FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Stone, JH Khosroshahi, A Hilgenberg, A Spooner, A Isselbacher, EM Stone, JR AF Stone, John H. Khosroshahi, Arezou Hilgenberg, Alan Spooner, Amy Isselbacher, Eric M. Stone, James R. TI IgG4-Related Systemic Disease and Lymphoplasmacytic Aortitis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID AUTOIMMUNE PANCREATITIS; SCLEROSING DISEASE; ANEURYSM; PERIAORTITIS; REGURGITATION; SARCOIDOSIS; ARTERITIS; SUBCLASS; PROPOSAL AB We describe herein a patient who developed a dissection of the ascending aorta in the setting of IgG4-related systemic disease, linking IgG4-related systemic disease with a newly-recognized subset of noninfectious aortitis. At the time of aortic surgery, a transmural lymphoplasmacytic infiltrate was detected in the patient's aorta, with a principal focus of inflammation within the media. Immunohistochemical studies demonstrated that >50% of the plasma cells in the lesion stained for IgG4. By in situ hybridization, the plasma cells showed polytypic staining for kappa and lambda light chains, consistent with a polyclonal plasma cell infiltrate. Serologic evaluation revealed that the patient's IgG4 levels were elevated nearly 10-fold. Four years before aortic surgery, the patient had undergone a mediastinal lymph node biopsy. Reexamination of the lymph node revealed features consistent with IgG4-related systemic disease, which had not been recognized at the time of the original biopsy. Glucocorticoid therapy for the IgG4-related systemic disease yielded a prompt response. Recognition that IgG4-related systemic disease can involve the ascending as well as the descending abdominal aorta indicates the need for a change in the way idiopathic aortitis is regarded. This case offers new potential considerations for short- and long-term management of noninfectious aortitis, because of the frequent good response of IgG4-related systemic (disease to glucocorticoid treatment without additional therapy. Treatment of the aortitis may prevent progression of the IgG4-related systemic disease to involvement of other organs. IgG4-related systemic disease should be considered in all patients with aortitis judged to be of unknown etiology. C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St,Yawkey 2, Boston, MA 02114 USA. EM jhstone@partners.org NR 40 TC 94 Z9 100 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2009 VL 60 IS 10 BP 3139 EP 3145 DI 10.1002/art.24798 PG 7 WC Rheumatology SC Rheumatology GA 505MB UT WOS:000270696600032 PM 19790067 ER PT J AU Harris, RE Sundgren, PC Craig, AD Kirshenbaum, E Sen, A Napadow, V Clauw, DJ AF Harris, Richard E. Sundgren, Pia C. Craig, A. D. Kirshenbaum, Eric Sen, Ananda Napadow, Vitaly Clauw, Daniel J. TI Elevated Insular Glutamate in Fibromyalgia Is Associated With Experimental Pain SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; PLACEBO-CONTROLLED TRIAL; CEREBROSPINAL-FLUID; GENERAL-POPULATION; DOUBLE-BLIND; PREVALENCE; CRITERIA; CLASSIFICATION; MECHANISMS; PREGABALIN AB Objective. Central pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of functional pain syndromes such as fibromyalgia (FM). Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate (Glu) is a major cortical excitatory neurotransmitter that functions in pain neurotransmission, we undertook this study to test our hypothesis that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report. Methods. Nineteen FM patients and 14 age- and sex-matched pain-free controls underwent pressure pain testing and a proton magnetic resonance spectroscopy session in which the right anterior insula and right posterior insula were examined at rest. Results. Compared with healthy controls, FM patients had significantly higher levels of Glu (mean +/- SD 8.09 +/- 0.72 arbitrary institutional units versus 6.86 +/- 1.29 arbitrary institutional units; P = 0.009) and combined glutamine and Glu (i.e., Glx) (mean +/- SD 12.38 +/- 0.94 arbitrary institutional units versus 10.59 +/- 1.48 arbitrary institutional units; P = 0.001) within the right posterior insula. No significant differences between groups were detected in any of the other major metabolites within this region (P > 0.05 for all comparisons), and no group differences were detected for any metabolite within the right anterior insula (P > 0.11 for all comparisons). Within the right posterior insula, higher levels of Glu and Glx were associated with lower pressure pain thresholds across both groups for medium pain (for Glu, r = -0.43, P = 0.012; for Glx, r = -0.50, P = 0.003). Conclusion. Enhanced glutamatergic neurotrans-mission resulting from higher concentrations of Glu within the posterior insula may play a role in the pathophysiology of FM and other central pain augmentation syndromes. C1 [Harris, Richard E.] Univ Michigan, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48106 USA. [Craig, A. D.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Napadow, Vitaly] Massachusetts Gen Hosp, Charlestown, MA USA. RP Harris, RE (reprint author), Univ Michigan, Chron Pain & Fatigue Res Ctr, 24 Frank Lloyd Wright Dr,POB 385,Lobby M, Ann Arbor, MI 48106 USA. EM reharris@med.umich.edu RI Harris, Richard/F-1307-2011; OI Sundgren, Pia/0000-0001-9237-1236 FU US Department of the Army [DAMD-W81XWH-07-2-0050]; NIH [M01-RR-000042]; Dana Foundation; National Center for Complementary and Alternative Medicine [K01-AT-01111-01, K01-AT-002166, R01-AT-004714, P01-AT-002048] FX Supported by the US Department of the Army (grant DAMD-W81XWH-07-2-0050), the NIH (National Center for Research Resources grant M01-RR-000042), and the Dana Foundation (Award in Brain and Immuno-Imaging). Dr. Harris' work was supported by the NIH (National Center for Complementary and Alternative Medicine grant K01-AT-01111-01). Dr. Napadow's work was supported by the NIH (National Center for Complementary and Alternative Medicine grants K01-AT-002166, R01-AT-004714, and P01-AT-002048). NR 32 TC 97 Z9 99 U1 0 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2009 VL 60 IS 10 BP 3146 EP 3152 DI 10.1002/art.24849 PG 7 WC Rheumatology SC Rheumatology GA 505MB UT WOS:000270696600034 PM 19790053 ER PT J AU Schodel, J Padmapriya, P Marx, A Huang, PL Ertl, G Kuhlencordt, PJ AF Schoedel, Johannes Padmapriya, P. Marx, Alexander Huang, Paul L. Ertl, Georg Kuhlencordt, Peter J. TI Expression of neuronal nitric oxide synthase splice variants in atherosclerotic plaques of apoE knockout mice SO ATHEROSCLEROSIS LA English DT Article DE Atherosclerosis; Neuronal nitric oxide synthase; Splice variants; Nitric oxide; nNOS variants ID VASCULAR SMOOTH-MUSCLE; NO SYNTHASE; SKELETAL-MUSCLE; RNA DIVERSITY; PROTEIN; IDENTIFICATION; BRAIN; NNOS; GENE; MECHANISM AB Objective: We previously reported that deletion of brain type neuronal nitric oxide synthase-alpha (nNOS-alpha) accelerates atherosclerosis in apolipoproteinE (apoE) knockout (ko) mice. The regulation of nNOS expression is complex, involving the generation of mRNA splice variants. The current study investigates occurrence and distribution of nNOS variants in atherosclerotic lesions of apoE ko and apoE/nNOS-alpha double ko (dko) animals. Methods: Mice were fed a high fat diet for 20 weeks. Immunohistochemistry and western blot analysis were performed using antibodies detecting the carboxy terminal-, or amino terminal-residue of the nNOS protein. Confocal microscopy and in situ hybridization were used to identify the compartment of cellular expression. Results: In situ hybridization revealed the presence of nNOS-alpha and -gamma mRNA variants in apoE ko plaques, while only nNOS-gamma was detectable in apoE/nNOS dko plaques. Consistent with mRNA expression nNOS-alpha protein can be detected in the neointima of apoE ko, but not apoE/nNOS dko animals. In contrast, the carboxy terminal antibody stained the neointima and media in apoE ko vessels and showed residual nNOS immunoreactivity in apoE/nNOS dko lesions. Confocal microscopy showed predominant nNOS expression in vascular smooth muscle cells, while colocalization with macrophages was less pronounced. Conclusions: Our study shows that nNOS-alpha and -gamma splice variants are expressed in atherosclerotic plaques of apoE ko mice. nNOS variants colocalized with markers for vascular smooth muscle cells and macrophages but not for endothelial cells. Since nNOS-alpha is atheroprotective, other nNOS splice variants which differ in enzyme kinetic and subcellular localization may also influence plaque formation. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Kuhlencordt, Peter J.] Univ Munich, Div Vasc Med, Med Poliklin, D-80336 Munich, Germany. [Schoedel, Johannes; Padmapriya, P.; Ertl, Georg; Kuhlencordt, Peter J.] Univ Wurzburg, Univ Klinikum, Med Klin & Poliklin 1, D-97070 Wurzburg, Germany. [Marx, Alexander] Univ Wurzburg, Univ Klinikum, Inst Pathol, D-97070 Wurzburg, Germany. [Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. RP Kuhlencordt, PJ (reprint author), Univ Munich, Div Vasc Med, Med Poliklin, D-80336 Munich, Germany. EM peter.kuhlencordt@med.uni-muenchen.de OI Schodel, Johannes/0000-0002-3587-8839 FU Deutsche-Forschungsgemeinschaft [KU-1206(1) u. 1206(2)]; National Institute of Neurological Disorders and Stroke (NINDS) [NS33335]; National Heart, Lung, and Blood Institute (NHLBI) [HL57818] FX This work was supported by grants from the Deutsche-Forschungsgemeinschaft (KU-1206(1) u. 1206(2) 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. We thank Mrs. G. Riehl and Mrs. A. Ganscher for excellent technical assistance. NR 43 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2009 VL 206 IS 2 BP 383 EP 389 DI 10.1016/j.atherosclerosis.2009.02.033 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 512XY UT WOS:000271287000014 PM 19358992 ER PT J AU Wilker, EH Alexeeff, SE Poon, A Litonjua, AA Sparrow, D Vokonas, PS Mittleman, MA Schwartz, J AF Wilker, Elissa H. Alexeeff, Stacey E. Poon, Audrey Litonjua, Augusto A. Sparrow, David Vokonas, Pantel S. Mittleman, Murray A. Schwartz, Joel TI Candidate genes for respiratory disease associated with markers of inflammation and endothelial dysfunction in elderly men SO ATHEROSCLEROSIS LA English DT Article DE Biomarkers; Cardiovascular disease; SNPs; Inflammation; Endothelial dysfunction ID VITAMIN-D-RECEPTOR; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; POLYMORPHISM; FIBRINOGEN; LINKAGE AB Background: Inflammation and endothelial dysfunction are important risk factors for cardiovascular disease (CVD). We hypothesized that candidate genes selected for a study of asthma and chronic obstructive pulmonary disorder (COPD) are associated with markers of systemic inflammation and endothelial dysfunction in an aging population. Methods: Plasma levels of circulating C-reactive protein (CRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were obtained from 679 elderly male participants in the Normative Aging Study. Blood samples were analyzed for 202 single nucleotide polymorphisms (SNPs) in 25 candidate genes and included both haplotype tagSNPs and functional SNPs based on literature review. Data were stratified into discovery and replication cohorts for 2-stage analysis. In the discovery cohort, the relationship between biomarker level and genotype was analyzed using linear mixed effects with random intercepts for each subject and models were adjusted for age and BMI. A positive outcome in the discovery cohort was defined as a p-value <0.1 for the SNP. SNPs that met this criterion were analyzed in the replication cohort and confirmed for those which met a criterion of significance (p < 0.025). Results: In our analyses, SNPs in the CRHR1, ITPR2, and VDR genes met significance criteria. Conclusions: Our results suggest that genes thought to play a role in the pathogenesis of asthma and COPD may influence levels of serum markers of inflammation and endothelial dysfunction via novel SNP associations which have not previously been associated with cardiovascular disease. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Wilker, Elissa H.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, Boston, MA 02215 USA. [Poon, Audrey; Litonjua, Augusto A.; Schwartz, Joel] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02215 USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Dept Med, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. RP Wilker, EH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, 401 Pk Dr,Suite 415 NW, Boston, MA 02215 USA. OI Litonjua, Augusto/0000-0003-0422-5875 FU [EPA832416]; [NIEHSES015172]; [ES00002]; [ES014663]; [T32ES007069]; [NIHAG027014] FX Funding for this study was provided by EPA832416 NIEHSES015172 ES00002 ES014663 T32ES007069 and NIHAG027014. NR 28 TC 15 Z9 16 U1 0 U2 3 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 OCT PY 2009 VL 206 IS 2 BP 480 EP 485 DI 10.1016/j.atherosclerosis.2009.03.004 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 512XY UT WOS:000271287000029 PM 19409562 ER PT J AU Fugate, JMB Gouzoules, H Barrett, LF AF Fugate, Jennifer M. B. Gouzoules, Harold Barrett, Lisa Feldman TI Separating production from perception: Perceiver-based explanations for sex differences in emotion SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID FACIAL EXPRESSIONS; GENDER-DIFFERENCES; SELF-REPORT; EXPERIENCE; METAANALYSIS; INTENSITY; CONTEXT; LOOKING; SMILE AB In this commentary, we review evidence that production-based measures reveal few consistent sex differences in emotion. Further, sex differences in perceiver-based measures can be attributed to retrospective or dispositional biases. We end by discussing an alternative view that women might appear to be more emotional because they are more facile with emotion language. C1 [Fugate, Jennifer M. B.; Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Gouzoules, Harold] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. RP Fugate, JMB (reprint author), Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. EM fugatej@bc.edu; psyhg@emory.edu; barretli@bc.edu NR 31 TC 4 Z9 4 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD OCT PY 2009 VL 32 IS 5 BP 394 EP + DI 10.1017/S0140525X09990203 PG 14 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 517NL UT WOS:000271621600006 ER PT J AU Large, CH Di Daniel, E Li, XB George, MS AF Large, Charles H. Di Daniel, Elena Li, Xingbao George, Mark S. TI Neural network dysfunction in bipolar depression: clues from the efficacy of lamotrigine SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE bipolar depression; functional magnetic resonance imaging (fMRI); gamma oscillation; lamotrigine; transcranial magnetic stimulation (TMS) ID TRANSCRANIAL MAGNETIC STIMULATION; PROTEIN-KINASE-C; CORTICAL EXCITABILITY; MOOD STABILIZERS; CELLULAR PLASTICITY; DOUBLE-BLIND; LITHIUM; DISORDER; MECHANISMS; RECEPTORS AB One strategy to understand bipolar disorder is to study the mechanism of action of mood-stabilizing drugs, such as valproic acid and lithium. This approach has implicated a number of intracellular signalling elements, such as GSK beta (glycogen synthase kinase 3 beta), ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) or protein kinase C. However, lamotrigine does not seem to modulate any of these targets, which is intriguing given that its profile in the clinic differs from that of valproic acid or lithium, with greater efficacy to prevent episodes of depression than mania. The primary target of lamotrigine is the voltage-gated sodium channel, but it is unclear why inhibition of these channels might confer antidepressant efficacy. in healthy volunteers, we found that lamotrigine had a facilitatory effect on the BOLD (blood-oxygen-level-dependent) response to TMS (transcranial magnetic stimulation) of the prefrontal cortex. This effect was in contrast with an inhibitory effect of lamotrigine when TMS was applied over the motor cortex. in a follow-up study, a similar prefrontal specific facilitatory effect was observed in a larger cohort of healthy subjects, whereas valproic acid inhibited motor and prefrontal cortical TMS-induced BOLD response. In vitro, we found that lamotrigine (3-10 mu M) enhanced the power of gamma frequency network oscillations induced by kainic acid in the rat hippocampus, an effect that was not observed with valproic acid (100 mu M). These data suggest that lamotrigine has a positive effect on corticolimbic network function that may differentiate it from other mood stabilizers. The results are also consistent with the notion of corticolimbic network dysfunction in bipolar disorder. C1 [Large, Charles H.] GlaxoSmithKline SpA, Med Res Ctr, Neurosci Ctr Excellence Drug Discovery, I-37135 Verona, Italy. [Di Daniel, Elena] GlaxoSmithKline Inc, Neurosci Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England. [Li, Xingbao; George, Mark S.] Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson Vet Adm Hosp, Charleston, SC 29401 USA. RP Large, CH (reprint author), GlaxoSmithKline SpA, Med Res Ctr, Neurosci Ctr Excellence Drug Discovery, Via Fleming 4, I-37135 Verona, Italy. EM charles.h.large@gsk.com NR 52 TC 8 Z9 9 U1 1 U2 10 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD OCT PY 2009 VL 37 BP 1080 EP 1084 DI 10.1042/BST0371080 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 510DG UT WOS:000271067600028 PM 19754456 ER PT J AU Nakano, T Inoue, I Shinozaki, R Matsui, M Akatsuka, T Takahashi, S Tanaka, K Akita, M Seo, M Hokari, S Katayama, S Komoda, T AF Nakano, Takanari Inoue, Ikuo Shinozaki, Rina Matsui, Masanori Akatsuka, Toshitaka Takahashi, Seiichiro Tanaka, Kayoko Akita, Masumi Seo, Makoto Hokari, Shigeru Katayama, Shigehiro Komoda, Tsugikazu TI A possible role of lysophospholipids produced by calcium-independent phospholipase A(2) in membrane-raft budding and fission SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Alkaline phosphatase; Brush border; Caco-2; Influenza virus; MDCK; Lysophosphatidylcholine ID INTESTINAL ALKALINE-PHOSPHATASE; BRUSH-BORDER PROTEINS; INFLUENZA-VIRUS; LIPID RAFTS; LYSOPHOSPHATIDYLCHOLINE; MICRODOMAINS; ABSORPTION; SECRETION; VESICLES; RELEASE AB Phospholipase A(2) (PLA(2)) not only plays a role in the membrane vesiculation system but also mediates membrane-raft budding and fission in artificial giant liposomes. This study aimed to demonstrate the same effects in living cells. Differentiated Caco-2 cells were cultured on filter membranes. MDCK cells were challenged with Influenza virus. The MDCK cultures were harvested for virus titration with a plaque assay. Alkaline phosphatase (ALP), a membrane-raft associated glycosylphosphatidylinositol (GPI)-anchored protein, was 70% released by adding 0.2 mmol/l lysophosphatidylcholine, which was abolished by treatment with a membrane-raft disrupter, methyl-beta-cyclodextrin. Activation of calcium-independent PLA(2) (iPLA(2)) by brefeldin A increased the apical release of ALP by approximately 1.5-fold (p<0.01), which was blocked by PLA(2) inhibitor bromoenol lactone (BEL). BEL also reduced Influenza virus production into the media (<10%) in the MDCK culture. These results suggest that cells utilize inverted corn-shaped lysophospholipids generated by PLA(2) to modulate plasma membrane structure and assist the budding of raft-associated plasma membrane particles, which virus utilizes for its budding. Brush borders are enriched with membrane-rafts and undergo rapid turnover; thus, PLA(2) may be involved in the regulatory mechanism in membrane dynamism. Further, iPLA(2) may provide a therapeutic target for viral infections. (C) 2009 Elsevier B.V. All rights reserved. C1 [Nakano, Takanari; Shinozaki, Rina; Takahashi, Seiichiro; Seo, Makoto; Hokari, Shigeru; Komoda, Tsugikazu] Saitama Med Univ, Fac Med, Dept Biochem, Saitama 3500455, Japan. [Inoue, Ikuo; Katayama, Shigehiro] Saitama Med Univ, Fac Med, Dept Endocrinol & Diabet, Saitama 3500455, Japan. [Matsui, Masanori; Akatsuka, Toshitaka] Saitama Med Univ, Fac Med, Dept Microbiol, Saitama 3500455, Japan. [Tanaka, Kayoko; Akita, Masumi] Saitama Med Univ, Fac Med, Dept Morphol, Saitama 3500455, Japan. RP Nakano, T (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM nk.takanari@gmail.com NR 31 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD OCT PY 2009 VL 1788 IS 10 BP 2222 EP 2228 DI 10.1016/j.bbamem.2009.07.015 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 511FT UT WOS:000271150000026 PM 19643079 ER PT J AU Perez, VI Bokov, A Van Remmen, H Mele, J Ran, QT Ikeno, Y Richardson, A AF Perez, Viviana I. Bokov, Alex Van Remmen, Holly Mele, James Ran, Qitao Ikeno, Yuji Richardson, Arlan TI Is the oxidative stress theory of aging dead? SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Review DE Antioxidant defense; Oxidative stress; oxidative damage; Knockout mice; Transgenic mice; Longevity ID CUZN SUPEROXIDE-DISMUTASE; METHIONINE SULFOXIDE REDUCTASE; ADULT DROSOPHILA-MELANOGASTER; REPLICATIVE LIFE-SPAN; CAENORHABDITIS-ELEGANS; TRANSGENIC MICE; COPPER-ZINC; GLUTATHIONE-PEROXIDASE; GENE-EXPRESSION; MOTOR-NEURONS AB Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates (e.g., C. elegans and Drosophila) and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules). direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited to a few studies with transgenic Drosophila that overexpress antioxidant enzymes. Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod I gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice. (C) 2009 Elsevier B.V. All rights reserved. C1 [Perez, Viviana I.; Bokov, Alex; Van Remmen, Holly; Ran, Qitao; Ikeno, Yuji; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Perez, Viviana I.; Van Remmen, Holly; Ran, Qitao; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Bokov, Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78245 USA. [Van Remmen, Holly; Mele, James] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78245 USA. [Van Remmen, Holly; Ikeno, Yuji; Richardson, Arlan] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78245 USA. EM RICHARDSONA@uthscsa.edu FU National Institutes of Health [R01-AG-015908, R01-AG-023843, P01-AG19316, P01AG020591, R37-AG026557]; Department of Veterans Affairs; San Antonio Nathan Shock Center for Excellence in the Basic Biology of Aging [P30-AG-13319] FX Financial support for the lifespan data generated over the past eight years was provided by the National Institutes of Health (grants R01-AG-015908, R01-AG-023843, P01-AG19316, P01AG020591, and R37-AG026557) and the Department of Veterans Affairs (Merit Grants and a Research Enhancement Award Program [AP, HVR, QR, YI]). Special acknowledgement is given to the Animal Core of the San Antonio Nathan Shock Center for Excellence in the Basic Biology of Aging (P30-AG-13319) directed by Dr. James Nelson, Dr. Randy Strong, and Vivian Diaz. NR 104 TC 282 Z9 291 U1 1 U2 48 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD OCT PY 2009 VL 1790 IS 10 BP 1005 EP 1014 DI 10.1016/j.bbagen.2009.06.003 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 503EO UT WOS:000270516100007 PM 19524016 ER PT J AU Schatton, T Frank, NY Frank, MH AF Schatton, Tobias Frank, Natasha Y. Frank, Markus H. TI Identification and targeting of cancer stem cells SO BIOESSAYS LA English DT Review DE ABCB5; cancer stem cells; genetic lineage tracking; melanoma; tumor hierarchy ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-INITIATING CELLS; ACUTE MYELOBLASTIC-LEUKEMIA; HUMAN-MALIGNANT MELANOMA; PROGENITOR CELLS; SELF-RENEWAL; HEMATOPOIETIC PROGENITORS; PANCREATIC-CANCER; CLONOGENIC CELLS AB Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self-renewal and give rise to bulk populations of non-tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker-specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and clinical tumor progression. Importantly, proof-of-principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC-targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC. C1 [Schatton, Tobias; Frank, Markus H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Transplantat Res Ctr, Boston, MA 02115 USA. [Schatton, Tobias; Frank, Markus H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, W Roxbury, MA 02132 USA. [Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Frank, Markus H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Frank, MH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM mfrank@rics.bwh.harvard.edu RI Frank, Markus/O-1625-2014 OI Frank, Markus/0000-0002-1312-0488 FU NIH/NCI [1R01CA113796-01A1, 1R01CA138231-01, 2P50CA093683-06A20006]; American Heart Association Founders Affiliate FX Our work is supported by funds provided by the NIH/NCI (grants 1ROlCA113796-01Al, 1R01CA138231-01, and 2P50CA093683-06A20006 to M. H. F). T S. is the recipient of a Postdoctoral Fellowship Award from the American Heart Association Founders Affiliate. NR 112 TC 75 Z9 77 U1 1 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 2009 VL 31 IS 10 BP 1038 EP 1049 DI 10.1002/bies.200900058 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 506IV UT WOS:000270769400005 PM 19708024 ER PT J AU Shin, HJ Liu, T Manrai, AK Liu, XS AF Shin, Hyunjin Liu, Tao Manrai, Arjun K. Liu, X. Shirley TI CEAS: cis-regulatory element annotation system SO BIOINFORMATICS LA English DT Article ID CHIP AB We present a tool designed to characterize genome-wide protein-DNA interaction patterns from ChIP-chip and ChIP-Seq data. This stand-alone extension of our web application CEAS (cis-regulatory element annotation system) provides summary statistics on ChIP enrichment in important genomic regions such as individual chromosomes, promoters, gene bodies or exons, and infers the genes most likely to be regulated by the binding factor under study. CEAS also enables biologists to visualize the average ChIP enrichment signals over specific genomic regions, particularly allowing observation of continuous and broad ChIP enrichment that might be too subtle to detect from ChIP peaks alone. C1 [Shin, Hyunjin; Liu, Tao; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Manrai, Arjun K.