessing high clinical quality and (b) an interactive decision-making framework to select solutions. The plan calculations are done fast even for relatively large dimensions by exploiting the asymmetry property. They result in a database of plans that delimit a large set of clinically relevant plans. A sophisticated navigation scheme allows one to obtain plans that conform to the preference of the decision-maker while conveying the chances and limitations of each interaction with the system. The resulting workflow can be embedded into the clinical decision-making process to truly address the multicriteria setting inherent to IMRT planning problems. C1 [Kuefer, Karl-Heinz; Monz, Michael; Scherrer, Alexander; Suess, Philipp; Alonso, Fernando; Sultan, Ahmad Saher Azizi] ITWM, Fraunhofer Inst Ind Math, Dept Optimizat, D-67663 Kaiserslautern, Germany. [Bortfeld, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Thieke, Christian] German Canc Res Ctr, Clin Cooperat Unit Radiat Oncol, D-69120 Heidelberg, Germany. RP Kufer, KH (reprint author), ITWM, Fraunhofer Inst Ind Math, Dept Optimizat, Gottlieb Daimler Str 49, D-67663 Kaiserslautern, Germany. EM kuefer@itwm.fhg.de; monz@itwm.fhg.de; scherrer@itwm.fhg.de; suess@itwm.fhg.de; tbortfeld@partners.org; c.thieke@dkfz-heidelberg.de NR 89 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1931-6828 BN 978-0-387-09769-5 J9 SPRINGER SER OPTIM A PY 2009 VL 26 BP 123 EP 167 DI 10.1007/978-0-387-09770-1_5 PG 45 WC Mathematics, Applied; Mathematics, Interdisciplinary Applications SC Mathematics GA BJU30 UT WOS:000267166000005 ER PT B AU Chaiswing, L Oberley, TD AF Chaiswing, Luksana Oberley, Terry D. BE Meridith, AT TI Redox State and Prostate Cancer Behavior SO HANDBOOK OF PROSTATE CANCER CELL RESEARCH: GROWTH, SIGNALLING AND SURVIVAL SE Cancer Etiology Diagnosis and Treatments LA English DT Article; Book Chapter ID DAMAGE; TRANSDUCTION; PERSPECTIVE AB Cellular or tissue reduction-oxidation (redox) state is the result of the net balance of molecular reducing and oxidizing equivalents, and can be subdivided into intra-or extracellular redox state (inside or outside the cell), respectively. Under physiological conditions, redox state regulates cell metabolism, survival, and the cell cycle. Prostate cancer is the most common malignancy diagnosed in men and is the second leading cause of cancer deaths in males in the U.S.A. Many studies have documented that prostate cancer cell lines have altered levels of intracellular reactive oxygen species/reactive nitrogen species and/or antioxidant levels in relation to nonmalignant cells. This abnormal intracellular redox state may play an important role in prostate cancer cell cycle progression and cell survival through regulation of redox- modulated transcription factors. Our laboratory recently reported that prostate cancer cells in the cell cultures exhibited an increased glutathione/glutathione disulfide ratio in the media in comparison to immortalized but nonmalignant prostate epithelial cells, suggesting an alteration of extracellular redox state of prostate cancer cells. We also demonstrated that modulation of extracellular redox state by overexpression of extracellular superoxide dismutase resulted in inhibition of prostate cancer cell invasiveness through a mechanism responsive to superoxide radical and/or nitric oxide. We propose that both intra- and extracellular redox states play complementary role(s) in regulation of prostate cancer cell proliferation and/or invasion. This possible relationship between redox states may lead to the development of anti-cancer therapeutics utilizing redox-modulating compounds that are specifically designed to target prostate cancer cells and/or the prostate cancer microenviromnent. C1 [Chaiswing, Luksana] Univ Wisconsin, William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53706 USA. Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI USA. RP Chaiswing, L (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53706 USA. NR 16 TC 0 Z9 0 U1 1 U2 2 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-954-9 J9 CANCER ETIOL DIAGN T PY 2009 BP 489 EP 495 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA BNU54 UT WOS:000275598000017 ER PT J AU Freudenreich, O Tranulis, C AF Freudenreich, Oliver Tranulis, Constantin TI A Prototype Approach Toward Antipsychotic Medication Adherence in Schizophrenia SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE adherence; drug attitude; prototypes; schizophrenia; worldview ID SCHIZOAFFECTIVE DISORDER; MENTAL-ILLNESS; RATIONAL