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM shin@jimmy.harvard.edu; xsliu@jimmy.harvard.edu RI Liu, Tao/G-3585-2010; OI Liu, Tao/0000-0002-8818-8313; Liu, Tao/0000-0003-0446-9001 NR 5 TC 186 Z9 187 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2009 VL 25 IS 19 BP 2605 EP 2606 DI 10.1093/bioinformatics/btp479 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 502HB UT WOS:000270446400022 PM 19689956 ER PT J AU Arai, K Lo, EH AF Arai, Ken Lo, Eng H. TI Oligovascular Signaling in White Matter Stroke SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Review DE oligovascular signaling; white matter injury; stroke; oligovascular niche; oligodendrocyte; neurovascular unit ID GROWTH-FACTOR-I; OLIGODENDROCYTE PROGENITOR CELLS; BLOOD-BRAIN-BARRIER; CEREBRAL ENDOTHELIAL-CELLS; FREE-RADICAL SCAVENGERS; CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; SMALL-VESSEL DISEASE; ISCHEMIC-INJURY; NMDA RECEPTORS AB Stroke is one of the leading causes of death and disability in developed countries. Since protecting neurons alone is not sufficient for stroke therapy, research has shifted to the rescue of multiple cell types in the brain. In particular, attention has focused on the study of how cerebral blood vessels and brain cells communicate with each other. Recent findings suggest that cerebral endothelial cells may secrete trophic factors that nourish neighboring cells. Although data are strongest in terms of supporting endothelial-neuronal interactions, it is likely that similar interactions occur in white matter as well. In this mini-review, we summarize recent advances in the dissection of cell-cell interactions in white matter. We examine two key concepts. First, trophic interactions between vessels and oligodendrocytes (OLGs) and oligodendrocyte precursor cells (OPCs) play critical roles in white matter homeostasis. Second, cell-cell trophic coupling is disturbed under diseased conditions that incur oxidative stress. White matter pathophysiology is very important in stroke. A deeper understanding of the mechanisms of oligovascular signaling in normal and pathologic conditions may lead us to new therapeutic targets for stroke and other neurodegenerative diseases. C1 [Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arai, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH E 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU Deane Foundation; American Heart Association; NIH [R37-NS37074, R01-NS48422, R01-NS53560, P50-NS10828, P01-NS55104] FX Supported in part by the Deane Foundation, American Heart Association and NIH grants R37-NS37074, R01-NS48422, R01-NS53560, P50-NS10828 and P01-NS55104. NR 91 TC 24 Z9 24 U1 0 U2 4 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD OCT PY 2009 VL 32 IS 10 BP 1639 EP 1644 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 502GP UT WOS:000270444500001 PM 19801821 ER PT J AU New, AS Fan, J Murrough, JW Liu, X Liebman, RE Guise, KG Tang, CY Charney, DS AF New, Antonia S. Fan, Jin Murrough, James W. Liu, Xun Liebman, Rachel E. Guise, Kevin G. Tang, Cheuk Y. Charney, Dennis S. TI A Functional Magnetic Resonance Imaging Study of Deliberate Emotion Regulation in Resilience and Posttraumatic Stress Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alexithymia; PTSD; resilience; sexual assault; trauma ID CORTICOLIMBIC BLOOD-FLOW; CHILDHOOD SEXUAL-ABUSE; SCRIPT-DRIVEN IMAGERY; NEGATIVE AFFECT; TRAUMA; PTSD; RESPONSES; SUPPRESSION; ALEXITHYMIA; PREVALENCE AB Background: Sexual violence is an important public health problem in the United States, with 13% to 26% of women reporting a history of sexual assault. While unfortunately common, there is substantial individual variability in response to sexual assault. Approximately half of rape victims develop posttraumatic stress disorder (PTSD), while others develop no psychopathology (e.g., trauma-exposed non-PTSD). In this project, we examined the neural mechanisms underlying differences in response to sexual violence, focusing specifically on the deliberate modification of emotional responses to negative stimuli. Methods: Using functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) response, we examined the neural circuitry underlying effortful modification of emotional responses to negative pictures in 42 women: 14 with PTSD after sexual trauma, 14 with no psychiatric diagnosis after sexual trauma, and 14 nontraumatized control subjects. Results: In response to deliberate attempts to downregulate emotional responses, nontraumatized healthy control subjects were more successful than either trauma-exposed group (PTSD or non-PTSD) in downregulating responses to the negative pictures as measured by subjective rating and BOLD response in regions of prefrontal cortex (PFC). In contrast, after deliberate attempts to upregulate emotional responses, regions of PFC were activated by trauma-exposed non-PTSD subjects more than by healthy control subjects or PTSD subjects. Conclusions: Successful downregulation of emotional responses to negative stimuli appears to be impaired by trauma exposure. In contrast, the ability to upregulate emotional responses to negative stimuli may be a protective factor in the face of trauma exposure and associated with resilience. C1 [New, Antonia S.] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, Bronx, NY USA. [New, Antonia S.; Fan, Jin; Murrough, James W.; Liu, Xun; Liebman, Rachel E.; Guise, Kevin G.; Tang, Cheuk Y.; Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP New, AS (reprint author), Mt Sinai Sch Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM antonia.new@mssm.edu RI Fan, Jin/A-6716-2009; Murrough, James/J-7129-2013; Liu, Xun/C-2400-2009 OI Fan, Jin/0000-0001-9630-8330; Murrough, James/0000-0001-6286-1242; Liu, Xun/0000-0003-1366-8926 FU National Center for Research Resources at the National Institutes of Health [5-M01 RR00071] FX This material is the result of work, supported with resources and the use of facilities at the Peters Veterans Affairs Medical Center and by a Grant (5-M01 RR00071) for the Mount Sinai General Clinical Research Center from the National Center for Research Resources at the National Institutes of Health NR 60 TC 79 Z9 81 U1 8 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2009 VL 66 IS 7 BP 656 EP 664 DI 10.1016/j.biopsych.2009.05.020 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 496NQ UT WOS:000269981700006 PM 19589502 ER PT J AU Gentil, AF Eskandar, EN Marci, CD Evans, KC Dougherty, DD AF Gentil, Andre Felix Eskandar, Emad N. Marci, Carl David Evans, Karleyton Conroy Dougherty, Darin Dean TI Physiological Responses to Brain Stimulation During Limbic Surgery: Further Evidence of Anterior Cingulate Modulation of Autonomic Arousal SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anterior cingulotomy; autonomic nervous system; cingulate cortex; electrodermal activity; subcauclate tractotomy ID FUNCTIONAL MAGNETIC-RESONANCE; SKIN-CONDUCTANCE RESPONSES; CEREBRAL-BLOOD-FLOW; PREFRONTAL CORTEX; ELECTRODERMAL ACTIVITY; MAJOR DEPRESSION; NEURAL ACTIVITY; POSITIVE AFFECT; EMOTION; FMRI AB Background: In view of conflicting neuroimaging results regarding autonomic-specific activity within the anterior cingulate cortex (ACC), we investigated autonomic responses to direct brain stimulation during sterecitactic limbic surgery. Methods: Skin conductance activity and accelerative heart rate responses to multi-voltage stimulation of the ACC (n = 7) and paralimbic subcauclate (n = 5) regions were recorded during bilateral anterior cingulotomy and bilateral subcauclate tractotomy (in patients that had previously received an adequate lesion in the ACC), respectively. Results: Stimulations in both groups were accompanied by increased autonomic arousal. Skin conductance activity was significantly increased during ACC stimulations compared with paralimbic targets at 2 V (2.34 +/- .68 [score in microSiemens +/- SE] vs. .34 +/- .09, p = .013) and 3 V (3.52 +/- .86 vs. 1.12 +/- .37, p = .036), exhibiting a strong "voltage-response" relationship between stimulus magnitude and response amplitude (difference from 1 to 3 V = 1.15 +/- .90 vs. 3.52 +/- .86, p = .041). Heart rate response was less indicative of between-group differences. Conclusions: This is the first study of its kind aiming at seeking novel insights into the mechanisms responsible for central autonomic modulation. It supports a concept that interregional interactions account for the coordination of autonomic arousal. C1 [Gentil, Andre Felix; Marci, Carl David; Evans, Karleyton Conroy; Dougherty, Darin Dean] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Eskandar, Emad N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. [Gentil, Andre Felix] Univ Sao Paulo, Sch Med, Clin Hosp, Dept Psychiat, Sao Paulo, Brazil. [Gentil, Andre Felix] Univ Sao Paulo, Sch Med, Clin Hosp, Inst Psychiat, Sao Paulo, Brazil. RP Gentil, AF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA. EM afgentil@gmail.com FU Howard Hughes Medical Institute; National Association for Research on Schizophrenia and Depression (NARSAD); CePhalon; Cyheronics; Medtronic; Northstar Neuroscience; Pfizer; Forest FX D. Gentil reported no biomedical financial interests or potential conflicts of interest. Dr. discloses research support from the Howard Hughes Medical Institute. Dr. Marci was supported by a grant from The National Association for Research on Schizophrenia and Depression (NARSAD). Dr. Evans discloses honoraria from Northstar Neuroscience and research support from CePhalon, Cyheronics, Medtronic, Northstar Neuroscience, and Pfizer. Dr. Dougherty discloses honoraria from Cyberonics and Mcneil and research support from Cephalon, Eli Lilly, Forest. Medtronic, Northstar Neuroscience, and Pfizer. NR 49 TC 10 Z9 10 U1 6 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2009 VL 66 IS 7 BP 695 EP 701 DI 10.1016/j.biopsych.2009.05.009 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 496NQ UT WOS:000269981700012 PM 19545859 ER PT J AU Yehuda, R Cai, GQ Golier, JA Sarapas, C Galea, S Ising, M Rein, T Schmeidler, J Muller-Myhsok, B Holsboer, F Buxbaum, JD AF Yehuda, Rachel Cai, Guiqing Golier, Julia A. Sarapas, Casey Galea, Sandro Ising, Marcus Rein, Theo Schmeidler, James Mueller-Myhsok, Bertram Holsboer, Florian Buxbaum, Joseph D. TI Gene Expression Patterns Associated with Posttraumatic Stress Disorder Following Exposure to the World Trade Center Attacks SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Childhood trauma; cortisol; gene expression; human FKBP5 protein; posttraumatic stress disorders; September 11 terrorist attacks ID FKBP5; POLYMORPHISMS; COHORT; SCALE; PTSD AB Background: Although genetic risk factors for posttraumatic stress disorder (PTSD) in similarly traumatized cohorts can be confounded with risk for type of exposure, the primary risk for exposure to the 9/11 attack on New York City was proximity, allowing study of PTSD risk in a sample that is not confounded by exposure-related risk. Methods: Thirty-five Caucasians (15 with PTSD, stratified for exposure, age, and gender) were selected from a population-representative sample of persons exposed to the attack from which longitudinal data had been collected in four previous waves. Whole blood gene expression and cortisol levels were obtained. Results: Seventeen probe sets were differentially expressed in PTSD. Identified genes were generally involved in hypothalamic-pituitary-adrenal (HPA) axis, signal transduction, or brain and immune cell function. FKBP5, a modulator of glucocorticoid receptor (GR) sensitivity, showed reduced expression in PTSD, consistent with enhanced GR responsiveness. FKBP5 expression was predicted by cortisol when entered with PTSD severity in regression analysis. Quantitative polymerase chain reaction confirmed significant reductions in FKBP5. Also less expressed in PTSD were STAT5B, a direct inhibitor of GR, and major histocompatibility complex (MHC) Class II. Conclusions: Consistent with observations of HPA axis dysfunction in PTSD, several genes involved in glucocorticoid signaling are differentially expressed among those with current PTSD. C1 [Yehuda, Rachel; Golier, Julia A.; Sarapas, Casey; Schmeidler, James] James J Peters Vet Affairs Med Ctr, Bronx, NY 10458 USA. [Yehuda, Rachel; Golier, Julia A.; Sarapas, Casey; Schmeidler, James] Mt Sinai Sch Med, Bronx, NY USA. [Cai, Guiqing; Buxbaum, Joseph D.] Mt Sinai Sch Med, New York, NY USA. [Galea, Sandro] Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48109 USA. [Ising, Marcus; Rein, Theo; Mueller-Myhsok, Bertram; Holsboer, Florian] Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, 526 OOMH PTSD 116-A,130 W Kingsbridge Rd, Bronx, NY 10458 USA. EM rachel.yehuda@va.gov RI Muller-Myhsok, Bertram/A-3289-2013; OI Buxbaum, Joseph/0000-0001-8898-8313; Rein, Theo/0000-0003-2850-4289 FU NCRR NIH HHS [5MO1 RR00071]; NIMH NIH HHS [1R56MH077321-01] NR 20 TC 120 Z9 122 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2009 VL 66 IS 7 BP 708 EP 711 DI 10.1016/j.biopsych.2009.02.034 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 496NQ UT WOS:000269981700015 PM 19393990 ER PT J AU Marks, DI Ballen, K Logan, BR Wang, ZW Sobocinski, KA Bacigalupo, A Burns, LJ Gupta, V Ho, V McCarthy, PL Ringden, O Schouten, HC Seftel, M Rizzo, JD AF Marks, David I. Ballen, Karen Logan, Brent R. Wang, Zhiwei Sobocinski, Kathleen A. Bacigalupo, Andrea Burns, Linda J. Gupta, Vikas Ho, Vincent McCarthy, Philip L. Ringden, Olle Schouten, Harry C. Seftel, Matthew Rizzo, J. Douglas TI The Effect of Smoking on Allogeneic Transplant Outcomes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Smoking effect; Hematopoietic cell transplantation; Outcomes; Chronic myelogenous leukemia; Dose effect ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; UNRELATED DONORS; RISK; COMPLICATIONS; INEQUALITIES; PREDICTORS; RECIPIENTS; MORTALITY AB Using the Center for Internaitonal Blood and Marrow Transplant Research (CIBMTR) data, we compared the transplant outcomes of patients with chronic myelogenous leukemia (CML) who were nonsmokers (NS) and past or current smokers (PCS). There were 2193 NS and 625 PCS who received matched sibling and unrelated donor allografts for CML in first chronic phase. We looked for dose effects and identified low and high dose smoking groups (>10 pack years, >1 pack per day). Outcomes were adjusted for known prognostic variables including the European Group for Blood and Marrow Transplant (EBMT) risk score. In multivariate analyses of sibling allograft recipients, relapse risk (RR) was higher (RR = 1.67, P = .003) in smokers than NS, but the dose effects were not consistent. High-dose smokers experienced a 50% treatment-related mortality (TRM) versus 28% in the NS group at 5 years on univariate analysis, and the RR was 1.57 (P = .005) on multivariate analysis. Overall survival (OS) at 5 years was 68% in NS versus 62% in the low-dose smoking group versus 50% in the high-dose smoking group (P < .001). Smoking did not significantly affect outcomes in unrelated donor recipients, but numbers were smaller. High-dose smoking is associated with a reduction in OS in patients having sibling allografts for CML. A prospective study with detailed demographic, pulmonary function, and quality-of-life data would improve our understanding of this issue. C1 [Logan, Brent R.; Wang, Zhiwei; Sobocinski, Kathleen A.; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Marks, David I.] Univ Hosp Bristol, Bristol, Avon, England. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bacigalupo, Andrea] San Martino Hosp, Genoa, Italy. [Burns, Linda J.] Univ Minnesota, Minneapolis, MN USA. [Gupta, Vikas] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Ho, Vincent] Dana Farber Canc Inst, Boston, MA 02115 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Ringden, Olle] Karolinska Inst, Stockholm, Sweden. [Schouten, Harry C.] Univ Hosp Maastricht, Maastricht, Netherlands. [Seftel, Matthew] CancerCare Manitoba, Winnipeg, MB, Canada. RP Rizzo, JD (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM rizzo@mcw.edu FU NCI NIH HHS [U24 CA076518-12, U24 CA076518, U24-CA76518] NR 21 TC 12 Z9 12 U1 0 U2 4 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 OCT PY 2009 VL 15 IS 10 BP 1277 EP 1287 DI 10.1016/j.bbmt.2009.06.005 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 499WK UT WOS:000270257200008 PM 19747636 ER PT J AU Deardorff, R Spinale, FG AF Deardorff, Rachael Spinale, Francis G. TI Cytokines and matrix metalloproteinases as potential biomarkers in chronic heart failure SO BIOMARKERS IN MEDICINE LA English DT Review DE chronic heart failure; cytokines; matrix metalloproteinases; tissue inhibitors of matrix metalloproteinases ID TUMOR-NECROSIS-FACTOR; IDIOPATHIC DILATED CARDIOMYOPATHY; ACUTE MYOCARDIAL-INFARCTION; FACTOR-ALPHA; CIRCULATING LEVELS; TISSUE INHIBITORS; PROINFLAMMATORY CYTOKINES; SYSTOLIC DYSFUNCTION; EJECTION FRACTION; SOLUBLE RECEPTORS AB Heart failure (HF) is accompanied by the upregulation of bioactive signaling molecules, known as cytokines, and a family of downstream proteases, matrix metalloproteinases (MMPs). It is now apparent that these molecules contribute to adverse myocardial remodeling during HF. Elevated levels of cytokines and MMPs exist in the myocardium and can subsequently spill over into the systemic circulation. The purpose of this article is to examine clinical studies of HF that have quantified levels of different types of cytokines, MMPs and endogenous tissue inhibitors of MMPs in relation to this disease process. HF is a complex syndrome that can develop from various etiologies and can be characterized into two distinct phenotypes: systolic and diastolic. This article will present recent clinical studies that have identified significant differences between the cytokine and MMP circulating profile of systolic and diastolic HF patients. In general, elevated levels of cytokines and MMPs exist in systolic HF patients when compared with diastolic HF patients, whereas diastolic HF patients have elevated levels of cytokines and MMPs when compared with controls. Therefore, future studies distinguishing between HF phenotypes may provide more consistent results in determining possible analytes to be used as biomarkers. Furthermore, this article will emphasize why standardization of analytical techniques and establishment of referent cytokine and MMP levels are necessary if these analytes are to be used as biomarkers for the diagnosis, prognosis and evaluation of treatment in the context of HF. C1 [Deardorff, Rachael] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Deardorff, R (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA. FU NIH [HL-59165]; Ralph H Johnson Veterans' Association Medical Center FX This article was made possible through research funding from the NIH Grant HL-59165 and Merit Review Funding from the Ralph H Johnson Veterans' Association Medical Center. 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 NR 74 TC 13 Z9 14 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD OCT PY 2009 VL 3 IS 5 BP 513 EP 523 DI 10.2217/BMM.09.60 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 511CA UT WOS:000271140300008 PM 20161487 ER PT J AU Cook, AJ Gold, DR Li, Y AF Cook, Andrea J. Gold, Diane R. Li, Yi TI Spatial Cluster Detection for Repeatedly Measured Outcomes while Accounting for Residential History SO BIOMETRICAL JOURNAL LA English DT Article DE Asthma, Cumulative residuals, Repeated measured; Spatial cluster detection; Wheeze ID CHILDREN; MODEL AB Spatial Cluster detection has become all important methodology ill quantifying the effect of hazardous exposures. Previous methods have focused oil cross-sectional outcomes that are binary or continuous There are virtually no spatial Cluster detection methods proposed for longitudinal outcomes. This paper proposes a new spatial cluster detection method for repeated outcomes using cumulative geographic residuals A major advantage of this method is its ability to readily incorporate information Oil Study participants relocation, Which Most Cluster detection statistics cannot. Application of these methods will be illustrated by the Home Allergens and Asthma prospective cohort study analyzing the relationship between environmental exposures and repeated measured outcome. Occurrence of wheeze in the last 6 months, while taking into account mobile locations C1 [Cook, Andrea J.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Cook, Andrea J.] Univ Washington, Dept Biostat, Seattle, WA 98105 USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Gold, Diane R.] Harvard Univ, Sch Med, Boston, MA USA. [Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cook, AJ (reprint author), Grp Hlth Res Inst, Seattle, WA 98101 USA. FU NIH [RO1 AI/EHS 35786, RO1 CA95747] FX Diane R Gold Was supported by NIH RO1 AI/EHS 35786 and Yi Li was supported by NIH RO1 CA95747. NR 21 TC 3 Z9 3 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD OCT PY 2009 VL 51 IS 5 BP 801 EP 818 DI 10.1002/bimj.200800269 PG 18 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 516QE UT WOS:000271556500005 PM 19760635 ER PT J AU Lin, HZ Zhou, XH AF Lin, Huazhen Zhou, Xiao-Hua TI A semiparametric 2-part mixed-effects heteroscedastic transformation model for correlated right-skewed semicontinuous data SO BIOSTATISTICS LA English DT Article DE Laplace approximation; Mixed effects; Right skewed; Semicontinuous; Semiparametric; Transformation model ID GENERALIZED LINEAR-MODELS; REGRESSION-MODEL; RETRANSFORMATION; SAMPLES; TRIAL; ZERO AB In longitudinal or hierarchical structure studies, we often encounter a semicontinuous variable that has a certain proportion of a single value and a continuous and skewed distribution among the rest of values. In this paper, we propose a new semiparametric 2-part mixed-effects transformation model to fit correlated skewed semicontinuous data. In our model, we allow the transformation to be nonparametric. Fitting the proposed model faces computational challenges due to intractable numerical integrations. We derive the estimates for the parameter and the transformation function based on an approximate likelihood, which has high-order accuracy but less computational burden. We also propose an estimator for the expected value of the semicontinuous outcome on the original scale. Finally, we apply the proposed methods to a clinical study on effectiveness of a collaborative care treatment on late-life depression on health care costs. C1 [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Stat, Seattle, WA 98195 USA. [Lin, Huazhen] Sichuan Univ, Dept Math, Chengdu 610064, Sichuan, Peoples R China. RP Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. EM azhou@u.washington.edu NR 29 TC 5 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 EI 1468-4357 J9 BIOSTATISTICS JI Biostatistics PD OCT PY 2009 VL 10 IS 4 BP 640 EP 658 DI 10.1093/biostatistics/kxp019 PG 19 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 493KI UT WOS:000269735000004 PM 19546166 ER PT J AU Stone, RM DeAngelo, DJ AF Stone, Richard M. DeAngelo, Daniel J. TI Screens, iron, and leukemia SO BLOOD LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; DIFFERENTIATION; COMBINATION C1 [Stone, Richard M.; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2009 VL 114 IS 14 BP 2857 EP 2858 DI 10.1182/blood-2009-08-234161 PG 4 WC Hematology SC Hematology GA 501MX UT WOS:000270387100005 PM 19797531 ER PT J AU Bitting, RL Bent, S Li, YM Kohlwes, J AF Bitting, Rhonda L. Bent, Stephen Li, Yongmei Kohlwes, Jeffrey TI The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE acquired coagulation disorders; hemophilia and other bleeding disorders; immunotherapy; other coagulation inhibitors ID FACTOR-VIII INHIBITORS; PORCINE FACTOR-VIII; IMMUNOSUPPRESSIVE THERAPY; EXPERIENCE; MANAGEMENT; PREDNISONE; RITUXIMAB; INFUSION; REGIMEN; COHORT AB The inhibition of factor VIII by autoantibody development, or acquired hemophilia, occurs in approximately one person per million each year and can cause life-threatening bleeding. Due to the disease rarity, there are no randomized studies addressing prognostic features and treatment. The goal of this study is to identify prognostic indictors in acquired hemophilia to guide treatment choices. MEDLINE and EMBASE search from 1985-2008 retrieved 32 studies with detailed clinical information on five or more patients with acquired hemophilia. Univariate and multivariate analysis of the effects of age, sex, underlying condition, inhibitor titer, and treatment regimen were evaluated with regards to complete remission and death. A total of 32 studies containing 359 patients with acquired hemophilia were included in the analysis. The all-cause mortality rate in this cohort was 21%. Multivariate analyses revealed that patients more likely to die are the elderly [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.32-4.36] and those with underlying malignancy (OR 2.76, CI 1.38-5.50). Early achievement of complete remission resulted in improved survival. Complete remission occurred in 94% of patients receiving combination chemotherapy, 82% receiving dual therapy, and 68% receiving steroids alone. Patients receiving immunosuppression had reduced odds of persistent hemophilia, with combination chemotherapy being the most efficacious (OR 0.04, CI 0.01-0.23) and steroid therapy alone being the least (OR 0.38, CI 0.140.94). In acquired hemophilia, increased age, underlying malignancy, and lack of complete remission are risk factors for death. Although the included studies were not randomized, patients treated with combination chemotherapy had the greatest odds of remission and the lowest odds of death. Blood Coagul Fibrinolysis 20:517-523 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Bitting, Rhonda L.; Bent, Stephen; Kohlwes, Jeffrey] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Li, Yongmei] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Bitting, RL (reprint author), 521 Pamassus Ave,Suite C-430, San Francisco, CA 94143 USA. EM rhonda.bitting@ucsf.edu NR 42 TC 27 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD OCT PY 2009 VL 20 IS 7 BP 517 EP 523 DI 10.1097/MBC.0b013e32832ca388 PG 7 WC Hematology SC Hematology GA 506HC UT WOS:000270764800006 PM 19644360 ER PT J AU Yokoe, D Casper, C Dubberke, E Lee, G Munoz, P Palmore, T Sepkowitz, K Young, JAH Donnelly, JP AF Yokoe, D. Casper, C. Dubberke, E. Lee, G. Munoz, P. Palmore, T. Sepkowitz, K. Young, J-A H. Donnelly, J. P. TI Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated SO BONE MARROW TRANSPLANTATION LA English DT Article DE infection control; hematopoietic cell transplantation C1 [Yokoe, D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yokoe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Casper, C.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Dubberke, E.] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. [Lee, G.] Childrens Hosp, Boston, MA 02115 USA. [Munoz, P.] Univ Madrid, Hosp Gen Gregorio Maranon, Madrid 3, Spain. [Palmore, T.] NIH, Bethesda, MD 20892 USA. [Sepkowitz, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Young, J-A H.] Univ Minnesota, Div Infect Dis, Minneapolis, MN USA. [Donnelly, J. P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. RP Yokoe, D (reprint author), Brigham & Womens Hosp, 181 Longwood Ave, Boston, MA 02115 USA. EM deborah.yokoe@channing.harvard.edu RI Young, Jo-Anne/G-2617-2013; OI Young, Jo-Anne/0000-0003-4182-341X; Munoz Garcia, Patricia Carmen/0000-0001-5706-5583; Donnelly, J Peter/0000-0002-8521-335X NR 0 TC 25 Z9 25 U1 0 U2 1 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 OCT PY 2009 VL 44 IS 8 BP 495 EP 507 DI 10.1038/bmt.2009.261 PG 13 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 512KJ UT WOS:000271247300008 PM 19861984 ER PT J AU Yokoe, D Casper, C Dubberke, E Lee, G Munoz, P Palmore, T Sepkowitz, K Young, JAH Donnelly, JP AF Yokoe, D. Casper, C. Dubberke, E. Lee, G. Munoz, P. Palmore, T. Sepkowitz, K. Young, J-A H. Donnelly, J. P. TI Safe living after hematopoietic cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE foods; activities; hematopoietic cell transplantation C1 [Yokoe, D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yokoe, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Casper, C.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Dubberke, E.] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. [Lee, G.] Childrens Hosp, Boston, MA 02115 USA. [Munoz, P.] Univ Madrid, Hosp Gen Gregorio Maranon, Madrid 3, Spain. [Palmore, T.] NIH, Bethesda, MD 20892 USA. [Sepkowitz, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Young, J-A H.] Univ Minnesota, Div Infect Dis, Minneapolis, MN USA. [Donnelly, J. P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. RP Yokoe, D (reprint author), Brigham & Womens Hosp, 181 Longwood Ave, Boston, MA 02115 USA. EM deborah.yokoe@channing.harvard.edu RI Young, Jo-Anne/G-2617-2013; OI Young, Jo-Anne/0000-0003-4182-341X; Munoz Garcia, Patricia Carmen/0000-0001-5706-5583; Donnelly, J Peter/0000-0002-8521-335X NR 0 TC 11 Z9 11 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 OCT PY 2009 VL 44 IS 8 BP 509 EP 519 DI 10.1038/bmt.2009.262 PG 11 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 512KJ UT WOS:000271247300009 PM 19861985 ER PT J AU Nguyen, PL Chen, RC Clark, JA Cormack, RA Loffredo, M McMahon, E Nguyen, AU Suh, WW Tempany, CM D'Amico, AV AF Nguyen, Paul L. Chen, Ronald C. Clark, Jack A. Cormack, Robert A. Loffredo, Marian McMahon, Elizabeth Nguyen, Angela U. Suh, W. Warren Tempany, Clare M. D'Amico, Anthony V. TI Patient-reported quality of life after salvage brachytherapy for radio-recurrent prostate cancer: A prospective Phase II study SO BRACHYTHERAPY LA English DT Article DE Quality of life; Salvage therapy; Brachytherapy; Magnetic resonance imaging; Prostate cancer; Prostate-specific antigen ID RADIATION-THERAPY; INTERSTITIAL BRACHYTHERAPY; SELECT PATIENTS; ADENOCARCINOMA; REIRRADIATION; RADIOTHERAPY; OUTCOMES; FAILURE AB BACKGROUND: Patient-reported quality of life (QOL) after salvage brachytherapy for radiorecurrent prostate cancer has not been well-characterized prospectively. METHODS: We examined 25 men who recurred after primary radiotherapy for prostate cancer and received MRI-guided salvage brachytherapy as part of it prospective Phase 11 study. These patients received prospectively a validated patient-reported QOL questionnaire to fill out at baseline, as well as 3, 15, and 27 months after re-irradiation to determine the degree of sexual, bowel, and urinary dysfunction (maximum dysfunction score = 100). RESULTS: On average, sexual function continued to decline with time, and patients had significantly worse Sexual function scores at 27 months than baseline (p = 0.01). Although bowel and urinary symptoms worsened acutely at 3 or 15 months, they showed on average some improvement by 27 months, and there were no significant differences between baseline and 27-month urinary or bowel scores. An interval to re-irradiation less than 4.5 years and prior brachytherapy were each associated significantly with the largest decrements in bowel function (p = 0.035). CONCLUSION: Similar to the patterns seen in the de novo setting, patients who receive salvage brachytherapy report a worsening of bowel and urinary symptoms followed by some improvement by 27 months, while sexual function steadily declines over time. Interval to re-irradiation and type of prior radiation received may be used to counsel and optimize selection of men for salvage brachytherapy with regard to QOL endpoints. (C) 2009 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Nguyen, Paul L.; Chen, Ronald C.] Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Cormack, Robert A.; Loffredo, Marian; Nguyen, Angela U.; Suh, W. Warren; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Cormack, Robert A.; Loffredo, Marian; Nguyen, Angela U.; Suh, W. Warren; D'Amico, Anthony V.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Tempany, Clare M.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Nguyen, Paul L.; Chen, Ronald C.; Cormack, Robert A.; Loffredo, Marian; McMahon, Elizabeth; Nguyen, Angela U.; Suh, W. Warren; Tempany, Clare M.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Boston, MA USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. RP Nguyen, PL (reprint author), Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu OI Clark, Jack/0000-0002-7424-1670; Cormack, Robert/0000-0001-5553-9984 FU NCI NIH HHS [P01 CA067165]; NCRR NIH HHS [U41 RR019703]; NIA NIH HHS [R01 AG019513] NR 17 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD OCT-DEC PY 2009 VL 8 IS 4 BP 345 EP 352 DI 10.1016/j.brachy.2009.01.004 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 511OG UT WOS:000271174500003 PM 19428311 ER PT J AU O'Connor, MF Bower, JE Cho, HJ Creswell, JD Dimitrov, S Hamby, ME Hoyt, MA Martin, JL Robles, TF Sloan, EK Thomas, KS Irwin, MR AF O'Connor, Mary-Frances Bower, Julie E. Cho, Hyong Jin Creswell, J. David Dimitrov, Stoyan Hamby, Mary E. Hoyt, Michael A. Martin, Jennifer L. Robles, Theodore F. Sloan, Erica K. Thomas, KaMala S. Irwin, Michael R. TI To assess, to control, to exclude: Effects of biobehavioral factors on circulating inflammatory markers SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Review DE Inflammation; Exclusion criteria; Biobehavioral; SES; Exercise; Body mass index; Interleukin ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; CARDIOVASCULAR RISK-FACTORS; MODERATE ALCOHOL-CONSUMPTION; HORMONE REPLACEMENT THERAPY; MAJOR-DEPRESSIVE-DISORDER; INTERLEUKIN-1 RECEPTOR ANTAGONIST; HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CROSSOVER TRIAL; LOW SOCIOECONOMIC-STATUS AB Behavioral scientists have increasingly included inflammatory biology as mechanisms in their investigation of psychosocial dynamics on the pathobiology of disease. However, a lack of standardization of inclusion and exclusion criteria and assessment of relevant control variables impacts the interpretation of these studies. The present paper reviews and discusses human biobehavioral factors that can affect the measurement of circulating markers of inflammation. Keywords relevant to inflammatory biology and biobehavioral factors were searched through PubMed. Age, sex, and hormonal status, socioeconomic status, ethnicity and race, body mass index, exercise, diet, caffeine, smoking, alcohol, sleep disruption, antidepressants, aspirin, and medications for cardiovascular disease are all reviewed. A tiered set of recommendations as to whether each variable should be assessed, controlled for, or used as an exclusion criteria is provided. These recommendations provide a framework for observational and intervention studies investigating linkages between psychosocial and behavioral factors and inflammation. (C) 2009 Elsevier Inc. All rights reserved. C1 [O'Connor, Mary-Frances; Bower, Julie E.; Cho, Hyong Jin; Dimitrov, Stoyan; Hamby, Mary E.; Sloan, Erica K.; Thomas, KaMala S.; Irwin, Michael R.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA. [Bower, Julie E.; Hoyt, Michael A.; Robles, Theodore F.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Creswell, J. David] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Martin, Jennifer L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Martin, Jennifer L.] Vet Adm Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, North Hills, CA 91343 USA. RP O'Connor, MF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Cousins Ctr Psychoneuroimmunol, 300 Med Plaza,Room 3140, Los Angeles, CA 90095 USA. EM mfoconnor@mednet.ucla.edu RI Irwin, Michael/H-4870-2013; Cho, Hyong Jin/B-9934-2014 OI Irwin, Michael/0000-0002-1502-8431; Cho, Hyong Jin/0000-0002-8629-8500 FU NIA [K01 AG028404, K23 AG028452, NIMH T32-MH19925]; Cousins Center for Psychoneuroimmunology FX This work was supported by NIA Grants K01 AG028404 and K23 AG028452, NIMH T32-MH19925 and the Cousins Center for Psychoneuroimmunology. NR 174 TC 142 Z9 143 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD OCT PY 2009 VL 23 IS 7 BP 887 EP 897 DI 10.1016/j.bbi.2009.04.005 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 540PV UT WOS:000273348600003 PM 19389469 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Late effects of adjuvant systemic therapies in women diagnosed with breast cancer at a young age SO BREAST LA English DT Article DE Estrogen deprivation; Osteoporosis; Premature menopause; Breast cancer survivors; Cardiac toxicity; Neurocognitive function; Tamoxifen; Chemotherapy; Trastuzumab C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 18 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2009 VL 18 SU 3 BP S135 EP S136 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA V26HG UT WOS:000208536100024 PM 19914532 ER PT J AU Gelber, RD Gelber, S AF Gelber, Richard D. Gelber, Shari CA IBCSG BIG TI Facilitating consensus by examining patterns of treatment effects SO BREAST LA English DT Article DE Breast cancer; Adjuvant therapies; Clinical trials; Endocrine responsive; HER2-positive; Patterns of treatment effect AB Randomized clinical trials are necessary to provide reliable evidence concerning the effectiveness and safety of adjuvant therapies for breast cancer. Such trials, however, are not sufficient to provide information needed to tailor therapies to individual patients. Trials focus on testing treatments on average for heterogeneous patient populations, while attention to the specific characteristics of the disease and the patient are needed to assess the potential benefit for the individual. While 'across the board' results are useful from a population perspective, examination of patterns of treatment response during the course of follow up and for subpopulations of patients is required to make progress and solidify consensus on how to treat individual patients. For example, for several decades it has been known that the pattern of recurrence risk from time of diagnosis is different for estrogen receptor (ER)-negative and ER-positive disease. Assuming that ER status is accurately assessed and distinguishing absence of receptors from low, intermediate and high expression cohorts, one can recognize patterns of relapse risk that are early versus later during follow up. Treatments effective against ER-negative disease reduce the risk of early relapse, while those acting on ER-positive disease demonstrate effectiveness later during the course of follow up. Another example is HER2-positive disease, where a relatively high proportion of patients tend to relapse early, and treatments such as trastuzumab that reduce the risk of early relapse have demonstrated efficacy. For premenopausal patients with ER-positive disease, ovarian function suppression and endocrine effects of chemotherapy are effective to reduce the risk of late occurring relapses. Examining the influence of patient and disease-related factors on the patterns of recurrence over time and treatment responsiveness within subpopulations in multiple randomized trials can facilitate consensus on progress that has been made and identify areas for improving the care of patients with breast cancer. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gelber, Richard D.; Gelber, Shari] Frontier Sci & Technol Res Fdn Inc, IBCSG Stat Ctr, Boston, MA 02215 USA. RP Gelber, RD (reprint author), Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Mail Stop CLS 11007, Boston, MA 02115 USA. EM gelber@jimmy.harvard.edu FU Swiss Group for Clinical Cancer Research (SAKK); Frontier Science and Technology Research Foundation (FSTRF); Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council); National Cancer Institute [CA-75362]; Swedish Cancer Society; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK); Novartis; Pfizer; GSK; Roche; Merck; AstraZeneca; sanofi-aventis; Schering-Plough FX We thank the patients, investigators, nurses, data managers and all others who participate in the International Breast Cancer Study Group (IBCSG) and Breast International Group ( BIG) trials. We specifically acknowledge the contributions to the St. Gallen meeting presentation of Alan Coates, Aron Goldhirsch, Giuseppe Viale, Meredith Regan and Karen Price. Funding for IBCSG central coordination, data management, and statistics provided by Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation (FSTRF), The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council), National Cancer Institute (CA-75362), Swedish Cancer Society, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). We thank the HERA Trial Study Team, the BIG 1-98 Collaborative Group, and ALTTO Study Team for permission to present data and figures.; R.D. Gelber receives salary support for his collaboration as senior independent statistician for IBCSG and BIG clinical trials. IBCSG and BIG receive financial support for conduct of clinical trials from Novartis, Pfizer, GSK, Roche, Merck, AstraZeneca, sanofi-aventis, and Schering-Plough. S. Gelber has no funding sources to declare. NR 21 TC 8 Z9 8 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2009 VL 18 SU 3 BP S2 EP S8 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA V26HG UT WOS:000208536100001 PM 19914537 ER PT J AU Lee, LJ Harris, JR AF Lee, Larissa J. Harris, Jay R. TI Innovations in radiation therapy (RT) for breast cancer SO BREAST LA English DT Article DE Radiation therapy; Local recurrence; Local-regional recurrence; V30; V5; Intensity-modulated radiation therapy; Accelerated partial breast radiotherapy AB The EBCTCG has clearly demonstrated that the use of RT after either breast conserving surgery (BCS) or after mastectomy in node-positive patients not only reduces local recurrence (LR), but also improves long-term survival. The EBCTCG specifically found that the absolute reduction in the 5-year rate of LR was proportional to the absolute reduction in 15-year breast cancer mortality with a 4: 1 ratio. Studies from the EBCTCG have also clearly shown that when RT for breast cancer inadvertently delivers 'excessive' dose to the heart, there is an increased rate of late cardiac deaths. Over time, LR rates with RT have decreased, particularly after BCS, and this is largely due to a favorable interaction of RT with adjuvant systemic therapy. There is new information emerging about the effectiveness of RT based on newer biologic classification of breast cancer and about how the 4: 1 ratio might change in the face of increasingly effective systemic therapy and with a better understanding of the importance of biologic classification and of the competing risks of local and distant recurrence. Technical innovations in RT include the development of techniques that minimize cardiac irradiation. It is critical that CT simulation be done during which the heart should be contoured and the radiation dose-cardiac volume relationship be determined. In the EBCTCG's preliminary analysis, increased late cardiac deaths were most closely linked to mean cardiac doses >5Gy. A number of techniques are available to minimize cardiac dose both after BCS and mastectomy and these will be described. There has also been development of fractionation and treatment techniques to complete RT faster for purposes of patient convenience and to assure its optimal level of use. There are now 10-year results from a Canadian trial showing equivalent LR and cosmetic outcome with RT using the convential 25 treatments to the whole breast compared to 16 treatments using a higher dose per day. Few randomized patients, however, were treated with adjuvant chemotherapy and a boost was not used. The generalizability of the Canadian trial results to patients treated with adjuvant chemotherapy or requiring a boost is not known. For patients treated after BCS, there has been great interest in the use of accelerated partial breast irradiation (APBI), which can be accomplished using interstitial, intracavitary, external-beam or intraoperative techniques. Clinical trials are now underway to compare APBI to conventional techniques, but mature results from these trials will not be available for some time. In the U.S., ASTRO has developed a consensus statement based on an expert panel as to when APBI can be reasonably used outside of a clinical trial and this will be described. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Lee, Larissa J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Harvard Radiat Oncol Progra, Boston, MA 02115 USA. [Harris, Jay R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiat Oncol, Boston, MA 02115 USA. RP Lee, LJ (reprint author), 44 Binney St,Room 1622, Boston, MA 02115 USA. EM LLee13@Partners.org; JHarris@LROC.Harvard.edu NR 72 TC 14 Z9 16 U1 1 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2009 VL 18 SU 3 BP S103 EP S111 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA V26HG UT WOS:000208536100020 PM 19914528 ER PT J AU Mayer, EL Partridge, AH Harris, LN Gelman, RS Schumer, ST Burstein, HJ Winer, EP AF Mayer, E. L. Partridge, A. H. Harris, L. N. Gelman, R. S. Schumer, S. T. Burstein, H. J. Winer, E. P. TI Tolerability of and adherence to combination oral therapy with gefitinib and capecitabine in metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Adherence; Breast cancer; Metastatic; Capecitabine; EGFR; Gefitinib; Phase 1 ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; MULTICENTER PHASE-II; ESTROGEN-RECEPTOR; ZD1839 IRESSA; 1ST-LINE THERAPY; CLINICAL-TRIALS; PACLITAXEL; ERLOTINIB AB Purpose: This phase I study explored gefitinib (G) and capecitabine (C) in metastatic breast cancer (MBC). Methods: Sequential cohorts (n = 3) received G and escalating C on a 14 day on/7 day off schedule, with a validation cohort (n = 10) at the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was defined in cycle 1. The primary endpoint was safety; secondary endpoints included response and adherence. Results: About 19 patients were treated for a median of 5 cycles. No patients in sequential cohorts experienced DLT; C MTD was 2,000 mg/m(2)/day when paired with daily G 250 mg. In the validation cohort, four experienced serious toxicities, including diarrhea, mucositis, and palmarplantar dysesthesia. At the MTD, 6 (46%) required a C dose reduction, and 3 (23%) came off study for toxicity. One partial response was observed (8%, 95% CI 0.2-38.5%); five had stable disease > 24 weeks (26, 95% CI 9-51%). Patients missed few drug doses, with the suggestion of overadherence to therapy. Conclusions: In this phase I study of G and C in MBC, a C MTD was identified, and significant toxicity was observed. About 8% demonstrated a response, with 26% maintaining stable disease. The possibility of overadherence, as suggested in this study, may have implications for other trials of oral antineoplastic therapy. C1 [Mayer, E. L.; Partridge, A. H.; Gelman, R. S.; Burstein, H. J.; Winer, E. P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Harris, L. N.] Yale Univ, New Haven, CT USA. [Schumer, S. T.