MEN; 1ST EPISODE; INSIGHT; PSYCHOSIS; NONADHERENCE; RELIABILITY; PREDICTORS; ATTITUDES AB Antipsychotic nonadherence in psychotic disorders is a vexing clinical problem. While many risk factors are associated with nonadherence, a risk factor model per se is a poor guide for clinical decisions. We propose a pragmatic clinical prototype approach that incorporates two variables, medication drug attitude and worldview (with regard to mental illness and psychiatric treatment), to create five patient prototypes of adherence: patients with good adherence for the right reasons (True Believer), with good adherence for the wrong reasons (Clinic Trouper), with reluctant and tenuous adherence (Reluctant Recruit), with passive adherence (The Coffee Guy), and with unwillingness to take medications (Constitutional Combatant). Actual patients can be compared and assigned to one of the prototypes, with the group membership predicting level and character of adherence, and suggesting specific interventions. In this scheme, drug attitude and worldview are key variables for adherence; both can be ascertained during the clinical interview and quantified with rating scales. C1 [Freudenreich, Oliver] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Tranulis, Constantin] Harvard Univ, Sch Med, Dept Social Med, Cambridge, MA 02138 USA. [Freudenreich, Oliver] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Freudenreich, O (reprint author), Freedom Trail Clin, MGH Episode & Early Psychosis Program 1, 25 Staniford St,2nd Fl, Boston, MA 02114 USA. EM ofreudenreich@partners.org NR 31 TC 8 Z9 9 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PY 2009 VL 17 IS 1 BP 35 EP 40 AR PII 908615682 DI 10.1080/10673220902724565 PG 6 WC Psychiatry SC Psychiatry GA 406AM UT WOS:000263267400003 PM 19205965 ER PT J AU Payne, JL Palmer, JT Joffe, H AF Payne, Jennifer L. Palmer, Jennifer Teitelbaum Joffe, Hadine TI A Reproductive Subtype of Depression: Conceptualizing Models and Moving Toward Etiology SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE estrogen; major depression; neurosteroids; perimenopause; postpartum; premenstrual; reproductive; serotonin ID PREMENSTRUAL DYSPHORIC DISORDER; ACUTE TRYPTOPHAN DEPLETION; PHASE SERTRALINE TREATMENT; RANDOMIZED CLINICAL-TRIAL; POSTPARTUM MOOD DISORDERS; POPULATION-BASED TWIN; QUALITY-OF-LIFE; MAJOR DEPRESSION; LUTEAL-PHASE; DOUBLE-BLIND AB The lifetime risk for major depression in women is well known to be twice the risk in men and is especially high during the reproductive years between menarche and menopause. A subset of reproductive-age women experience depressive episodes that are triggered by hormonal fluctuations. Such reproductive depressions involve episodes of depression that occur specifically during the premenstrual, postpartum, and perimenopausal phases in women. These reproductive subtypes of depression can be conceptualized as a specific biological response to the effects of hormonal fluctuations in the brain. The different types of reproductive depressions are associated with each other, have unique risk factors that are distinct from nonreproductive depression episodes, and respond to both hormonal and nonhormonal interventions. This review uses a PubMed search of relevant literature to discuss clinical, animal, and genetic evidence for reproductive depression as a specific subtype of major depression. Unique treatment options, such as hormonal interventions, are also discussed, and hypotheses regarding the underlying biology of reproductive depressionincluding interactions between the serotonergic system and estrogen, as well as specific effects on neurosteroidsare explored. This review will provide evidence supporting reproductive depression as a distinct clinical entity with specific treatment approaches and a unique biology that is separate from nonreproductive depression. C1 [Payne, Jennifer L.; Palmer, Jennifer Teitelbaum] Johns Hopkins Sch Med Psychiat, Dept Psychiat, Baltimore, MD 21205 USA. [Joffe, Hadine] Harvard Univ, Sch Med, Boston, MA USA. [Joffe, Hadine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Payne, JL (reprint author), Johns Hopkins Sch Med Psychiat, Dept Psychiat, 550 N Broadway,Suite 305, Baltimore, MD 21205 USA. EM jpayne5@jhmi.edu FU NIMH NIH HHS [K23 MH074799-01A2, K23 MH074799] NR 126 TC 47 Z9 49 U1 4 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PY 2009 VL 17 IS 2 BP 72 EP 86 AR PII 910509875 DI 10.1080/10673220902899706 PG 15 WC Psychiatry SC Psychiatry GA 434SO UT WOS:000265294600002 PM 19373617 ER EF