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Mayer, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Mayer 224, Boston, MA 02115 USA. EM emayer@partners.org FU NCI NIH HHS [T32 CA009172] NR 47 TC 21 Z9 22 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 OCT PY 2009 VL 117 IS 3 BP 615 EP 623 DI 10.1007/s10549-009-0366-5 PG 9 WC Oncology SC Oncology GA 495TA UT WOS:000269916700019 PM 19294501 ER PT J AU Dickinson, M Ritchie, D DeAngelo, DJ Spencer, A Ottmann, OG Fischer, T Bhalla, KN Liu, A Parker, K Scott, JW Bishton, M Prince, HM AF Dickinson, Michael Ritchie, David DeAngelo, Daniel J. Spencer, Andrew Ottmann, Oliver G. Fischer, Thomas Bhalla, Kapil N. Liu, Angela Parker, Katie Scott, Jeffrey W. Bishton, Mark Prince, H. Miles TI Preliminary evidence of disease response to the pan deacetylase inhibitor panobinostat (LBH589) in refractory Hodgkin Lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Hodgkin lymphoma; HDAC inhibitor; LBH589; panobinostat ID HISTONE; CELLS AB P>There are few treatment options for patients with Hodgkin Lymphoma (HL) who relapse after conventional therapies. Panobinostat is an orally available pan deacetylase inhibitor with evidence of activity in myeloid malignancies and cutaneous T cell lymphoma. Thirteen HL patients were treated with escalating doses of this novel agent in a phase IA/II multicentre study. A computed tomography partial response was achieved in 5/13(38%), and a metabolic response by = 1 stroke risk factor (heart failure, hypertension, age >= 65 years, diabetes, or prior TE) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden (defined as the longest total AT/AF duration on any given day during the prior 30-day period). This time-varying exposure was updated daily during follow-up and related to TE risk. Annualized TE rates were determined according to AT/AF burden subsets: zero, low (<5.5 hours [ median duration of subsets with nonzero burden]), and high (>= 5.5 hours). A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy. Patients (n=2486) had at least 30 days of device data for analysis. During a mean follow-up of 1.4 years, annualized TE risk (including transient ischemic attacks) was 1.1% for zero, 1.1% for low, and 2.4% for high burden subsets of 30-day windows. Compared with zero burden, adjusted hazard ratios (95% CIs) in the low and high burden subsets were 0.98 (0.34 to 2.82, P=0.97) and 2.20 (0.96 to 5.05, P=0.06), respectively. Conclusions-The TE rate was low compared with patients with traditional AF with similar risk profiles. The data suggest that TE risk is a quantitative function of AT/AF burden. AT/AF burden >5.5 hours on any of 30 prior days appeared to double TE risk. Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden. (Circ Arrhythmia Electrophysiol. 2009; 2: 474-480.) C1 [Glotzer, Taya V.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Daoud, Emile G.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Wyse, D. George] Libin Cardiovasc Inst Alberta, Calgary, AB, Canada. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ezekowitz, Michael D.] Lankenau Inst Med Res, Philadelphia, PA USA. [Hilker, Christopher; Miller, Clayton; Qi, Dongfeng; Ziegler, Paul D.] Medtronic Inc, Minneapolis, MN USA. RP Glotzer, TV (reprint author), Electrophysiol Associates No New Jersey, 20 Prospect Ave,Suite 701, Hackensack, NJ 07601 USA. EM TayaVG@aol.com FU Medtronic, Inc FX The TRENDS Study was sponsored by Medtronic, Inc. NR 20 TC 239 Z9 245 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD OCT PY 2009 VL 2 IS 5 BP 474 EP 480 DI 10.1161/CIRCEP.109.849638 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 508SZ UT WOS:000270957400002 PM 19843914 ER PT J AU Body, SC Collard, CD Shernan, SK Fox, AA Liu, KY Ritchie, MD Perry, TE Muehlschlegel, JD Aranki, S Donahue, BS Pretorius, M Estrada, JC Ellinor, PT Newton-Cheh, C Seidman, CE Seidman, JG Herman, DS Lichtner, P Meitinger, T Pfeufer, A Kaab, S Brown, NJ Roden, DM Darbar, D AF Body, Simon C. Collard, Charles D. Shernan, Stanton K. Fox, Amanda A. Liu, Kuang-Yu Ritchie, Marylyn D. Perry, Tjoervi E. Muehlschlegel, Jochen D. Aranki, Sary Donahue, Brian S. Pretorius, Mias Estrada, Juan-Carlos Ellinor, Patrick T. Newton-Cheh, Christopher Seidman, Christine E. Seidman, J. G. Herman, Daniel S. Lichtner, Peter Meitinger, Thomas Pfeufer, Arne Kaeaeb, Stefan Brown, Nancy J. Roden, Dan M. Darbar, Dawood TI Variation in the 4q25 Chromosomal Locus Predicts Atrial Fibrillation After Coronary Artery Bypass Graft Surgery SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE atrial fibrillation; arrhythmia; postoperative complication; heart surgery; genetics ID GENE-MUTATIONS; RISK-FACTOR; POLYMORPHISM; IDENTITY; SCN5A; SNPS AB Background-Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery. Methods and Results-Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P = 8.0 X 10(-4) to 3.4 X 10(-6)). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. Conclusions-In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons. (Circ Cardiovasc Genet. 2009;2:499-506.) C1 [Body, Simon C.; Shernan, Stanton K.; Fox, Amanda A.; Liu, Kuang-Yu; Perry, Tjoervi E.; Muehlschlegel, Jochen D.] Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Aranki, Sary] Harvard Univ, Div Cardiac Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Seidman, Christine E.] Harvard Univ, Howard Hughes Med Inst, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Collard, Charles D.] St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesia, Houston, TX USA. [Donahue, Brian S.; Pretorius, Mias] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Estrada, Juan-Carlos; Brown, Nancy J.; Roden, Dan M.; Darbar, Dawood] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Brown, Nancy J.; Roden, Dan M.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. [Ritchie, Marylyn D.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. [Seidman, Christine E.; Seidman, J. G.; Herman, Daniel S.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Seidman, J. G.] Harvard Univ, Sch Med, Partners HealthCare Ctr Genet & Genom, Boston, MA 02115 USA. [Ellinor, Patrick T.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Boston, MA USA. [Lichtner, Peter; Meitinger, Thomas; Pfeufer, Arne; Kaeaeb, Stefan] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. Tech Univ Munich, Inst Human Genet, Munich, Germany. [Kaeaeb, Stefan] Klinikum Univ Munchen Grosshadern, Med Klin, Munich, Germany. RP Body, SC (reprint author), Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM body@zeus.bwh.harvard.edu RI Ritchie, Marylyn/C-1114-2012; Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; Darbar, Dawood/C-9079-2015; Meitinger, Thomas/O-1318-2015 OI Darbar, Dawood/0000-0002-4103-5977; FU National Heart, Lung, and Blood Institute [HL65962, HL068774, HL092217] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (HL65962, HL068774, and HL092217). NR 25 TC 56 Z9 58 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2009 VL 2 IS 5 BP 499 EP U197 DI 10.1161/CIRCGENETICS.109.849075 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 574HH UT WOS:000275979500012 PM 20031626 ER PT J AU Yan, BP Clark, DJ Jaff, MR Kiernan, TJ Schainfeld, RM Lessio, S Rosenfield, K AF Yan, Bryan P. Clark, David J. Jaff, Michael R. Kiernan, Thomas J. Schainfeld, Robert M. Lessio, Sara Rosenfield, Kenneth TI Carotid Duplex Ultrasound Velocity Measurements Versus Intravascular Ultrasound in Detecting Carotid In-Stent Restenosis SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE carotid artery stenting; in-stent restenosis; duplex ultrasonography; intravascular ultrasound; restenosis ID FOLLOW-UP; ARTERY; CRITERIA; STENOSIS AB Background-Duplex ultrasonography criteria for assessing the severity of carotid artery (CA) in-stent restenosis are not well established. Methods and Results-We analyzed 39 patients (40 CAs) who underwent CA stenting with baseline and 6-month follow-up carotid duplex ultrasonography and intravascular ultrasound. Intravascular ultrasound measurements included minimum luminal diameter, percent diameter, and lumen area stenosis. Duplex ultrasonography measurements included peak systolic velocity (PSV), percentage change in PSV, end-diastolic velocity (EDV), and internal-to-common CA PSV ratio (ICA/CCA). Receiver operating characteristic curves assessed each duplex measurement to detect >= 50% diameter, >= 75% lumen area stenosis, and minimum luminal diameter < 3 mm at follow-up. At 6-month intravascular ultrasound follow-up, >= 50% diameter and >= 75% lumen area CA in-stent restenosis occurred in 20% and 25%, respectively; minimum luminal diameter < 3 cm occurred in 48%. Area under receiver operating characteristic curves for PSV, EDV, and ICA/CCA were 0.85, 0.96, and 0.89 for >= 50% diameter stenosis and 0.89, 0.93, and 0.88 for >= 75% lumen area stenosis, respectively. Optimal PSV, EDV, and ICA/CCA criteria to detect >= 50% diameter and >= 75% lumen area CA in-stent restenosis were greater compared with those for native CA. A > 98% increase in PSV had the highest specificity, whereas the combination of EDV > 41 cm/s and ICA/CCA > 2 had the highest sensitivity in detecting >= 75% lumen area CA in-stent restenosis. Conclusions-PSV, EDV, and ICA/CCA PSV ratio were good discriminators for detecting significant diameter and lumen area greater compared with those for native CA. The combination of duplex velocity criteria increases diagnostic accuracy. (Circ Cardiovasc Intervent. 2009;2:438-443.) C1 [Yan, Bryan P.; Jaff, Michael R.; Kiernan, Thomas J.; Schainfeld, Robert M.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Yan, Bryan P.] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Clark, David J.] Austin Hosp, Dept Cardiol, Melbourne, Vic 3084, Australia. [Lessio, Sara] St Elizabeths Med Ctr, Div Cardiovasc Med & Res, Boston, MA USA. RP Rosenfield, K (reprint author), Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, 55 Fruit St GRB-800, Boston, MA 02114 USA. EM krosenfield@partners.org RI Hossain, Sarah /C-7332-2009; Yan, Bryan/P-5928-2015 OI Hossain, Sarah /0000-0003-1355-0979; FU Boston Scientific Corporation FX This work was supported by Boston Scientific Corporation. NR 17 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD OCT PY 2009 VL 2 IS 5 BP 438 EP 443 DI 10.1161/CIRCINTERVENTIONS.109.857276 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575LP UT WOS:000276068800011 PM 20031754 ER PT J AU Stockl, D Sluss, PM Thienpont, LM AF Stoeckl, Dietmar Sluss, Patrick M. Thienpont, Linda M. TI Specifications for trueness and precision of a reference measurement system for serum/plasma 25-hydroxyvitamin D analysis SO CLINICA CHIMICA ACTA LA English DT Article DE Serum/plasma 25-hydroxyvitamin D2; Serum/plasma 25-hydroxyvitamin D3; Quality goals; Bias; Imprecision; Uncertainty ID TANDEM MASS-SPECTROMETRY; VITAMIN-D STATUS; REFERENCE INTERVALS; ANALYTICAL GOALS; SERUM; ASSAY; QUANTIFICATION; LABORATORIES; VALIDATION; WOMEN AB Background: The divergence in analytical quality of serum/plasma 25-hydroxy-vitamin D analysis calls for defining specifications for a reference measurement system. Methods: Fundamentally, in a reference measurement system, there should be a relationship between the analytical specifications for higher- (reference) and lower-order (routine) measurements. Therefore, when setting specifications, we started with limits for routine imprecision (CV(rou)) and bias (B(rou)) using 4 models: (1) the misclassifications in diagnosis, (2) biological variation data (reference interval (RI) and monitoring). (3) expert recommendations, and (4) state-of-the-art performance. Then, we used the derived goals to tailor those for reference measurements and certified reference materials (CRMs) for calibration by setting the limits for CV(ref) at 0.5 CV(rou), B(ref) at 0.33 B(rou), max. uncertainty (U(max)) at 0.33 B(ref). Results: The established specifications ranged between CV(rou)<= 22%, B(rou)<= 10%, CV(ref)<= 11%, B(ref)<= 3.3%, U(max) 1.1% (model 3) and CV(rou)<= 4%, B(rou)<= 2.6%, CV(ref)<= 2%, B(ref)<= 0.9%, U(max) 0.3% (model 2, monitoring). Conclusions: Model 2 (monitoring) gave the most stringent goals, model 3, the most liberal ones. Accounting for state-of-the-art performance and certification capabilities, we used model 2 (RI) to recommend achievable goals: for routine testing, CV(rou)<= 10%, B(rou)<= 5%, for reference measurements. CV(ref)<= 5%, B(ref)<= 1.7%, and for CRMs, U(max) 0.6%. (C) 2009 Elsevier B.V. All rights reserved. C1 [Stoeckl, Dietmar; Thienpont, Linda M.] Univ Ghent, Analyt Chem Lab, Fac Pharmaceut Sci, B-9000 Ghent, Belgium. [Sluss, Patrick M.] Massachusetts Gen Hosp, Clin Pathol Core Lab, Boston, MA 02114 USA. RP Thienpont, LM (reprint author), Univ Ghent, Analyt Chem Lab, Fac Pharmaceut Sci, Harelbekestr 72, B-9000 Ghent, Belgium. EM linda.thienpont@ugent.be NR 41 TC 47 Z9 47 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD OCT 1 PY 2009 VL 408 IS 1-2 BP 8 EP 13 DI 10.1016/j.cca.2009.06.027 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 502US UT WOS:000270486400002 PM 19563791 ER PT J AU Zhang, YM Schwiening, C Killeen, MJ Zhang, YH Ma, AQ Lei, M Grace, AA Huang, CLH AF Zhang, Yanmin Schwiening, Christof Killeen, Matthew J. Zhang, Yanhui Ma, Aiqun Lei, Ming Grace, Andrew A. Huang, Christopher L-H TI Pharmacological changes in cellular Ca2+homeostasis parallel initiation of atrial arrhythmogenesis in murine langendorff-perfused hearts SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE atrial arrhythmogenesis; Ca2+homeostasis; murine hearts ID CARDIAC RYANODINE RECEPTOR; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; POLYMORPHIC VENTRICULAR-TACHYCARDIA; SARCOPLASMIC-RETICULUM CALCIUM; CA2+ RELEASE; SUDDEN-DEATH; MYOCYTES; CONTRACTION; CAFFEINE; FIBRILLATION AB P>Intracellular Ca2+ overload has been associated with established atrial arrhythmogenesis. The present experiments went on to correlate acute initiation of atrial arrhythmogenesis in Langendorff-perfused mouse hearts with changes in Ca2+ homeostasis in isolated atrial myocytes following pharmacological procedures that modified the storage or release of sarcoplasmic reticular (SR) Ca2+ or inhibited entry of extracellular Ca2+. Caffeine (1 mmol/L) elicited diastolic Ca2+ waves in regularly stimulated atrial myocytes immediately following addition. This was followed by a decline in the amplitude of the evoked transients and the disappearance of such diastolic events, suggesting partial SR Ca2+ depletion. Cyclopiazonic acid (CPA; 0.15 mu mol/L) produced more gradual reductions in evoked Ca2+ transients and abolished diastolic Ca2+ events produced by the further addition of caffeine. Nifedipine (0.5 mu mol/L) produced immediate reductions in evoked Ca2+ transients. Further addition of caffeine produced an immediate increase followed by a decline in the amplitude of the evoked Ca2+ transients, without eliciting diastolic Ca2+ events. These findings correlated with changes in spontaneous and provoked atrial arrhythmogenecity in mouse isolated Langendorf-perfused hearts. Thus, caffeine was pro-arrhythmogenic immediately following but not > 5 min after application and both CPA and nifedipine pretreatment inhibited such arrhythmogenesis. Together, these findings relate acute atrial arrhythmogenesis in intact hearts to diastolic Ca2+ events in atrial myocytes that, in turn, depend upon a finite SR Ca2+ store and diastolic Ca2+ release following Ca2+-induced Ca2+ release initiated by the entry of extracellular Ca2+. C1 [Schwiening, Christof; Grace, Andrew A.; Huang, Christopher L-H] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. [Zhang, Yanmin; Zhang, Yanhui; Grace, Andrew A.; Huang, Christopher L-H] Univ Cambridge, Dept Biochem, Cambridge CB2 3EG, England. [Lei, Ming] Univ Manchester, Cardiovasc Res Grp, Sch Clin & Lab Sci, Manchester, Lancs, England. [Killeen, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Killeen, Matthew J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhang, Yanmin; Ma, Aiqun] Xi An Jiao Tong Univ, Hosp 1, Dept Cardiovasc Med, Xian 710049, Peoples R China. RP Huang, CLH (reprint author), Univ Cambridge, Physiol Lab, Downing St, Cambridge CB2 3EG, England. EM clh11@cam.ac.uk OI Lei, Ming/0000-0002-0928-341X FU British Heart Foundation; Medical Research Council; Wellcome Trust; Helen Kirkland Fund for Cardiac Research, UK; National Natural Science Foundation of China (NSFC) [30371571, 30672209]; Department for Education and Skills of the United Kingdom and the China Scholarship Council; Physiological Laboratory FX This work was supported by grants from the British Heart Foundation, the Medical Research Council, the Wellcome Trust, the Helen Kirkland Fund for Cardiac Research, UK, and the National Natural Science Foundation of China (NSFC 30371571 and 30672209). YHZ thanks the Department for Education and Skills of the United Kingdom and the China Scholarship Council for support. MJK thanks the Physiological Laboratory for the award of an Avrith Studentship. NR 41 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD OCT PY 2009 VL 36 IS 10 BP 969 EP 980 DI 10.1111/j.1440-1681.2009.05170.x PG 12 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 509FZ UT WOS:000271001700007 PM 19298534 ER PT J AU Humphreys, BD Atkins, MB AF Humphreys, Benjamin D. Atkins, Michael B. TI Rapid Development of Hypertension by Sorafenib: Toxicity or Target? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY; ANGIOGENESIS; INHIBITOR; CANCER AB Blood pressure elevation is likely a pharmacodynamic marker of VEGF signaling pathway (VSP) inhibition and could be useful for optimizing safe and effective VSP inhibitor dosing. Blood pressure rises on the first day of treatment, facilitating design and interpretation of future trials aiming to correlate blood pressure changes with clinical outcomes. (Clin Cancer Res 2009;15(19):5947-9) C1 [Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. [Humphreys, Benjamin D.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Humphreys, Benjamin D.] Dana Farber Canc Inst, Lance Armstrong Fdn Adult Survivorship Program, Boston, MA 02115 USA. [Atkins, Michael B.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. RP Atkins, MB (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, MASCO Bldg,Room 412,375 Longwood Ave, Boston, MA 02115 USA. EM matkins@bidmc.harvard.edu FU NCI NIH HHS [P50 CA101942-06A1] NR 12 TC 27 Z9 31 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 OCT 1 PY 2009 VL 15 IS 19 BP 5947 EP 5949 DI 10.1158/1078-0432.CCR-09-1717 PG 3 WC Oncology SC Oncology GA 502ZC UT WOS:000270498700002 PM 19789317 ER PT J AU Ngo, HT Azab, AK Farag, M Jia, XY Melhem, MM Runnels, J Roccaro, AM Azab, F Sacco, A Leleu, X Anderson, KC Ghobrial, IM AF Ngo, Hai T. Azab, Abdel Kareem Farag, Mena Jia, Xiaoying Melhem, Molly M. Runnels, Judith Roccaro, Aldo M. Azab, Fecla Sacco, Antonio Leleu, Xavier Anderson, Kenneth C. Ghobrial, Irene M. TI Src Tyrosine Kinase Regulates Adhesion and Chemotaxis in Waldenstrom Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID C-SRC; FAMILY KINASES; THERAPEUTIC TARGET; BONE METASTASES; CANCER CELLS; MALIGNANCIES; INHIBITION; INVASION; PATHWAY; KEY AB Purpose: Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma characterized by widespread involvement of the bone marrow. Despite different options of therapy, Waldenstrom macroglobulinemia is still incurable. Src tyrosine kinase has been shown to play a central role in the regulation of a variety of biological processes, such as cell proliferation, migration, adhesion, and survival in solid tumors. We sought to determine whether the protein tyrosine kinase Src regulates adhesion, migration, and survival in Waldenstrom macroglobulinemia. Experimental Design: We tested the expression of Src tyrosine kinase in Waldenstrom macroglobulinemia and normal cells, and the effect of the specific Src inhibitor AZD0530 on the adhesion, migration, cell cycle, and survival of a Waldenstrom macroglobulinemia cell line and patient samples. Moreover, we tested the effect of AZD0530 on cytoskeletal and cell cycle signaling in Waldenstrom macroglobulinemia. Results: We show that Src is overexpressed in Waldenstrom macroglobulinemia cells compared with control B cells, and that the use of the Src inhibitor AZD0530 led to significant inhibition of adhesion, migration, and cytoskeletal signaling induced by SDF1. Moreover, inhibition of Src activity induced G(1) cell cycle arrest; however, it had minimal effect on survival of Waldenstrom macroglobulinemia cells, and no significant effect on survival of normal cells. Conclusions: Taken together, these results delineate the role of Src kinase activity in Waldenstrom macroglobulinemia and provide the framework for future clinical trials using Src inhibitors in combination with other drugs to improve the outcome of patients with Waldenstrom macroglobulinemia. (Clin Cancer Res 2009;15(19):6035-41) C1 [Ghobrial, Irene M.] Dana Farber Canc Inst, Kirsch Lab Waldenstrom, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Kirsch Lab Waldenstrom, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 FU International Waldenstrom Macroglobulinemia Foundation; The Kirsch Laboratory for Waldenstrom; [R21CA126119-01]; [R01CA125690-01] FX R21CA126119-01, the International Waldenstrom Macroglobulinemia Foundation, The Kirsch Laboratory for Waldenstrom, and R01CA125690-01. NR 26 TC 9 Z9 9 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2009 VL 15 IS 19 BP 6035 EP 6041 DI 10.1158/1078-0432.CCR-09-0718 PG 7 WC Oncology SC Oncology GA 502ZC UT WOS:000270498700014 PM 19755386 ER PT J AU Demetri, GD Lo Russo, P MacPherson, LRJ Wang, D Morgan, JA Brunton, VG Paliwal, P Agrawal, S Voi, M Evan, TRJ AF Demetri, George D. Lo Russo, Patricia MacPherson, Lain R. J. Wang, Ding Morgan, Jeffrey A. Brunton, Valerie G. Paliwal, Prashni Agrawal, Shruti Voi, Maurizio Evan, T. R. Jeffry TI Phase I Dose-Escalation and Pharmacokinetic Study of Dasatinib in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; SRC FAMILY KINASES; PP60C-SRC PROTEIN-KINASE; GASTROINTESTINAL STROMAL TUMORS; CYTOGENETIC RESPONSES; IMATINIB-RESISTANT; TYROSINE KINASES; CELL-ADHESION; ACTIVATION; EXPRESSION AB Purpose: To determine the maximum tolerated dose, dose-limiting toxicity (DLT), and recommended phase 11 dose of dasatinib in metastatic solid tumors refractory to standard therapies or for which no effective standard therapy exists. Experimental Design: In this phase 1, open-label, dose-escalation study, patients received 35 to 160 mg of dasatinib twice daily in 28-day cycles either every 12 hours for 5 consecutive days followed by 2 nontreatment days every week (5D2) or as continuous, twice-daily (CDD) dosing. Results: Sixty-seven patients were treated (5D2, n = 33; CDD, n = 34). The maximum tolerated doses were 120 mg twice daily 5D2 and 70 mg twice daily CDD. DLTs with 160 mg 5D2 were recurrent grade 2 rash, grade 3 lethargy, and one patient with both grade 3 prolonged bleeding time and grade 3 hypocalcemia; DLTs with 120 mg twice daily CDD were grade 3 nausea, grade 3 fatigue, and one patient with both grade 3 rash and grade 2 proteinuria. The most frequent treatment-related toxicities across all doses were nausea, fatigue, lethargy, anorexia, proteinuria, and diarrhea, with infrequent hematologic toxicities. Pharmacokinetic data indicated rapid absorption, dose proportionality, and lack of drug accumulation. Although no objective tumor responses were seen, durable stable disease was observed in 16% of patients. Conclusion: Dasatinib was well tolerated in this population, with a safety profile similar to that observed previously in leukemia patients, although with much less hematologic toxicity. Limited, although encouraging, preliminary evidence of clinical activity was observed. Doses of 120 mg twice daily (5D2) or 70 mg twice daily (CDD) are recommended for further studies in patients with solid tumors. (Clin Cancer Res 2009;15(19):6232-40) C1 [Demetri, George D.; Morgan, Jeffrey A.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, George D.; Morgan, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Lo Russo, Patricia; Wang, Ding] Karmanos Canc Inst, Detroit, MI USA. [MacPherson, Lain R. J.; Evan, T. R. Jeffry] Beatson W Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Brunton, Valerie G.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Paliwal, Prashni; Agrawal, Shruti; Voi, Maurizio] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ludwig Ctr, 44 Binney St,D1212, Boston, MA 02115 USA. EM gdemetri@partners.org OI Macpherson, Iain/0000-0003-4295-8885 FU Bristol-Myers Squibb; Virginia and Daniel K. Ludwig Trust for Cancer Research; Pan-Mass Challenge of Paul's Posse and Leslie's Links; Russo Family GIST Research Fund; Gardiner-Caldwell US FX Grant support: Bristol-Myers Squibb. G.D. Demetri was supported by The Virginia and Daniel K. Ludwig Trust for Cancer Research, the Pan-Mass Challenge of Paul's Posse and Leslie's Links, and the Russo Family GIST Research Fund. Editorial and writing support was provided by Gardiner-Caldwell US and funded by Bristol-Myers Squibb. NR 43 TC 69 Z9 71 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2009 VL 15 IS 19 BP 6232 EP 6240 DI 10.1158/1078-0432.CCR-09-0224 PG 9 WC Oncology SC Oncology GA 502ZC UT WOS:000270498700036 PM 19789325 ER PT J AU James, E Podoltsev, N Salehi, E Curtis, BR Saif, MW AF James, Edward Podoltsev, Nikolai Salehi, Elahe Curtis, Brian R. Saif, Muhammad Wasif TI Oxaliplatin-Induced Immune Thrombocytopenia: Another Cumulative Dose-Dependent Side Effect? SO CLINICAL COLORECTAL CANCER LA English DT Article DE Disseminated intravascular coagulation; Drug-dependent platelet-reactive antibodies ID INDUCED HEMOLYTIC-ANEMIA; OF-THE-LITERATURE; MEDIATED THROMBOCYTOPENIA; ADJUVANT TREATMENT; COLON-CANCER; ANTIBODIES; PATIENT AB Oxaliplatin is a third-generation platinum compound that is commonly used for the treatment of colorectal cancer (CRC) both in the adjuvant and metastatic disease settings. Oxaliplatin-based chemotherapy is presently limited by cumulative dose-dependent neurotoxicity. We had previously reported on 2 patients who developed oxaliplatin-induced immune thrombocytopenia (OITP) during their tenth and seventeenth FOLFOX (5-fluorouracil/leucovorin/oxaliplatin) cycles. Herein, we report on a third patient who developed severe thrombocytopenia after 28 cycles of modified FOLFOX6 (mFOLFOX) chemotherapy. A 60-year-old white woman with metastatic CRC, who had partial sigmoidectomy and colostomy, presented with bleeding from stoma site, on cycle 28, day 1 of mFOLFOX6, 7.5 hours after completion of the oxaliplatin infusion. Laboratory data revealed marked thrombocytopenia with a nadir platelet count of zero. Due to concern for OITP, the patient's serum was sent to BloodCenter of Wisconsin, Inc. (Diagnostic Laboratories; Milwaukee, WI). Serologic testing for oxaliplatin-dependent platelet antibodies was performed using flow cytometry in the presence of various concentrations of oxaliplatin. Laboratory tests for autoimmune hemolysis and disseminated intravascular coagulation (DIC) were negative. Oxaliplatin-dependent platelet reactive antibodies were detected in the patient's serum, confirming the diagnosis of OITP. The diagnosis of OITP should be entertained in patients receiving oxaliplatin for prolonged periods of time even though there are other more common causes of thrombocytopenia in these patients, including chemotherapy-induced myelosuppression, bone marrow involvement with tumor, and DIC. C1 [Saif, Muhammad Wasif] Yale Univ, Sch Med, Sect Med Oncol, Yale Canc Ctr, New Haven, CT 06520 USA. [James, Edward] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Salehi, Elahe] Dana Farber Canc Inst, Boston, MA 02115 USA. [Curtis, Brian R.] Blood Ctr SE Wisconsin Inc, Platelet & Neutrophil Immunol Lab, Milwaukee, WI 53233 USA. RP Saif, MW (reprint author), Yale Univ, Sch Med, Sect Med Oncol, Yale Canc Ctr, 333 Cedar St,FMP 116, New Haven, CT 06520 USA. EM wasif.saif@yale.edu NR 23 TC 15 Z9 15 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD OCT PY 2009 VL 8 IS 4 BP 220 EP 224 DI 10.3816/CCC.2009.n.037 PG 5 WC Oncology SC Oncology GA 505VI UT WOS:000270726300008 PM 19822513 ER PT J AU Liu, SH Howell, P Ren, SP Fodstad, O Zhang, GY Samant, R Shevde, L Xi, YG Pannell, LK Riker, AI AF Liu, Suhu Howell, Paul Ren, Suping Fodstad, Oystein Zhang, Guangyu Samant, Rajeev Shevde, Lalita Xi, Yaguang Pannell, Lewis K. Riker, Adam I. TI Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE DKK1; DNA methylation; Tumor suppressor gene; Melanoma; WFDC1 ID TUMOR-SUPPRESSOR GENES; MALIGNANT-MELANOMA; PROSTATE-CANCER; WFDCI/PS20; DICKKOPF-1; PROMOTION; STROMA; CELLS; MODEL; PS20 AB The exact cellular and molecular mechanisms involved in melanoma tumorigenesis remain obscure. Previous gene expression profiling analyses performed upon NHEM and human melanoma samples identified WFDC1 as one of the most frequently down-regulated genes. Here we further showed that NHEM readily express WFDC1 but expression is reduced or completely lost in 80% of the patients-derived melanoma cell lines and tissue samples examined. Furthermore, we show that promoter hypermethylation accounts for the silencing of the WFDC1 gene in 20% of the melanoma cell lines examined. The over-expression of WFDC1 in two metastatic melanoma cell lines, A375 and LOX, resulted in a significant delay of tumor growth in a murine xenograft model, despite a non-significant difference in tumor cell growth in vitro. Gene expression microarray analysis and further expression validation suggests that the Dickkopf-1 (Dkk1) gene is up-regulated in WFDC1 over-expressing cell lines, suggesting that the tumor suppressive function of WFDC1 may be partially a result of up-regulated Dkk1 gene expression, which is known to be a potent inhibitor of the Wnt signaling pathway. C1 [Riker, Adam I.] Ochsner Hlth Syst, Dept Surg, Ochsner Canc Inst, New Orleans, LA 70121 USA. [Liu, Suhu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Howell, Paul; Ren, Suping; Fodstad, Oystein; Zhang, Guangyu; Samant, Rajeev; Shevde, Lalita; Xi, Yaguang; Pannell, Lewis K.] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36604 USA. [Fodstad, Oystein] Oslo Univ Hosp, Inst Canc Res, Norwegian Radium Hosp, N-0310 Oslo, Norway. [Fodstad, Oystein] Univ Oslo, Norwegian Radium Hosp, Fac Div, Fac Med, Oslo, Norway. RP Riker, AI (reprint author), Ochsner Hlth Syst, Dept Surg, Ochsner Canc Inst, 1514 Jefferson Hwy,BH 334, New Orleans, LA 70121 USA. EM suhu_liu@dfci.harvard.edu; paulhowell@usouthal.edu; sren@usouthal.edu; Oystein.Fodstad@rr-research.no; gzhang@usouthal.edu; rsamant@usouthal.edu; lsamant@usouthal.edu; xi@usouthal.edu; lpannell@usouthal.edu; ariker@ochsner.org OI Xi, Yaguang/0000-0003-3681-9352 NR 25 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 2009 VL 26 IS 7 BP 739 EP 749 DI 10.1007/s10585-009-9273-8 PG 11 WC Oncology SC Oncology GA 518VE UT WOS:000271722300015 PM 19488830 ER PT J AU Dodd, R Stangenberg, L Yoon, S Dodd, L Kirsch, D AF Dodd, Rebecca Stangenberg, Lars Yoon, Sam Dodd, Leslie Kirsch, David TI Abstracts the Metastasis Research Society-American Association for Cancer Research Conference on Metastasis Abstracts SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Dodd, Rebecca; Dodd, Leslie; Kirsch, David] Duke Univ, Med Ctr, Durham, NC USA. [Stangenberg, Lars; Yoon, Sam] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 2009 VL 26 IS 7 BP 849 EP 850 DI 10.1007/s10585-008-9214-y PG 2 WC Oncology SC Oncology GA 518VE UT WOS:000271722300028 ER PT J AU Perentes, JY Nagano, S Shaver, CM Sgroi, D Garkavstev, I Munn, LL Jain, RK Boucher, Y AF Perentes, Jean Y. Nagano, Satoshi Shaver, Christine M. Sgroi, Dennis Garkavstev, Igor Munn, Lance L. Jain, Rakesh K. Boucher, Yves TI Cancer cell-derived membrane-type I matrix metalloproteinase promotes blood vessel intravasation and distant metastasis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 2009 VL 26 IS 7 BP 868 EP 868 PG 1 WC Oncology SC Oncology GA 518VE UT WOS:000271722300079 ER PT J AU Lahdenranta, J Hagendoorn, J Padera, TP Liao, S Hoshida, T Jain, RK Fukumura, D AF Lahdenranta, Johanna Hagendoorn, Jeroen Padera, Timothy P. Liao, Shan Hoshida, Tohru Jain, Rakesh K. Fukumura, Dai TI Nitric oxide mediates lymphatic metastasis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 2009 VL 26 IS 7 BP 873 EP 873 PG 1 WC Oncology SC Oncology GA 518VE UT WOS:000271722300093 ER PT J AU Aggarwal, R Weinberg, V Small, EJ Oh, W Rushakoff, R Ryan, CJ AF Aggarwal, Rahul Weinberg, Vivian Small, Eric J. Oh, William Rushakoff, Robert Ryan, Charles J. TI The Mechanism of Action of Estrogen in Castration-Resistant Prostate Cancer: Clues From Hormone Levels SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Secondary hormonal therapy; Adrenal androgens; Castration resistance; Hormone levels ID DOSE-DIETHYLSTILBESTROL DIPHOSPHATE; PHASE-II; PC-SPES; ANTIANDROGEN WITHDRAWAL; HERBAL SUPPLEMENT; ANDROGEN; TRIAL; TESTOSTERONE; CELLS; KETOCONAZOLE AB Background: Estrogen therapy plays a role in the management of castration-resistant prostate cancer (CRPC), although the mechanism of action is not fully known. This current analysis reports the relationship of change in adrenal androgen levels and prostate-specific antigen (PSA) response in patients with CRPC treated with estrogen therapy. Patients and Methods: Hormone levels were measured for patients with CRPC treated in a multicenter phase II trial of 2 estrogen-containing compounds, the herbal supplement PC-SPES and diethylstilbestrol (DES), with known efficacy in CRPC. Patients with castrate levels of testosterone were randomized to initially receive either PC-SPES 960 mg t.i.d. or DES 3 mg/day. Levels of testosterone, dihydrotestosterone (DHT), estradiol, estrone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), and androstenedione were obtained at baseline and at 12-week intervals until disease progression. Hormone levels were obtained for 38 patients, 20 treated with PC-SPES and 18 treated with DES. Results: Significant declines between baseline and 12 weeks of treatment were observed in levels of serum testosterone (P < .001), estrone (P = .02), and DHEA (P < .001). The percent changes at 12 weeks in these hormone levels were inversely proportional to baseline values as measured by Spearman's rank correlation (testosterone:-0.41, P = .01; estrone: -0.64, P = .0001; DHEA: -0.39, P = .02). Levels of SHBG increased in almost all of the patients (97%), with a median percent increase of > 5-fold (P < .0001). Of the 38 evaluable patients, 15 (39% [95% CI, 24%-57%]) experienced a > 50% decline in PSA level. There was no significant difference between treatment groups or between responders and nonresponders in baseline distributions for any of the hormones. At follow-up, 73% of the responders had a decline in the level of DHEA-S compared with 41% of the nonresponders, resulting in a difference in the distribution of the percent change between the subsets (Mann-Whitney test: P = .03). Conversely, 64% of the responders compared with 30% of the nonresponders experienced an increase in DHT, with differing distributions of percent change (P = .02). Conclusion: Androgens decline in response to estrogen therapy. A decline in DHEA-S and a rise in DHT are both associated with a decline in PSA while patients receive estrogen therapy. C1 [Aggarwal, Rahul; Weinberg, Vivian; Small, Eric J.; Rushakoff, Robert; Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Urol Oncol Program, Dept Med, San Francisco, CA 94115 USA. [Oh, William] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Ryan, CJ (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Urol Oncol Program, Dept Med, 1600 Div St, San Francisco, CA 94115 USA. EM ryanc@medicine.ucsf.edu RI Perez , Claudio Alejandro/F-8310-2010; Oh, William/B-9163-2012 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Oh, William/0000-0001-5113-8147 NR 26 TC 9 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 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD OCT PY 2009 VL 7 IS 3 BP E71 EP E76 DI 10.3816/CGC.2009.n.027 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 528PY UT WOS:000272460100004 PM 19815485 ER PT J AU Choueiri, TK Mosquera, JM Hirsch, MS AF Choueiri, Toni K. Mosquera, Juan-Miguel Hirsch, Michelle S. TI A Case of Adult Metastatic Xp11 Translocation Renal Cell Carcinoma Treated Successfully With Sunitinib SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Alveolar soft-part sarcoma; MET; TFE3; Vascular endothelial growth factor ID FUSIONS; TFE3; MET AB Renal cell carcinomas (RCC) associated with Xp11.2 translocations (transcription factor E3 gene fusions) are rare tumors predominantly reported in children. Although only a small number of adult Xp11.2 translocation RCC cases have been described, this is likely due to the possibility of this tumor being unrecognized because of its histologic similarity to either clear cell or papillary subtypes based on hematoxylin and eosin staining. Herein, we describe the first successful case of systemic treatment of metastatic Xp11 RCC with sunitinib, a currently accepted standard of care in metastatic RCC, and attempt to elucidate potential mechanisms behind sunitinib activity in this histologic subtype. C1 [Choueiri, Toni K.] Harvard Univ, Sch Med, Lank Ctr Genitourinary Oncol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Choueiri, Toni K.; Hirsch, Michelle S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Lank Ctr Genitourinary Oncol, Brigham & Womens Hosp, 44 Binney St,Dana 1230, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu NR 13 TC 16 Z9 16 U1 1 U2 3 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 OCT PY 2009 VL 7 IS 3 BP E93 EP E94 DI 10.3816/CGC.2009.n.031 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 528PY UT WOS:000272460100008 PM 19815489 ER PT J AU Sartor, O Nakabayashi, M Taplin, ME Ross, RW Kantoff, PW Balk, SP Oh, WK AF Sartor, Oliver Nakabayashi, Mari Taplin, Mary-Ellen Ross, Robert W. Kantoff, Philip W. Balk, Steven P. Oh, William K. TI Activity of Dutasteride Plus Ketoconazole in Castration-Refractory Prostate Cancer After Progression on Ketoconazole Alone SO CLINICAL GENITOURINARY CANCER LA English DT Article DE 5-alpha reductase; Androgen receptor; Dihydrotestosterone; Prostate-specific antigen ID PHASE-II; ANDROGEN; INHIBITOR; TRIAL AB Background: Ketoconazole is a commonly used secondary hormonal therapy in castration-refractory prostate cancer (CRPC), but disease progression inevitably occurs. Both prostatic and metastatic lesions in patients with CRPC overexpress 5-alpha reductase (SRDA5) type I. We hypothesized that SRDA5 inhibition in combination with ketoconazole would mitigate progression after treatment with ketoconazole alone. Patients and Methods: A total of 10 patients with CRPC with progression after ketoconazole treatment were treated with a combination of ketoconazole plus dutasteride 0.5 mg/day, a dual SRDA5 inhibitor. Results: After dutasteride addition, 8 (80%) of the 10 patients had varying degrees of prostate-specific antigen (PSA) decline relative to baseline. Median progression-free survival after dutasteride addition was 4.9 months (range, 2.7 + to 9.8 months); no patient had a >= 50% PSA decline. Conclusion: We conclude that dutasteride added to ketoconazole at the time progression might prolong time to PSA progression in patients with CRPC. C1 [Sartor, Oliver; Nakabayashi, Mari; Taplin, Mary-Ellen; Ross, Robert W.; Kantoff, Philip W.; Oh, William K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sartor, Oliver] Tulane Canc Ctr, New Orleans, LA USA. [Balk, Steven P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Sartor, O (reprint author), 1430 Tulane Ave,Box SL-42, New Orleans, LA 70112 USA. EM osartor@tulane.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU GlaxoSmithKline FX Dr. Sartor has received research funding from and has served as a paid consultant or been on the advisory board of GlaxoSmithKline. NR 12 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 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD OCT PY 2009 VL 7 IS 3 BP E90 EP E92 DI 10.3816/CGC.2009.n.030 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 528PY UT WOS:000272460100007 PM 19815488 ER PT J AU McGovern, BH Birch, CE Bowen, MJ Reyor, LL Nagami, EH Chung, RT Kim, AY AF McGovern, Barbara H. Birch, Christopher E. Bowen, Melinda J. Reyor, Laura L. Nagami, Ellen H. Chung, Raymond T. Kim, Arthur Y. TI Improving the Diagnosis of Acute Hepatitis C Virus Infection with Expanded Viral Load Criteria SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INJECTION-DRUG USERS; T-CELL RESPONSES; HCV-RNA; PEGYLATED INTERFERON-ALPHA-2B; CLEARANCE; THERAPY; FLUCTUATIONS; MONOTHERAPY; POPULATION; ANTIBODY AB Background. The diagnosis of acute hepatitis C virus (HCV) infection is imprecise because antibody testing does not differentiate between acute and chronic infection. Although virologic features, such as viral load fluctuations and low levels of viremia, have been noted to be characteristic of acute HCV infection, these parameters have not been used for diagnosis. Methods. We validated the use of these novel parameters (ie, viral load fluctuations 11 log and HCV RNA levels <100,000 IU/mL) in a cohort of acute HCV seroconverters. We then applied standard diagnostic criteria for acute HCV infection in a cohort of high-risk injection drug users entering prison with suspected acute HCV infection (n = 37). We subsequently assessed whether these novel virologic parameters, measured serially over a 10-week period, could enhance the diagnosis of acute infection. Results. Low-level viremia and viral load fluctuations were highly prevalent in our cohort of acute seroconverters (81% and 86%, respectively), whereas low-level viremia occurred in only 13% of control patients with chronic infection. With use of standard criteria, 37 inmates received a diagnosis of acute HCV infection. Among the 35 patients with HCV RNA detectable at baseline, we found low-level viremia to be highly prevalent (n = 27; 77%); among patients with a minimum of 2 HCV RNA samples, we demonstrated viral fluctuations in more than one-third (n = 9; 36%). Conclusions. The diagnosis of acute infection in HCV-seropositive patients is strengthened by the use of virologic parameters that are uncommon in chronic disease. Viral load fluctuations and low levels of HCV RNA should be incorporated into standard diagnostic criteria. C1 [McGovern, Barbara H.] Lemuel Shattuck Hosp, Div Infect Dis, Jamaica Plain, MA 02130 USA. [McGovern, Barbara H.] Massachusetts Gen Hosp, Tufts Med Sch, Boston, MA 02114 USA. [Reyor, Laura L.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chung, Raymond T.; Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA USA. [Birch, Christopher E.; Nagami, Ellen H.; Kim, Arthur Y.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Birch, Christopher E.; Bowen, Melinda J.; Reyor, Laura L.; Nagami, Ellen H.; Kim, Arthur Y.] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA USA. [Birch, Christopher E.; Bowen, Melinda J.; Reyor, Laura L.; Nagami, Ellen H.; Kim, Arthur Y.] Harvard Univ, Charlestown, MA USA. [Bowen, Melinda J.] Univ Massachusetts, Sch Med, Worcester, MA USA. RP McGovern, BH (reprint author), Lemuel Shattuck Hosp, Div Infect Dis, 170 Morton St, Jamaica Plain, MA 02130 USA. EM bmcgovern@tuftsmedicalcenter.org FU National Institutes of Health and National Institute of Allergy and Infectious Diseases [U19 AI066345, K23 AI054379]; Harvard University Center for AIDS Research [P30 AI060354] FX National Institutes of Health and National Institute of Allergy and Infectious Diseases (Hepatitis C Cooperative Center U19 AI066345; K23 AI054379 to A. Y. K.; Harvard University Center for AIDS Research P30 AI060354). NR 40 TC 48 Z9 50 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 2009 VL 49 IS 7 BP 1051 EP 1060 DI 10.1086/605561 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 492PX UT WOS:000269672300010 PM 19725787 ER PT J AU Ivers, LC Cullen, KA Freedberg, KA Block, S Coates, J Webb, P AF Ivers, Louise C. Cullen, Kimberly A. Freedberg, Kenneth A. Block, Steven Coates, Jennifer Webb, Patrick TI HIV/AIDS, Undernutrition, and Food Insecurity SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; RESOURCE-POOR SETTINGS; HIV-INFECTION; CHILDHOOD MALNUTRITION; SOUTH-AFRICA; WEIGHT-LOSS; NUTRITION; ADHERENCE; AIDS AB Despite tremendous advances in care for human immunodeficiency virus (HIV) infection and increased funding for treatment, morbidity and mortality due to HIV/AIDS in developing countries remains unacceptably high. A major contributing factor is that 1800 million people remain chronically undernourished globally, and the HIV epidemic largely overlaps with populations already experiencing low diet quality and quantity. Here, we present an updated review of the relationship between HIV infection, nutritional deficiencies, and food insecurity and consider efforts to interrupt this cycle at a programmatic level. As HIV infection progresses, it causes a catabolic state and increased susceptibility to other infections, which are compounded by a lack of caloric and other nutrient intake, leading to progressive worsening of malnutrition. Despite calls from national and international organizations to integrate HIV and nutritional programs, data are lacking on how such programs can be effectively implemented in resource-poor settings, on the optimum content and duration of nutritional support, and on ideal target recipients. C1 [Ivers, Louise C.] Partners In Hlth, Boston, MA USA. [Ivers, Louise C.; Cullen, Kimberly A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ivers, Louise C.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Block, Steven; Coates, Jennifer; Webb, Patrick] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Block, Steven] Tufts Univ, Fletcher Sch Law & Diplomacy, Boston, MA 02111 USA. RP Ivers, LC (reprint author), Div Global Hlth Equ, FXB Bldg,7th Fl,651 Huntington Ave, Boston, MA 02115 USA. EM livers@pih.org FU National Institute of Allergy and Infectious Diseases [K23 AI063998, K24 AI062476]; Harvard Center for AIDS Research [P30 AI060354-02S1] FX National Institute of Allergy and Infectious Diseases (grant K23 AI063998 to L. C. I. and grant K24 AI062476 to K. A. F.) and the Harvard Center for AIDS Research (grant P30 AI060354-02S1). NR 107 TC 68 Z9 69 U1 0 U2 19 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 2009 VL 49 IS 7 BP 1096 EP 1102 DI 10.1086/605573 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 492PX UT WOS:000269672300019 PM 19725790 ER PT J AU Boyajian, R AF Boyajian, Richard TI Survivorship Treatment Summary and Care Plan: Tools to Address Patient Safety Issues? SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Editorial Material ID INFORMATION; CANCER C1 Dana Farber Canc Inst, Lance Armstrong Fdn Adult Survivorship Clin, Boston, MA 02115 USA. RP Boyajian, R (reprint author), Dana Farber Canc Inst, Lance Armstrong Fdn Adult Survivorship Clin, Boston, MA 02115 USA. EM richard_boyajian@dfci.harvard.edu NR 9 TC 3 Z9 3 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD OCT PY 2009 VL 13 IS 5 BP 584 EP 586 DI 10.1188/09.CJON.584-586 PG 3 WC Oncology; Nursing SC Oncology; Nursing GA 506JM UT WOS:000270771100020 PM 19793715 ER PT J AU Kleeman, CR Levine, BS Felsenfeld, AJ AF Kleeman, Charles R. Levine, Barton S. Felsenfeld, Arnold J. TI Fuller Albright: The Consummate Clinical Investigator SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID OSTEITIS FIBROSA CYSTICA; PARATHYROID-GLANDS; HYPERPARATHYROIDISM; PHYSIOLOGY; OSTEOPOROSIS; THERAPY; HYPOPARATHYROIDISM; COMPLICATIONS; DIAGNOSIS C1 Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Arnold.Felsenfeld@va.gov NR 36 TC 2 Z9 2 U1 0 U2 1 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 OCT PY 2009 VL 4 IS 10 BP 1541 EP 1546 DI 10.2215/CJN.03030509 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 504LI UT WOS:000270617900001 PM 19808238 ER PT J AU Strahilevitz, J Jacoby, GA Hooper, DC Robicsek, A AF Strahilevitz, Jacob Jacoby, George A. Hooper, David C. Robicsek, Ari TI Plasmid-Mediated Quinolone Resistance: a Multifaceted Threat SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID SPECTRUM-BETA-LACTAMASE; PENTAPEPTIDE REPEAT PROTEINS; COMPLETE NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI STRAINS; GRAM-NEGATIVE BACTERIA; MULTIDRUG EFFLUX PUMP; WATER TREATMENT-PLANT; 16S RIBOSOMAL-RNA; FLUOROQUINOLONE-MODIFYING ENZYME; INTENSIVE-CARE UNITS AB Although plasmid-mediated quinolone resistance (PMQR) was thought not to exist before its discovery in 1998, the past decade has seen an explosion of research characterizing this phenomenon. The best-described form of PMQR is determined by the qnr group of genes. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins. These proteins reduce susceptibility to quinolones by protecting the complex of DNA and DNA gyrase or topoisomerase IV enzymes from the inhibitory effect of quinolones. Two additional PMQR mechanisms were recently described. aac(6')-Ib-cr encodes a variant aminoglycoside acetyltransferase with two amino acid alterations allowing it to inactivate ciprofloxacin through the acetylation of its piperazinyl substituent. oqxAB and qepA encode efflux pumps that extrude quinolones. All of these genes determine relatively small increases in the MICs of quinolones, but these changes are sufficient to facilitate the selection of mutants with higher levels of resistance. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. Several factors suggest their importance in this process, including their increasing ubiquity, their association with other resistance elements, and their emergence simultaneous with the expansion of clinical quinolone resistance. Of concern, these genes are not yet being taken into account in resistance screening by clinical microbiology laboratories. C1 [Strahilevitz, Jacob] Hadassah Hebrew Univ, Dept Clin Microbiol & Infect Dis, IL-91120 Jerusalem, Israel. [Jacoby, George A.] Lahey Clin Fdn, Burlington, MA 01805 USA. [Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Robicsek, Ari] Univ Chicago, Pritzker Sch Med, NorthShore Univ HealthSyst, Dept Med, Evanston, IL 60201 USA. RP Strahilevitz, J (reprint author), Hadassah Hebrew Univ, Dept Clin Microbiol & Infect Dis, IL-91120 Jerusalem, Israel. EM jstrahilevitz@hadassah.org.il FU NIAID NIH HHS [R01 AI057576, AI43312, AI57576, R01 AI043312] NR 226 TC 391 Z9 423 U1 7 U2 61 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2009 VL 22 IS 4 BP 664 EP + DI 10.1128/CMR.00016-09 PG 27 WC Microbiology SC Microbiology GA 505RG UT WOS:000270711700008 PM 19822894 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI The Contribution of Clinical Trials in Psychiatry: A Basic Science of Clinical Care SO CNS SPECTRUMS LA English DT Editorial Material ID EVIDENCE-BASED MEDICINE; CRISIS C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD OCT PY 2009 VL 14 IS 10 BP 528 EP 529 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 512SF UT WOS:000271270100001 PM 20095364 ER PT J AU Micco, JA Ehrenreich, JT AF Micco, Jamie A. Ehrenreich, Jill T. TI Validity and Specificity of the Children's Automatic Thoughts Scale in Clinically Anxious and Non-clinical Children SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Children; Anxiety; Cognition; Self-report ID PSYCHOMETRIC PROPERTIES; COGNITIVE SPECIFICITY; DEPRESSION SCALE; ANXIETY; ADOLESCENTS; SAMPLE AB The present study is a preliminary examination of the internal, criterion, and convergent validity of the Children's Automatic Thoughts Scale (CATS; Schniering and Rapee 2002), a developmentally sensitive measure of cognitions associated with childhood internalizing and externalizing disorders, among clinically anxious and non-clinical children. Participants included 40 children (ages 7-14) with a clinical anxiety disorder and 40 non-clinical children with no prior anxiety disorder diagnosis. Results supported the internal consistency and criterion validity of the measure. In addition, controlling for age, sex, and clinical status, convergent validity was largely supported, with the Physical Threat subscale correlating with self-report of generalized anxiety and separation anxiety, and the Social Threat and Personal Failure subscales correlating with self-report of social anxiety and major depression. Limitations and suggestions for further research on the utility of the CATS are discussed. C1 [Micco, Jamie A.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Cambridge, MA 02138 USA. [Ehrenreich, Jill T.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Micco, JA (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM jmicco@partners.org NR 17 TC 8 Z9 9 U1 0 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD OCT PY 2009 VL 33 IS 5 BP 532 EP 536 DI 10.1007/s10608-009-9230-5 PG 5 WC Psychology, Clinical SC Psychology GA 488TH UT WOS:000269372500009 ER PT J AU Reuter, M Wolter, FE Shenton, M Niethammer, M AF Reuter, Martin Wolter, Franz-Erich Shenton, Martha Niethammer, Marc TI Laplace-Beltrami eigenvalues and topological features of eigenfunctions for statistical shape analysis SO COMPUTER-AIDED DESIGN LA English DT Article; Proceedings Paper CT Workshop on New Advances in Shape Analysis and Geometric Modeling CY OCT, 2007 CL Leibniz Univ, Hannover, GERMANY HO Leibniz Univ DE Laplace-Beltrami spectra; Eigenvalues; Eigenfunctions; Nodal domains; Morse-Smale complex; Reeb graph; Brain structure; Caudate nucleus; Schizotypal personality disorder ID SURFACES; SPECTRA; LOCI AB This paper proposes the use of the surface-based Laplace-Beltrami and the volumetric Laplace eigenvalues and eigenfunctions as shape descriptors for the comparison and analysis of shapes. These spectral measures are isometry invariant and therefore allow for shape comparisons with minimal shape pre-processing. In particular, no registration, mapping, or remeshing is necessary. The discriminatory power of the 2D surface and 3D solid methods is demonstrated on a population of female caudate nuclei (a subcortical gray matter structure of the brain, involved in memory function, emotion processing, and learning) of normal control subjects and of subjects with schizotypal personality disorder. The behavior and properties of the Laplace-Beltrami eigenvalues and eigenfunctions are discussed extensively for both the Dirichlet and Neumann boundary condition showing advantages of the Neumann vs. the Dirichlet spectra in 3D. Furthermore, topological analyses employing the Morse-Smale complex (on the surfaces) and the Reeb graph (in the solids) are performed on selected eigenfunctions, yielding shape descriptors, that are capable of localizing geometric properties and detecting shape differences by indirectly registering topological features such as critical points, level sets and integral lines of the gradient field across subjects. The use of these topological features of the Laplace-Beltrami eigenfunctions in 2D and 3D for statistical shape analysis is novel. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Reuter, Martin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Wolter, Franz-Erich] Leibniz Univ Hannover, Inst Mensch Maschine Kommunikat, Hannover, Germany. [Shenton, Martha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Reuter, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Niethammer, Marc] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA. [Niethammer, Marc] Univ N Carolina, Sch Med, Biomed Res Imaging Ctr, Chapel Hill, NC USA. RP Reuter, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. EM reuter@mit.edu RI Reuter, Martin/B-3456-2010; Wolter , Franz - Erich /B-1672-2014; OI Reuter, Martin/0000-0002-2665-9693; Wolter, Franz - Erich/0000-0002-2293-5494 FU NIBIB NIH HHS [U54 EB005149, U54 EB005149-050012]; NIMH NIH HHS [K05 MH070047, K05 MH070047-06, R01 MH050740, R01 MH050740-14] NR 44 TC 61 Z9 65 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0010-4485 EI 1879-2685 J9 COMPUT AIDED DESIGN JI Comput.-Aided Des. PD OCT PY 2009 VL 41 IS 10 SI SI BP 739 EP 755 DI 10.1016/j.cad.2009.02.007 PG 17 WC Computer Science, Software Engineering SC Computer Science GA 504QO UT WOS:000270632300006 PM 20161035 ER PT J AU Grissom, CK Morris, AH Lanken, PN Ancukiewicz, M Orme, JF Schoenfeld, DA Thompson, BT AF Grissom, Colin K. Morris, Alan H. Lanken, Paul N. Ancukiewicz, Marek Orme, James F. Schoenfeld, David A. Thompson, B. Taylor CA Natl Heart Lung Blood Inst Acute R TI Association of physical examination with pulmonary artery catheter parameters in acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; physical examination; pulmonary artery catheterization; superior vena cava oxygen saturation; mixed venous oxygen saturation ID VENOUS OXYGEN-SATURATION; CRITICALLY ILL PATIENTS; RANDOMIZED CONTROLLED-TRIAL; SURVIVING SEPSIS CAMPAIGN; SEPTIC SHOCK; MANAGEMENT; THERAPY; GUIDELINES; OUTCOMES; PATIENT AB Objective, To correlate physical examination findings, central venous pressure, fluid output and central venous oxygen saturation with pulmonary artery catheter parameters. Design: Retrospective study. Setting: Data from the multicenter Fluid and Catheter Treatment Trial of the National Institutes of Health Acute Respiratory Distress Syndrome Network. Patients: Five hundred thirteen patients with acute lung injury randomized to treatment with a pulmonary artery catheter. Interventions: Correlation of physical examination findings (capillary refill time >2 secs, knee mottling, or cool extremities), central venous pressure, fluid output, and central venous oxygen saturation with parameters from a pulmonary artery catheter. Measurements: We determined association of baseline physical examination findings and on-study parameters of central venous pressure and central venous oxygen saturation with cardiac index <2.5 L/min/m(2) and mixed venous oxygen saturation <60%. We determined correlation of baseline central venous oxygen saturation and mixed venous oxygen saturation and predictive value of a low central venous oxygen saturation for a low mixed venous oxygen saturation. Measurements and Main Results: Prevalence of cardiac index <2.5 and mixed venous oxygen saturation <60% was 8.1% and 15.5%, respectively. Baseline presence of all three physical examination findings had low sensitivity (12% and 8%), high specificity (98% and 99%), low positive predictive value (40% and 56%), but high negative predictive value (93% and 86%) for cardiac index <2.5 and mixed venous oxygen saturation <60%, respectively. Central venous oxygen saturation <70% predicted a mixed venous oxygen saturation <60% with a sensitivity 84%, specificity 70%, positive predictive value 31%, and negative predictive value of 96%. Low cardiac index correlated with cool extremities, high central venous pressure, and low 24-hr fluid output; and low mixed venous oxygen saturation correlated with knee mottling and high central venous pressure, but these correlations were not found to be clinically useful. Conclusions: In this subset of patients with acute lung injury, there is a high prior probability that cardiac index and mixed venous oxygen saturation are normal and physical examination findings of ineffective circulation are not useful for predicting low cardiac index or mixed venous oxygen saturation. Central venous oxygen saturation >= 70% does not accurately predict mixed venous oxygen saturation <60%, but a central venous oxygen saturation :70% may be useful to exclude mixed venous oxygen saturation <60%. (Crit Care Med 2009; 37:2720-2726) C1 [Grissom, Colin K.; Morris, Alan H.; Orme, James F.] Intermt Med Ctr, Salt Lake City, UT USA. [Grissom, Colin K.; Morris, Alan H.; Orme, James F.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Lanken, Paul N.] Univ Penn, Philadelphia, PA 19104 USA. [Ancukiewicz, Marek; Schoenfeld, David A.; Thompson, B. Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grissom, CK (reprint author), Intermt Med Ctr, Salt Lake City, UT USA. EM colin.grissom@imail.org FU NHLBI NIH HHS [N01-HR-16146-54, N01-HR46054-64, U01 HL123009, N01HR46062, N01 HR016146, N01HR46054] NR 29 TC 31 Z9 31 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 OCT PY 2009 VL 37 IS 10 BP 2720 EP 2726 DI 10.1097/CCM.0b013e3181a59532 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 499OU UT WOS:000270234700006 PM 19885995 ER PT J AU Kaneki, M Shinozaki, S Chang, K Shimizu, N AF Kaneki, Masao Shinozaki, Shohei Chang, Kyungho Shimizu, Nobuyuki TI Could insulin sensitization be used as an alternative to intensive insulin therapy to improve the survival of intensive care unit patients with stress-induced hyperglycemia? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE intensive insulin therapy; insulin sensitization; stress-induced hyperglycemia ID CRITICALLY-ILL PATIENTS; INDEPENDENT PREDICTOR; GLYCEMIC VARIABILITY; GLUCOSE CONTROL; MORTALITY; RESISTANCE; METAANALYSIS; SIRT1 C1 [Kaneki, Masao; Shinozaki, Shohei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. [Chang, Kyungho] Univ Tokyo, Grad Sch Med, Dept Anesthesia, Tokyo, Japan. [Chang, Kyungho] Univ Tokyo, Grad Sch Med, Pain Relief Ctr, Tokyo, Japan. [Shimizu, Nobuyuki] Univ Tokyo, Dept Gastrointestinal Surg, Grad Sch Med, Tokyo, Japan. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. FU NIDDK NIH HHS [R01 DK058127] NR 18 TC 2 Z9 2 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 OCT PY 2009 VL 37 IS 10 BP 2856 EP 2858 DI 10.1097/CCM.0b013e3181aff7bb PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 499OU UT WOS:000270234700033 PM 19865018 ER PT J AU Hirsch, AE Jha, RM Yoo, AJ Growney, ML Hirsch, JA AF Hirsch, A. E. Jha, R. M. Yoo, A. J. Growney, M. L. Hirsch, J. A. TI The use of vertebral augmentation for vertebral compression fractures in elderly cancer patients: an institutional experience SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Meeting Abstract CT 10th Meeting of the International-Society-of-the-Geriatric-Oncology CY OCT 15-17, 2009 CL Berlin, GERMANY SP Int Soc Geriat Oncol C1 [Hirsch, A. E.; Jha, R. M.; Yoo, A. J.; Growney, M. L.; Hirsch, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, A. E.] Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD OCT PY 2009 VL 72 SU 1 BP S56 EP S56 DI 10.1016/S1040-8428(09)70145-3 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 520EW UT WOS:000271824100144 ER PT J AU McCleary, NJ AF McCleary, N. Jackson TI EGFR, K-Ras, BRAF testing in the elderly: same as in younger patients? SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Meeting Abstract CT 10th Meeting of the International-Society-of-the-Geriatric-Oncology CY OCT 15-17, 2009 CL Berlin, GERMANY SP Int Soc Geriat Oncol C1 [McCleary, N. Jackson] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD OCT PY 2009 VL 72 SU 1 BP S9 EP S9 DI 10.1016/S1040-8428(09)70008-3 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 520EW UT WOS:000271824100007 ER PT J AU Sugawara, M Geffner, DL Martinez, D Hershman, JM AF Sugawara, Masahiro Geffner, David L. Martinez, Dorothy Hershman, Jerome M. TI Novel treatment of medullary thyroid cancer SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE indomethacin; medullary thyroid cancer; target chemotherapy; treatment of medullary thyroid cancer ID PHASE-II TRIAL; CARCINOMA-CELLS; CARCINOEMBRYONIC-ANTIGEN; VALPROIC ACID; TUMOR-GROWTH; APOPTOSIS; CAPECITABINE; THERAPY; INTERLEUKIN-12; INDOMETHACIN AB Purpose of review Metastatic medullary thyroid cancer (MTC) is an incurable disease once metastasis becomes unresectable. Many therapeutic drugs and methods have been tried to circumvent this difficulty. We review currently published treatments and hope for future developments of more effective treatment methods. Recent findings Motesanib, vandetanib, axitinib (tyrosine kinase inhibitors), and XL184 (multikinase inhibitor) have been shown to achieve partial response or stable disease state of metastatic MTC. Sunitinib and sorafenib, currently available tyrosine kinase inhibitors, can also be tried for patients with MTC. However, these medications are not curative and do not improve survival rate. Only carcinoembryonic antigen-I-131-iodine-based radioimmunotherapy improved survival of a subset of patients with a very aggressive type of MTC. Drugs currently available for possible use of MTC treatment include bortezomib (proteasome inhibitor), valproic acid (histone deacetylase inhibitor), capecitabine (5-fluorouracil prodrug), and indomethacin (NSAID), although clinical studies have yet to be done. Cardiac natriuretic hormones and an extract of the plant Cautleya gracilis are new agents to be studied for MTC. Summary Kinase inhibitors are the first drugs showing some efficacy in MTC. To improve survival, unconventional drugs or other therapies with or without kinase inhibitors need to be considered. C1 [Sugawara, Masahiro; Hershman, Jerome M.] Univ Calif Los Angeles, Endocrinol & Diabet Div, Greater Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA 90073 USA. [Geffner, David L.; Martinez, Dorothy] Univ Calif Los Angeles, Div Endocrinol, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Sugawara, M (reprint author), Univ Calif Los Angeles, Endocrinol & Diabet Div, Greater Los Angeles VA Med Ctr, Dept Med, 111M,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM msugawar@ucla.edu FU VA Merit Review Research Grant FX The present publication was supported by VA Merit Review Research Grant (to M. S.). NR 48 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD OCT PY 2009 VL 16 IS 5 BP 367 EP 372 DI 10.1097/MED.0b013e3283304f0c PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691CF UT WOS:000285057200007 PM 19633548 ER PT J AU Bei, M AF Bei, Marianna TI Molecular genetics of tooth development SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID PLURIPOTENT STEM-CELLS; MOUSE INCISORS; IN-VIVO; DIFFERENTIATION; MORPHOGENESIS; GENERATION; TEETH; COMPARTMENT; ORIGIN; NUMBER AB Organogenesis depends upon a well-ordered series of inductive events involving coordination of molecular pathways that regulate the generation and patterning of specific cell types. Key questions in organogenesis involve the identification of the molecular mechanisms by which proteins interact to organize distinct pattern formation and cell fate determination. Tooth development is an excellent context for investigating this complex problem because of the wealth of information emerging from studies of model organisms and human mutations. Since there are no obvious sources of stem cells in adult human teeth, any attempt to create teeth de novo will probably require the reprogramming of other cell types. Thus, the fundamental understanding of the control mechanisms. responsible for normal tooth patterning in the embryo will help us understand cell fate specificity and may provide valuable information towards tooth organ regeneration. C1 [Bei, Marianna] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA. [Bei, Marianna] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Bei, Marianna] Forsyth Inst, Ctr Regenerat Dev Biol, Boston, MA 02115 USA. RP Bei, M (reprint author), Massachusetts Gen Hosp, Dept Surg, 114 16th St, Boston, MA 02129 USA. EM mbei@partners.org FU NIH [RO3 DE 018415, RO1 DE 19226]; Harvard Skin Disease Research Center; Harvard Medical School FX This work was supported by grants from the NIH (RO3 DE 018415; RO1 DE 19226), Harvard Skin Disease Research Center (Pilot Fund Award) and Harvard Medical School (Milton Fund Award) to NIB. We thank Dr Intan Ruspita for her help in preparing the tables and figure. NR 42 TC 70 Z9 73 U1 1 U2 16 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 2009 VL 19 IS 5 BP 504 EP 510 DI 10.1016/j.gde.2009.09.002 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 527JR UT WOS:000272363800012 PM 19875280 ER PT J AU Barczak, AK Hung, DT AF Barczak, Amy K. Hung, Deborah T. TI Productive steps toward an antimicrobial targeting virulence SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID SMALL-MOLECULE INHIBITOR; GRAM-NEGATIVE BACTERIA; RING-FUSED 2-PYRIDONES; STAPHYLOCOCCUS-AUREUS; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; ANTIBIOTIC PROPERTIES; BIOFILM FORMATION; PILUS BIOGENESIS; SORTASE-A AB Targeting virulence factors has gained increasing attention as a potential approach to new antibiotics. Small molecule inhibitors of virulence have been shown to change the course of disease in whole organism infection models. Recently, key advances in the field include the identification of novel targets within cell signaling pathways, a new class of anti-virulence compounds that target bacterial defenses against host immunity, and a growing body of in vivo data to support the general approach of anti-virulence therapies. Additionally, there has been a distinct trend toward developing broader spectrum anti-virulence compounds, in particular agents with activity against diverse Gram-negative organisms. Herein we provide an update on the status of the field with a focus on recent advancements. C1 [Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Barczak, Amy K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hung, Deborah T.] Harvard Univ, Dept Microbiol & Mol Genet, Sch Med, Boston, MA 02114 USA. [Hung, Deborah T.] 7 Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA. [Hung, Deborah T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Hung, DT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM dhung@broad.mit.edu FU NIAID NIH HHS [T32 AI007061, K08 AI060708-04, K08 AI060708] NR 49 TC 49 Z9 51 U1 0 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD OCT PY 2009 VL 12 IS 5 BP 490 EP 496 DI 10.1016/j.mib.2009.06.012 PG 7 WC Microbiology SC Microbiology GA 516SP UT WOS:000271563200004 PM 19631578 ER PT J AU Fischbach, MA AF Fischbach, Michael A. TI Antibiotics from microbes: converging to kill SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID BIOSYNTHETIC GENE-CLUSTER; ISOPENICILLIN-N SYNTHASE; COMPLETE GENOME SEQUENCE; CLAVULANIC ACID; LIPID-II; POSTTRANSLATIONAL MODIFICATIONS; STREPTOMYCES-CLAVULIGERUS; BETA-LACTAMASES; BACTERIA; EVOLUTION AB As genetically encoded small molecules, antibiotics are phenotypes that have resulted from mutation and natural selection. Advances in genetics, biochemistry, and bioinformatics have connected hundreds of antibiotics to the gene clusters that encode them, allowing these molecules to be analyzed using the tools of evolutionary biology. This review surveys examples of convergent evolution from microbially produced antibiotics, including the convergence of distinct gene clusters on similar phenotypes and the merger of distinct gene clusters into a single functional unit. Examining antibiotics through an evolutionary lens highlights the versatility of biosynthetic pathways, reveals lessons for combating antibiotic resistance, and provides an entry point for studying the natural roles of these natural products. C1 [Fischbach, Michael A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fischbach, Michael A.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Fischbach, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM fischbach@fischbachgroup.org FU Department of Molecular Biology; Center for Computational and Integrative Biology at Massachusetts General Hospital FX I am indebted to Laura Brown, Jon Clardy, and Christopher Walsh for helpful discussions and comments on the manuscript, and to the Department of Molecular Biology and the Center for Computational and Integrative Biology at Massachusetts General Hospital for research funding and support. NR 69 TC 29 Z9 29 U1 1 U2 23 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD OCT PY 2009 VL 12 IS 5 BP 520 EP 527 DI 10.1016/j.mib.2009.07.002 PG 8 WC Microbiology SC Microbiology GA 516SP UT WOS:000271563200008 PM 19695947 ER PT J AU Millington, TM Madsen, JC AF Millington, Timothy M. Madsen, Joren C. TI Innate immunity in heart transplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE complement; heart transplant; innate immunity; natural killer cells; Toll-like receptors ID NATURAL-KILLER-CELLS; ISCHEMIA-REPERFUSION INJURY; CARDIAC ALLOGRAFT-REJECTION; TOLL-LIKE RECEPTOR; NK CELLS; INFLAMMATORY RESPONSE; MYOCARDIAL-ISCHEMIA; ENDOGENOUS LIGAND; PERIPHERAL-BLOOD; COMPLEMENT AB Purpose of review Cardiac transplantation is the treatment of choice for end-stage heart failure, but its efficacy is limited by the development of cardiac allograft vasculopathy (CAV). Although the adaptive immune system is efficiently suppressed by conventional drugs, the innate immune system is largely unaffected. The innate response may contribute both to stimulation of the adaptive response and to the future development of CAV. Recent findings Stimulation of Toll-like receptors by endogenous ligands released in response to ischemia/reperfusion causes an inflammatory milieu favorable to graft rejection and unfavorable to tolerance. New evidence suggests that natural killer cells have previously unknown memory-like features and are capable of graft rejection. Their role in rejecting the cardiac allograft has previously been underestimated. Complement deposition may also contribute to acute cellular rejection and CAV. Summary The innate immune system is an important but neglected component of allograft rejection. Drugs that target Toll-like receptors, natural killer cells and complement may play an important role in preventing CAV and achieving tolerance to cardiac allografts. C1 [Millington, Timothy M.; Madsen, Joren C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL018646, P01 HL018646-300013, R01 HL071932, R01 HL071932-02] NR 34 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD OCT PY 2009 VL 14 IS 5 BP 571 EP 576 DI 10.1097/MOT.0b013e32832e7158 PG 6 WC Transplantation SC Transplantation GA 506IJ UT WOS:000270768200021 PM 19542889 ER PT J AU Chan, O Murooka, T Fish, E AF Chan, Olivia Murooka, Thomas Fish, Eleanor TI The role of CCL5/RANTES in regulating nutrient receptor traffiking, metabolism and protein expression in activated T cells SO CYTOKINE LA English DT Meeting Abstract CT Tri-Society Annual Conference of the International-Cytokine-Society/International-Society-of-Interferon-and-C ytokine-Research/Society-of-Leukocyte-Biology CY OCT 17-21, 2009 CL Lisbon, PORTUGAL SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res, Soc Leukocyte Biol C1 [Chan, Olivia; Murooka, Thomas; Fish, Eleanor] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A1, Canada. [Murooka, Thomas] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Fish, Eleanor] Toronto Gen Hosp, Div Cellular Mol Biol, Res Inst, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2009 VL 48 IS 1-2 BP 55 EP 55 DI 10.1016/j.cyto.2009.07.165 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 507LN UT WOS:000270855100173 ER PT J AU Pott, GB Beard, KS Regulski, M Shapiro, L AF Pott, Gregory B. Beard, K. Scott Regulski, Matthew Shapiro, Leland TI Activated collagen accelerates wound repair and modulates cytokine production in whole blood and PBMC cultures SO CYTOKINE LA English DT Meeting Abstract CT Tri-Society Annual Conference of the International-Cytokine-Society/International-Society-of-Interferon-and-C ytokine-Research/Society-of-Leukocyte-Biology CY OCT 17-21, 2009 CL Lisbon, PORTUGAL SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res, Soc Leukocyte Biol C1 [Pott, Gregory B.; Beard, K. Scott; Shapiro, Leland] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Pott, Gregory B.; Beard, K. Scott; Shapiro, Leland] Univ Colorado Denver, Dept Med, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2009 VL 48 IS 1-2 BP 93 EP 93 DI 10.1016/j.cyto.2009.07.390 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 507LN UT WOS:000270855100325 ER PT J AU Raquel, H Moita, C Hacohen, N Moita, L AF Raquel, Helena Moita, Catarina Hacohen, Nir Moita, Luis TI Identification of genes involved in unconventional protein secretion pathways SO CYTOKINE LA English DT Meeting Abstract CT Tri-Society Annual Conference of the International-Cytokine-Society/International-Society-of-Interferon-and-C ytokine-Research/Society-of-Leukocyte-Biology CY OCT 17-21, 2009 CL Lisbon, PORTUGAL SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res, Soc Leukocyte Biol C1 [Raquel, Helena; Moita, Catarina; Moita, Luis] Univ Lisbon, Inst Mol Med, P-1699 Lisbon, Portugal. [Hacohen, Nir] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Moita, Luis/L-1296-2013; OI Moita, Luis/0000-0003-0707-315X; Raquel, Helena/0000-0001-6008-6852; Ferreira Moita, Catarina/0000-0002-9910-2343 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2009 VL 48 IS 1-2 BP 118 EP 118 DI 10.1016/j.cyto.2009.07.499 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 507LN UT WOS:000270855100428 ER PT J AU Garrett, WS Glimcher, LH AF Garrett, Wendy S. Glimcher, Laurie H. TI T-bet-/- RAG2-/- ulcerative colitis: The role of T-bet as a peacekeeper of host-commensal relationships SO CYTOKINE LA English DT Review DE T-bet; Colitis; Dendritic cells; Intestine; Commensal ID INFLAMMATORY BOWEL DISEASES; CELL-DEPENDENT COLITIS; INTESTINAL INFLAMMATION; SYMBIOTIC BACTERIA; DENDRITIC CELLS; HELICOBACTER-HEPATICUS; INNATE; INTERLEUKIN-23; MUCOSAL; MICE AB Inflammatory bowel disease is a disease that reflects a disequilibrium in host-commensal homeostasis. T-bet-/- x RAG2-/- deficient mice develop a spontaneous juvenile ulcerative colitis resulting from a pro-inflammatory response to the commensal microbiota that is dendritic cell and TNF-alpha driven [schematized in Fig. 1]. The TRUC (T-bet-/- RAG2-/- ulcerative colitis) model is discussed in the broader context of the adaptive and innate immune mechanisms that regulate host-commensal relationships within the intestine. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Garrett, Wendy S.; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Garrett, Wendy S.; Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM wendy_garrett@dfci.harvard.edu; lglimche@hsph.harvard.edu FU NCI NIH HHS [R01 CA112663, R01 CA112663-09, T32 CA009172] NR 43 TC 9 Z9 10 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2009 VL 48 IS 1-2 BP 144 EP 147 DI 10.1016/j.cyto.2009.07.007 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 507LN UT WOS:000270855100509 PM 19666230 ER PT J AU Corradini, E Babitt, JL Lin, HY AF Corradini, Elena Babitt, Jodie L. Lin, Herbert Y. TI The RGM/DRAGON family of BMP co-receptors SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE BMP; Receptors; RGM; DRAGON; HJV ID REPULSIVE GUIDANCE MOLECULE; MORPHOGENETIC PROTEIN CORECEPTOR; REGULATES HEPCIDIN EXPRESSION; CENTRAL-NERVOUS-SYSTEM; MOUSE VISUAL-SYSTEM; JUVENILE HEMOCHROMATOSIS; IRON-METABOLISM; GENE-EXPRESSION; MATRIPTASE-2 TMPRSS6; SOLUBLE HEMOJUVELIN AB The BMP signaling pathway controls a number of cell processes during development and in adult tissues. At the cellular level, ligands of the BMP family act by binding a hetero-tetrameric signaling complex, composed of two type I and two type If receptors. BMP ligands make use of a limited number of receptors, which in turn activate a common signal transduction cascade at the intracellular level. A complex regulatory network is required in order to activate the signaling cascade at proper times and locations, and to generate specific downstream effects in the appropriate cellular context. One such regulatory mechanism is the repulsive guidance molecule (RGM) family of BMP co-receptors. This article reviews the current knowledge regarding the structure, regulation, and function of RGMs, focusing on known and potential roles of RGMs in physiology and pathophysiology. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Corradini, Elena; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol,Div Nephrol,Ctr Syst Biol, Boston, MA 02472 USA. RP Lin, HY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol,Div Nephrol,Ctr Syst Biol, 185 Cambridge St,Room CPZN 8216, Boston, MA 02472 USA. EM lin.herbert@mgh.harvard.edu RI Corradini, Elena/O-4167-2016 OI Corradini, Elena/0000-0001-9477-2164 FU Massachusetts Biomedical Research Council; MGH Executive Committee on Research; Associazione Modenese per le Malattie del Fegato; National Institutes of Health [K08 DK-075846, RO1 DK-069533, RO1 DK-071837]; National Kidney Foundation; Massachusetts General Hospital FX HYL is supported in part by NIH grants RO1 DK-069533 and RO1 DK-071837. NR 102 TC 46 Z9 49 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD OCT-DEC PY 2009 VL 20 IS 5-6 BP 389 EP 398 DI 10.1016/j.cytogfr.2009.10.008 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 539EF UT WOS:000273235700006 PM 19897400 ER PT J AU Hong, CC Yu, PB AF Hong, Charles C. Yu, Paul B. TI Applications of small molecule BMP inhibitors in physiology and disease SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE High throughput screen; Bone morphogenetic protein; TGF-beta; Anemia; Hepcidin; Cardiomyocyte; Embryonic stem cell; Fibrodysplasia ossificans progressiva; Bone mineral density ID EMBRYONIC STEM-CELLS; ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR-BETA; HETEROTOPIC OSSIFICATION; HEPCIDIN EXPRESSION; IRON OVERLOAD; CARDIOMYOCYTE DIFFERENTIATION; SMAD1/5 PHOSPHORYLATION; FUNCTIONAL-ANALYSIS; MESODERM INDUCTION AB Bone morphogenetic proteins (BMPs) provide critical signals for determining cell fate, specifying gastrulation, embryonic patterning, organogenesis, and the remodeling of diverse tissues. Recent work has suggested that in addition to coordinating pivotal events in development, BMPs may also regulate certain homeostatic physiological processes independently of effects on cell growth or differentiation. We recently described the identification of dorsomorphin, a small molecule inhibitor of BMP type I receptors which inhibits BMP signaling in preference to TGF-beta, Activin, and other ligands of the TGF-beta family. We describe a number of strategies using dorsomorphin and its derivatives as probes to assess the physiologic roles of BMP signaling. We also discuss several potential applications for small molecule BMP inhibitors, including stem cell manipulation, and the therapeutic modification of bone remodeling, heterotopic ossification, and iron homeostasis. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Yu, Paul B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Yu, Paul B.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Yu, Paul B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hong, Charles C.] Vanderbilt Univ, Div Cardiovasc Med, Sch Med, Nashville, TN 37232 USA. [Hong, Charles C.] Vanderbilt Univ, Ctr Inherited Heart Dis, Sch Med, Dept Med, Nashville, TN 37232 USA. [Hong, Charles C.] Vanderbilt Univ, Ctr Inherited Heart Dis, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. RP Yu, PB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Their 512,50 Blossom St, Boston, MA 02114 USA. EM pbyu@partners.org RI Hong, Charles/C-9989-2010; OI Yu, Paul/0000-0003-2145-4944 FU NIH [K08HL081535, K08HL079943]; GSK Cardiovascular Research and Education Foundation; Veterans Health Administration; Center for Research in Fibrodysplasia Ossificans and Related Disorders; Pulmonary Hypertension Association; Massachusetts Technology Transfer Center; Howard Hughes Medical Institute; Harvard Stem Cell Institute FX The authors appreciate the critical comments and review of this manuscript by Drs. Nobuhiro Kamiya and Yuji Mishina, and additional input from Drs. Greg Cuny, Randall Peterson, Kenneth Bloch, Xiao-Fan Wang and Irwin Liu. This work was supported by funding from the NIH grants K08HL081535 (CCH) and K08HL079943 (PBY), the GSK Cardiovascular Research and Education Foundation (CCH and PBY), the Veterans Health Administration (CCH), the Center for Research in Fibrodysplasia Ossificans and Related Disorders (CCH), the Pulmonary Hypertension Association (PBY), the Massachusetts Technology Transfer Center (PBY), the Howard Hughes Medical Institute (PBY), and the Harvard Stem Cell Institute (PBY). NR 72 TC 55 Z9 58 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD OCT-DEC PY 2009 VL 20 IS 5-6 SI SI BP 409 EP 418 DI 10.1016/j.cytogfr.2009.10.021 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 539EF UT WOS:000273235700008 PM 19914855 ER PT J AU Schulz, TJ Tseng, YH AF Schulz, Tim J. Tseng, Yu-Hua TI Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE Bone morphogenetic proteins; Adipose tissue; Energy metabolism ID BROWN ADIPOSE-TISSUE; DIET-INDUCED OBESITY; MESENCHYMAL PRECURSOR CELLS; MARROW STROMAL CELLS; TGF-BETA SUPERFAMILY; EMBRYONIC STEM-CELLS; ADIPOCYTE DIFFERENTIATION; WHITE ADIPOSE; PREADIPOCYTE DIFFERENTIATION; TRANSCRIPTIONAL CONTROL AB Bone morphogenetic proteins (BMPs) regulate many processes in embryonic development as well as in the maintenance of normal tissue function later in adult life. However, the role of this family of proteins in formation of adipose tissue has been underappreciated in the field of developmental biology. With the growing epidemic of obesity, improved knowledge of adipocyte development and function is urgently needed. Recently, there have been significant advances in understanding the role of different members of the BMP superfamily in control of adipocyte differentiation and systemic energy homeostasis. This review summarizes recent progress in understanding how BMPs specify adipose cell fate in stem/progenitor cells and their potential role in energy metabolism. We propose that BMPs provide instructive signals for adipose cell fate determination and regulate adipocyte function. These findings have opened up exciting opportunities for developing new therapeutic approaches for the treatment of obesity and its many associated metabolic disorders. (C) 2009 Elsevier Ltd. All rights reserved C1 [Tseng, Yu-Hua] Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Tseng, YH (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM yu-hua.tseng@joslin.harvard.edu RI Schulz, Tim/F-4842-2013 OI Schulz, Tim/0000-0002-8413-3972 FU German Research Foundation; NIH [DK077097]; Eli Lilly Research Foundation; Harvard Stem Cell Institute; Harvard Catalyst/Harvard Clinical and Translational Science Center FX We thank A.M. Cypess and K.L. Townsend for a critical reading of the manuscript. T.J.S. is supported by a fellowship from the German Research Foundation. This work was supported in part by an NIH R01 grant DK077097, and research grants from the Eli Lilly Research Foundation, the Harvard Stem Cell Institute, and the Harvard Catalyst/Harvard Clinical and Translational Science Center (to Y.-H.T.). NR 108 TC 68 Z9 72 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD OCT-DEC PY 2009 VL 20 IS 5-6 BP 523 EP 531 DI 10.1016/j.cytogfr.2009.10.019 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 539EF UT WOS:000273235700022 PM 19896888 ER PT J AU Lawrence, AE Liverant, GI Rosellini, AJ Brown, TA AF Lawrence, Amy E. Liverant, Gabrielle I. Rosellini, Anthony J. Brown, Timothy A. TI GENERALIZED ANXIETY DISORDER WITHIN THE COURSE OF MAJOR DEPRESSIVE DISORDER: EXAMINING THE UTILITY OF THE DSM-IV HIERARCHY RULE SO DEPRESSION AND ANXIETY LA English DT Article DE anxiety; classification; comorbidity; depression; diagnosis ID PARTLY DIFFERENT ENVIRONMENTS; STATE WORRY QUESTIONNAIRE; PRIMARY-CARE PATIENTS; MOOD DISORDERS; PANIC DISORDER; PSYCHOMETRIC PROPERTIES; COMORBID CONDITIONS; CO-MORBIDITY; BEHAVIORAL ACTIVATION; NEGATIVE AFFECT AB Background: The current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) specifies that generalized anxiety disorder (GAD) should not be diagnosed if it occurs exclusively during an episode of a major depressive disorder (MDD) or another mood disorder. This hierarchy rule was intended to promote diagnostic parsimony, but may result in the loss of important clinical information. The goal of this study was to compare individuals with MDD, comorbid MDD and GAD, and GAD within the course of MDD at intake and 12-month follow-up on self-report measures, clinician ratings, and rates of comorbidity. Methods: Participants were divided into three diagnostic groups: MDD without GAD (n = 124), comorbid MDD and GAD (n = 59), and GAD within the course of MDD (n = 166). All the participants completed a semi-structured clinical interview and self-report measures assessing psychopathology, temperament, and functional impairment. A subset of the total sample completed a follow-up assessment of 12 months postintake. Results: Individuals with comorbid MDD and GAD and GAD within the course of MDD reported more psychopathology, negative affect, and functional impairment at intake than individuals with MDD only. The presence of GAD at intake, however, did not differentially predict symptom severity, functional impairment, or the presence of comorbidity at 12-month follow-up. Conclusions: Cross-sectional findings indicate that individuals with GAD within the course of MDD experience levels of psychopathology, functional impairment, and comorbidity similar to those found in individuals with comorbid GAD and MDD. Preliminary longitudinal findings, however, suggest that the presence of GAD in patients with MDD does not have prognostic significance. Depression and Anxiety 26:909-916, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Lawrence, Amy E.; Rosellini, Anthony J.; Brown, Timothy A.] Boston Univ, Ctr Anxiety & Related Disorders, Dept Clin Psychol, Boston, MA 02215 USA. [Liverant, Gabrielle I.] VA Boston Healthcare Syst, Boston, MA USA. RP Lawrence, AE (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, Dept Clin Psychol, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM alawrenc@bu.edu NR 47 TC 12 Z9 14 U1 11 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2009 VL 26 IS 10 BP 909 EP 916 DI 10.1002/da.20607 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 503ZR UT WOS:000270582000006 PM 19798759 ER PT J AU Bauman, WA AF Bauman, William A. TI The potential metabolic consequences of cerebral palsy: inferences from the general population and persons with spinal cord injury SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the American-Academy-for-Cerebral-Palsy-and-Developmental-Medicine CY SEP 17-20, 2008 CL Atlanta, GA SP Amer Acad Cerebral Palsy & Dev Med ID HIGH-DENSITY-LIPOPROTEIN; DEPENDENT DIABETES-MELLITUS; CORONARY-HEART-DISEASE; CHOLESTEROL-EDUCATION-PROGRAM; CHRONIC ELECTRICAL-STIMULATION; RESIDUAL NEUROLOGICAL DEFICIT; MOTOR FUNCTION CLASSIFICATION; CARDIOVASCULAR RISK-FACTORS; INVIVO INSULIN RESISTANCE; PHYSICAL-ACTIVITY LEVEL AB The metabolic consequences of cerebral palsy (CP) have not been reported. The observations and suggestions presented in this article are based on our current knowledge of physiology in the general population and on information on the known metabolic consequences of disability in persons with spinal cord injury. Because of pain, fatigue, and other secondary consequences of CP, adolescents with CP who are ambulatory may become less physically active with age. This phenomenon would be expected to be associated with deconditioning and adverse changes in body composition including atrophy of muscles and an absolute or relative increase in adiposity. Insulin resistance, hyperinsulinemia, and associated adverse metabolic changes may develop. In an unfavorable metabolic milieu, the ability of the pancreas to compensate for mild elevations of circulating glucose may diminish. The combination of reduced fitness and conventional risk factors for cardiovascular disease would be expected to increase the risk for coronary heart disease (CHD); however, there has been no assessment of the risk factors for CHD in adults with CP. Once subgroups with modifiable risk factors for cardiovascular disease have been identified, risk factors for CHD should be aggressively treated, according to current standards of care. C1 [Bauman, William A.] James J Peters Vet Affairs Med Ctr, Spinal Cord Injury & Med Serv, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY USA. [Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Spinal Cord Injury & Med Serv, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY USA. EM william.bauman@va.gov NR 136 TC 13 Z9 13 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 EI 1469-8749 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD OCT PY 2009 VL 51 SU 4 BP 64 EP 78 DI 10.1111/j.1469-8749.2009.03430.x PG 15 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 490WS UT WOS:000269539400010 PM 19740212 ER PT J AU Tanaka, J Qiang, L Banks, AS Welch, CL Matsumoto, M Kitamura, T Ido-Kitamura, Y DePinho, RA Accili, D AF Tanaka, Jun Qiang, Li Banks, Alexander S. Welch, Carrie L. Matsumoto, Michihiro Kitamura, Tadahiro Ido-Kitamura, Yukari DePinho, Ronald A. Accili, Domenico TI Foxo1 Links Hyperglycemia to LDL Oxidation and Endothelial Nitric Oxide Synthase Dysfunction in Vascular Endothelial Cells SO DIABETES LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; TRANSCRIPTION FACTOR FOXO1; E-DEFICIENT MICE; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; KNOCKOUT MICE; L-ARGININE; ATHEROSCLEROSIS; PEROXYNITRITE; PROTEIN AB OBJECTIVE-Atherosclerotic cardiovascular disease is the leading cause of death among people with diabetes. Generation of oxidized LDLs and reduced nitric oxide (NO) availability because of endothelial NO synthase (eNOS) dysfunction are critical events in atherosclerotic plaque formation. Biochemical mechanism leading from hyperglycemia to oxLDL formation and eNOS dysfunction is unknown. RESEARCH DESIGN AND METHODS-We show that glucose, acting through oxidative stress, activates the transcription factor Foxol in vascular endothelial cells. RESULTS-Foxol promotes inducible NOS (iNOS)-dependent NO-peroxynitrite generation, which leads in turn to LDL oxidation and eNOS dysfunction. We demonstrate that Foxol gain-of-function mimics the effects of hyperglycemia on this process, whereas conditional Foxol knockout in vascular endothelial cells prevents it. CONCLUSIONS-The findings reveal a hitherto unsuspected role of the endothelial iNOS-NO-peroxynitrite pathway in lipid peroxidation and eNOS dysfunction and suggest that Foxol activation in response to hyperglycemia brings about proatherogenic changes in vascular endothelial cell function. Diabetes 58: 2344-2354, 2009 C1 [Tanaka, Jun; Qiang, Li; Banks, Alexander S.; Welch, Carrie L.; Matsumoto, Michihiro; Accili, Domenico] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10027 USA. [Kitamura, Tadahiro; Ido-Kitamura, Yukari] Gunma Univ, Inst Mol & Cellular Regulat, Metab Signal Res Ctr, Maebashi, Gunma, Japan. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Dept Med Oncol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. RP Accili, D (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10027 USA. EM da230@columbia.edu RI Qiang, Li/C-9560-2012; Banks, Alexander/B-4832-2012 OI Banks, Alexander/0000-0003-1787-6925 FU National Institutes of Health [P01-HL-87123, P30-DK-63608]; Columbia Diabetes & Endocrinology Research Center FX This work was supported by National Institutes of Health Grants P01-HL-87123 and P30-DK-63608 (Columbia Diabetes & Endocrinology Research Center). NR 50 TC 37 Z9 40 U1 1 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 OCT PY 2009 VL 58 IS 10 BP 2344 EP 2354 DI 10.2337/db09-0167 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 506LL UT WOS:000270776200022 PM 19584310 ER PT J AU Hivert, MF Grant, RW Warner, AS Meigs, JB Shrader, P AF Hivert, Marie-France Grant, Richard W. Warner, Ana Sofia Meigs, James B. Shrader, Peter TI Diabetes Risk Perception and Intention to Adopt Healthy Lifestyles Among Primary Care Patients SO DIABETES CARE LA English DT Article ID BEHAVIOR; PREVENTION; JUDGMENTS; MELLITUS AB OBJECTIVE - To examine perceived risk of developing diabetes in primary care patients. RESEARCH DESIGN AND METHODS - we recruited 150 nondiabetic primary care patients. We made standard clinical measurements, collected fasting blood samples, and used the validated Risk Perception Survey for Developing Diabetes questionnaire. RESULTS - Patients with high perceived risk were more likely than those with low perceived risk to have a family history of diabetes (68 vs. 18%; P < 0.0001) and to have metabolic syndrome (53 vs. 35%; P = 0.04). However, patients with high perceived risk were not more likely to have intentions to adopt healthier lifestyle in the coming year (high 26.0% vs. low 29.2%; P = 0.69). CONCLUSIONS - Primary care patients with higher perceived risk of diabetes were at higher actual risk but did not express greater intention to adopt healthier lifestyles. Aspects of health behavior theory other than perceived risk need to be explored to help target efforts in the primary prevention of diabetes. C1 [Hivert, Marie-France; Grant, Richard W.; Warner, Ana Sofia; Meigs, James B.; Shrader, Peter] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Hivert, Marie-France; Grant, Richard W.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Grant, Richard/0000-0002-6164-8025 FU Massachusetts General Hospital Clinical Research Program; American Diabetes Association Career Development Award; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K24 DK080140, K23 DK067452]; Centre de Recherche Medicale de l'Universite de Sherbrooke; Canadian Institute of Health Research Fellowships Health Professional Award FX This study was funded by the Massachusetts General Hospital Clinical Research Program, an American Diabetes Association Career Development Award (to J.B.M.), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant K24 DK080140 (to J.B.M.). M.F.H. was supported by the Centre de Recherche Medicale de l'Universite de Sherbrooke and a Canadian Institute of Health Research Fellowships Health Professional Award. R.W.G. was supported by NIDDK Grant K23 DK067452. NR 11 TC 30 Z9 30 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2009 VL 32 IS 10 BP 1820 EP 1822 DI 10.2337/dc09-0720 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509HE UT WOS:000271004900010 PM 19592631 ER PT J AU de Boer, IH Katz, R Cao, JJ Fried, LF Kestenbaum, B Mukamal, K Rifkin, DE Sarnak, MJ Shlipak, MG Siscovick, DS AF de Boer, Ian H. Katz, Ronit Cao, Jie J. Fried, Linda F. Kestenbaum, Bryan Mukamal, Ken Rifkin, Dena E. Sarnak, Mark J. Shlipak, Michael G. Siscovick, David S. TI Cystatin C, Albuminuria, and Mortality Among Older Adults With Diabetes SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ALL-CAUSE MORTALITY; KIDNEY-FUNCTION; CARDIOVASCULAR MORTALITY; SERUM CREATININE; FUNCTION DECLINE; ELDERLY PERSONS; RISK-FACTORS; DISEASE; PROTEINURIA AB OBJECTIVE - Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health Outcomes among individuals with diabetes. joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population. RESEARCH DESIGN AND METHODS - This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples. RESULTS - Of 691 participants, 378 died over 1.0 years of follow-up. Cystatin C-estimated GFR <60 ml/min per 1.73 m(2), creatinine-based estimated GFR <60 ml/min per 1.73 m(2), and urine ACR >= 30 mg/g were each associated with increased mortality risk with hazard ratios of 1.73 (95% CI 1.37-2.18), 1.54 (1.21-1.97), and 1.73 (1.39-2.17), respectively, adjusting for age, sex, race, diabetes duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol, lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent heart failure. Cystatin C-estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C-estimated GFR predicted mortality more strongly than creatinine-based estimated GFR. CONCLUSIONS - Albuminuria and impaired GFR were independent, additive risk factors for mortality among older adults with diabetes. These Findings support current recommendations to regularly assess both albuminuria and GFR in the clinical care of patients with diabetes a focus on interventions to prevent or treat CVD in the presence of albuminuria, impaired GFR, or both; and further consideration of cystatin C use in clinical care. C1 [de Boer, Ian H.; Katz, Ronit; Kestenbaum, Bryan; Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA. [Cao, Jie J.] NHLBI, Bethesda, MD 20892 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Mukamal, Ken] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rifkin, Dena E.; Sarnak, Mark J.] Tufts Med Ctr, Boston, MA USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP de Boer, IH (reprint author), Univ Washington, Seattle, WA 98195 USA. EM deboer@u.washington.edu FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01-HL-080295]; National Institute of Neurological Disorders and Stroke; National Institutes of Health [R01-AG-027002, 1KL2-RR-025015-01] FX The research reported in this article was supported by the National Heart, Lung, and Blood Institute (contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133 and Grant U01-HL-080295), with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support came from National Institutes of Health grants R01-AG-027002 and 1KL2-RR-025015-01. NR 25 TC 51 Z9 51 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2009 VL 32 IS 10 BP 1833 EP 1838 DI 10.2337/dc09-0191 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509HE UT WOS:000271004900013 PM 19587367 ER PT J AU Rosenstock, J Yang, F Reusch, J Stewart, M Bush, M AF Rosenstock, Julio Yang, Fred Reusch, Jane Stewart, Murray Bush, Mark CA Albiglutide Study Grp TI Potential of Albiglutide, a Long-Acting GLP-1 Receptor Agonist, in Type 2 Diabetes A randomized controlled trial exploring weekly, biweekly, and monthly dosing SO DIABETES CARE LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; BLOOD-GLUCOSE CONTROL; EXENATIDE EXENDIN-4; GLYCEMIC CONTROL; TREATED PATIENTS; HOMEOSTASIS; METFORMIN; SULFONYLUREA; OUTCOMES; PROTEIN AB OBJECTIVE - To evaluate the efficacy, safety, and tolerability of incremental doses of albiglutide, a long-acting glucagon-like peptide-1 receptor agonist, administered with three dosing schedules in patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapy. RESEARCH DESIGN AND METHODS - In this randomized multicenter double-blind parallel-group study, 356 type 2 diabetic subjects With similar mean baseline characteristics (age 54 years, diabetes duration 4.9 years, BMI 32.1 kg/m(2), AlC 8.0%) received subcutaneous placebo or albiglutide (weekly [4, 15, or 30 mg], biweekly [15, 30, or 50 mg], or monthly [50 or 100 mg]) or exenatide twice daily as an open-label active reference (per labeling in metformin subjects only) over 16 weeks followed by an 11-week washout period. The main outcome measure was change from baseline AlC of albiglutide groups versus placebo at week 16. RESULTS - Dose-dependent reductions in AlC were observed within all albiglutide schedules. Mean AlC was similarly reduced from baseline by albiglutide 30 mg weekly, 50 mg biweekly (every 2 weeks), and 100 mg monthly (-0.87, -0.79, and -0.87%, respectively) versus placebo (-0.17%, P < 0.004) and exenatide (-0.54%). Weight loss (-1.1 to -1.7 kg) was observed with these three albiglutide doses with no significant between-group effects. The incidence of gastrointestinal adverse events in subjects receiving albiglutide 30 mg weekly was less than that observed for the highest biweekly and monthly doses of albiglutide or exenatide. CONCLUSIONS - Weekly albiglutide administration significantly improved glycemic control and elicited weight loss in type 2 diabetic patients, with a favorable safety and tolerability profile. C1 [Rosenstock, Julio] Dallas Diabet & Endocrine Ctr Med City, Dallas, TX USA. [Reusch, Jane] Univ Colorado Denver AMC, Div Endocrinol Metab & Diabet, Denver, CO USA. [Reusch, Jane] Denver Vet Affairs Med Ctr, Denver, CO USA. [Bush, Mark] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Yang, Fred; Stewart, Murray] GlaxoSmithKline Inc, King Of Prussia, PA USA. RP Rosenstock, J (reprint author), Dallas Diabet & Endocrine Ctr Med City, Dallas, TX USA. EM juliorosenstock@dallasdiabetes.com FU GlaxoSmithKline FX This study was sponsored by GlaxoSmithKline, Middlesex, U.K. J.Ro. has received research grants and consulting honoraria for serving on scientific advisory boards from GlaxoSmithKline. J.Re. has received research grants from and acted as a consultant for GlaxoSmithKline. M.B., F.Y., and M.S. are employees/Stockholders of GlaxoSmithKline. No other Potential conflicts of interest relevant to this article were reported. NR 25 TC 120 Z9 125 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2009 VL 32 IS 10 BP 1880 EP 1886 DI 10.2337/dc09-0366 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509HE UT WOS:000271004900022 PM 19592625 ER PT J AU Hivert, MF Sun, Q Shrader, P Mantzoros, CS Meigs, JB Hu, FB AF Hivert, M. F. Sun, Q. Shrader, P. Mantzoros, C. S. Meigs, J. B. Hu, F. B. TI Circulating IL-18 and the risk of type 2 diabetes in women SO DIABETOLOGIA LA English DT Article DE Adipokines; Adiponectin; Case-control study; C-reactive protein; Cytokine; Diabetes incidence; Interleukin-18; Resistin ID HUMAN ADIPOSE-TISSUE; INSULIN-RESISTANCE; PLASMA INTERLEUKIN-18; METABOLIC SYNDROME; HUMAN ADIPOCYTES; LIFE-STYLE; TNF-ALPHA; OBESITY; ADIPONECTIN; BIOMARKERS AB The pathophysiology of type 2 diabetes involves pro-inflammatory pathways. We tested the hypothesis that IL-18 predicts future diabetes cases. We used a nested case-control design based in the Nurses' Health Study. Baseline blood samples were collected between 1989 and 1990. Questionnaires to assess body weight, lifestyle (physical activity, diet, smoking) and diabetes diagnosis were sent out and assessed biennially (follow-up until 2002). Cases (n = 1,012) were defined as women developing type 2 diabetes at least 1 year after blood sampling. Control women (n = 1,081) were matched to cases by age, date of blood draw, fasting status and race. We calculated the RR (95% CI) of type 2 diabetes in quintiles of IL-18 using conditional logistic regression with the first quintile as referent; adjustments included matching factors, diabetes risk factors, BMI, adipokine levels (adiponectin, resistin) and inflammatory proteins (C-reactive protein, tumour necrosis factor receptor 2 (TNF alpha-R2) and IL-6). Higher IL-18 levels were associated with increased risk of developing diabetes, even after adjustment for matching factors and multiple diabetes risk factors: being in the highest quintile of IL-18 was associated with a RR of 1.75 (1.41-2.18) for diabetes relative to the first quintile (p < 0.0001 for trend). Significant trends in association were still observed after adjustment for BMI (RR 1.44 [1.15-1.80], p < 0.0001 for trend) and adiponectin levels (RR 1.28 [1.02-1.60], p = 0.006 for trend). Further adjustment for inflammatory markers in a sub-sample did not significantly change the results. Elevated IL-18 levels are associated with higher risk of diabetes. This association is independent of usual risk factors, including BMI and adipokine levels. C1 [Sun, Q.; Hu, F. B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sun, Q.; Hu, F. B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hivert, M. F.; Shrader, P.; Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Hivert, M. F.; Meigs, J. B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Mantzoros, C. S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Hu, F. B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM fhu@hsph.harvard.edu FU NIH [DK58845, DK58785, DK79929, DK 081913]; Centre de Recherche Medicale de l'Universite de Sherbrooke (CRMUS); Canadian Institute of Health Research (CHIR); American Diabetes Association; NIDDK [K24 DK080140]; GlaxoSmithKline; Sanofi-aventis; Beth Israel Deaconess Medical Center FX The data used in this report were taken from the Nurses' Health Study, which is located in the Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School. The National Institutes of Health provided funding for this study (NIH grant DK58845). The funding source played no role in the collection, analysis or interpretation of the data, or the decision to submit the manuscript for publication. M. F. Hivert was supported by the Centre de Recherche Medicale de l'Universite de Sherbrooke (CRMUS) and a Canadian Institute of Health Research (CHIR) Fellowships Health Professional Award. J.B. Meigs was supported by a Career Development Award from the American Diabetes Association and by NIDDK K24 DK080140, and currently has research grants from GlaxoSmithKline and sanofi-aventis, as well as consulting agreements with sanofi-aventis, GlaxoSmithKline, Interleukin Genetics, Kalypsis and Outcomes Science. C. S. Mantzoros is supported by NIH grants DK58785, DK79929, DK 081913 and DK58845, and by a discretionary grant from Beth Israel Deaconess Medical Center. The authors would like to thank J. Chamberland for his contribution to the IL-18 assays in C. S. Mantzoros's laboratory. NR 31 TC 26 Z9 29 U1 1 U2 2 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 OCT PY 2009 VL 52 IS 10 BP 2101 EP 2108 DI 10.1007/s00125-009-1455-z PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 494VT UT WOS:000269848100016 PM 19669125 ER PT J AU Kennealey, PT Saidi, RF Markmann, JF Ko, DSC Kawai, T Yeh, H AF Kennealey, Peter T. Saidi, Reza F. Markmann, James F. Ko, Dicken S. C. Kawai, Tatsuo Yeh, Heidi TI Duplicated Inferior Vena Cava-Something to Consider in the Evaluation of a Living-Donor Renal Transplant SO DIALYSIS & TRANSPLANTATION LA English DT Article ID NEPHRECTOMY; ANOMALIES; VEIN AB Congenital anomalies of the inferior vena cava are rare and usually of no clinical significance. The presence of a duplicated inferior vena cava (D-IVC) has an incidence rate ranging from 0.3% to 3% and is a result of an embryological misadventure. Typically, the primitive cardinal veins come together and, along with the regression of the left supracardinal vein, leave a solitary, right-sided vena cava. Here we review the relevant anatomy and clinical significance of a D-IVC and present a case of successful laparoscopic donor nephrectomy in a patient with this anomaly. C1 [Saidi, Reza F.; Markmann, James F.; Ko, Dicken S. C.; Kawai, Tatsuo; Yeh, Heidi] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kennealey, Peter T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kennealey, PT (reprint author), Porter Adventis Hosp, Centura Hlth Transplant Program, Denver, CO USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0090-2934 J9 DIALYSIS TRANSPLANT JI Dial. Transplant. PD OCT PY 2009 VL 38 IS 10 BP 420 EP + PG 2 WC Engineering, Biomedical; Transplantation; Urology & Nephrology SC Engineering; Transplantation; Urology & Nephrology GA 512EL UT WOS:000271226800015 ER PT J AU Mizumori, M Akiba, Y Kaunitz, JD AF Mizumori, Misa Akiba, Yasutada Kaunitz, Jonathan D. TI Lubiprostone Stimulates Duodenal Bicarbonate Secretion in Rats SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE ClC-2; EP receptor; Water secretion; CFTR; Prostaglandin ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CHLORIDE CHANNEL ACTIVATOR; IRRITABLE-BOWEL-SYNDROME; SMALL-INTESTINE; CLINICAL-TRIAL; CLC-2; CELLS; CONSTIPATION; BARRIER; MUCOSA AB Lubiprostone, a bicyclic fatty acid, is used for the treatment of chronic constipation. No published study has addressed the effect of lubiprostone on intestinal ion secretion in vivo. The aim of this study was to test the hypothesis that lubiprostone augments duodenal HCO(3) (-) secretion (DBS). Rat proximal duodenal loops were perfused with pH 7.0 Krebs, control vehicle (medium-chain triglycerides), or lubiprostone (0.1-10 mu M). We measured DBS with flow-through pH and CO(2) electrodes, perfusate [Cl(-)] with a Cl(-) electrode, and water flux using a non-absorbable ferrocyanide marker. Some rats were pretreated with a potent, selective CFTR antagonist, CFTR(inh)-172 (1 mg/kg, ip), 1 h before experiments. Perfusion of lubiprostone concentration dependently increased DBS, whereas net Cl(-) output and net water output were only increased at 0.1 mu M, compared with vehicle. CFTR(inh)-172 reduced lubiprostone (10 mu M)-induced DBS increase, whereas net Cl(-) output was also unchanged. Nevertheless, CFTR(inh)-172 reduced basal net water output, which was reversed by lubiprostone. Furthermore, lubiprostone-induced DBS was inhibited by EP4 receptor antagonist, not by an EP1/2 receptor antagonist or by indomethacin pretreatment. In this first study of the effect of lubiprostone on intestinal ion secretion in vivo, lubiprostone stimulated CFTR-dependent DBS without changing net Cl(-) secretion. This effect supports the hypothesis that Cl(-) secreted by CFTR is recycled across the apical membrane by anion exchangers. Recovery of water output during CFTR inhibition suggests that lubiprostone may improve the intestinal phenotype in CF patients. Furthermore, increased DBS suggests that lubiprostone may protect the duodenum from acid-induced injury via EP4 receptor activation. C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] W Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. [Mizumori, Misa; Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Akiba, Yasutada; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles VA Med Ctr, 11301 Wilshire Blvd,Bldg 114,Suite 217, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Takeda North America [07-014L]; Department of Veterans Affairs Merit Review Award; NIH-NIDDK [R01 DK54221, P30 DK0413] FX We thank Jenifer Kugler for her assistance with manuscript preparation. This work was supported by a research grant from Takeda North America No. 07-014L, Department of Veterans Affairs Merit Review Award, NIH-NIDDK R01 DK54221 (J. Kaunitz), and the animal core of NIH-NIDDK P30 DK0413 (J.E. Rozengurt). NR 27 TC 17 Z9 17 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2009 VL 54 IS 10 BP 2063 EP 2069 DI 10.1007/s10620-009-0907-0 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 490UK UT WOS:000269531900003 PM 19657734 ER PT J AU Hur, C Broughton, DE Kong, CY Ozanne, EM Richards, EB Truong, T Gazelle, GS AF Hur, Chin Broughton, Darcy E. Kong, Chung Yin Ozanne, Elissa M. Richards, Ethan B. Truong, Thanh Gazelle, G. Scott TI Patient Preferences for the Chemoprevention of Colorectal Cancer SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Colorectal cancer; Chemoprevention; Aspirin; Celecoxib; Patient preferences ID COST-EFFECTIVENESS ANALYSIS; CORONARY-HEART-DISEASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIALS; PRIMARY PREVENTION; CARDIOVASCULAR EVENTS; RHEUMATOID-ARTHRITIS; LIFETIME RISK; ASPIRIN; CELECOXIB AB Although evidence suggests that aspirin and celecoxib may reduce the risk of colorectal cancer (CRC), these drugs can also cause harmful side effects. The aim of this study was to characterize patient preferences for celecoxib and aspirin. Participants completed a computer-based patient decision-making questionnaire that included an educational component outlining the benefits and harms of celecoxib and aspirin. Under the base conditions 7.4% would take celecoxib and 43.6% would take aspirin; males were more willing than females to take aspirin. Patients identified the increased risk of myocardial infarction and gastrointestinal events as the primary reasons for their unwillingness to take celecoxib and aspirin, respectively. A majority of subjects would not take either drug, after considering their benefits and harms, although participants were almost six times more likely to take aspirin than celecoxib. These data serve to inform physicians and researchers regarding the variability and factors that affect patient preferences for CRC chemoprevention. C1 [Hur, Chin; Kong, Chung Yin; Ozanne, Elissa M.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Hur, Chin; Broughton, Darcy E.; Richards, Ethan B.; Truong, Thanh] Massachusetts Gen Hosp Unit, Gastrointestinal Unit, Boston, MA USA. [Hur, Chin; Kong, Chung Yin; Ozanne, Elissa M.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU NCI NIH HHS [K07 CA107060, K07CA107060] NR 25 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2009 VL 54 IS 10 BP 2207 EP 2214 DI 10.1007/s10620-008-0609-z PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 490UK UT WOS:000269531900022 PM 19057995 ER PT J AU Verdine, GL AF Verdine, Gregory L. TI DRUGGING THE "UNDRUGGABLE" SO DRUGS OF THE FUTURE LA English DT Meeting Abstract C1 [Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Chem Biol Initiat & Program Canc Chem Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD OCT PY 2009 VL 34 SU A BP 46 EP 47 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 561NG UT WOS:000274983700024 ER PT J AU Johnson, B AF Johnson, B. TI Targeted therapies directed against EML4-ALK translocations and BRAF mutations in patients with lung cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC/NCI/ASCO on Molecular Markers in Cancer CY OCT 15-17, 2009 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Johnson, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2009 VL 7 IS 4 BP 4 EP 4 PG 1 WC Oncology SC Oncology GA 536CC UT WOS:000273018800017 ER PT J AU Oh, W Magidson, J Bankaitis-Davis, D Siconolfi, L Schurko, B Cantu, R Braitsch, S Wassman, K Kantoff, P Ross, R AF Oh, W. Magidson, J. Bankaitis-Davis, D. Siconolfi, L. Schurko, B. Cantu, R. Braitsch, S. Wassman, K. Kantoff, P. Ross, R. TI A whole blood RNA transcript-based model to predict biopsy Gleason score in newly diagnosed prostate cancer patients SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC/NCI/ASCO on Molecular Markers in Cancer CY OCT 15-17, 2009 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Oh, W.] Mt Sinai Sch Med, New York, NY 10029 USA. [Schurko, B.; Kantoff, P.; Ross, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2009 VL 7 IS 4 BP 27 EP 27 PG 1 WC Oncology SC Oncology GA 536CC UT WOS:000273018800096 ER PT J AU Tsai, CL Camargo, CA AF Tsai, C-L Camargo, C. A., Jr. TI The role of body mass index in acute exacerbations of chronic obstructive pulmonary disease SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID COPD; MULTICENTER; BMI AB Background: Low body mass index (BMI) is a strong prognostic marker in stable chronic obstructive pulmonary disease (COPD); however, little is known about its role in acute exacerbations of COPD. Objectives: To determine the prevalence and determinants of low BMI in emergency department (ED) patients with acute exacerbations of COPD, and to examine whether low BMI was associated with more severe acute exacerbations, more intensive ED treatments and worse post-ED outcomes. Methods: A secondary analysis was performed using data from a prospective multicentre cohort study involving 29 ED in the USA and Canada. Using a standard protocol, ED patients with acute exacerbations of COPD were interviewed and their charts reviewed. BMI was calculated using self-reported weight and height. Main outcome measures included hospital admission, post-ED relapse and ongoing exacerbation. Results: 395 patients were enrolled. Their median age was 69 years (interquartile range 62-76); 52% were women. Thirteen per cent (95% CI 10% to 16%) were underweight, 37% normal weight, 27% overweight and 23% were obese. Current smoking was independently associated with underweight (OR 5.4, 95% CI 1.1 to 25.2). In the propensity-matched cohort, there were no significant differences in severity of exacerbation, treatments received in the ED, or short-term clinical outcomes, according to BMI. Conclusions: Low BMI is not uncommon in patients with acute exacerbations of COPD, and current smoking is associated with low BMI in these patients. Unlike its role in stable COPD, BMI appears to have little impact on exacerbation severity, treatments received in the ED, and short-term clinical outcomes in acute exacerbations of COPD. C1 [Tsai, C-L] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr,Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr,Sch Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Boehringer Ingelheim (Ridgefield, CT); AstraZeneca (Wilmington, DE); Dey (Napa, CA); GlaxoSmithKline (Research Triangle Park, NC); Merck (Rahway, NJ); Novartis (East Hanover, NJ); Respironics (Cedar Grove, NJ); Schering Plough (Kenilworth, NJ) FX Competing interests: Declared. CAC has received financial support (eg, research grants, consulting and lecture honoraria) from AstraZeneca (Wilmington, DE), Dey (Napa, CA), GlaxoSmithKline (Research Triangle Park, NC), Merck (Rahway, NJ), Novartis (East Hanover, NJ), Respironics (Cedar Grove, NJ) and Schering Plough (Kenilworth, NJ). C-LT declares no conflicts of interest. NR 20 TC 3 Z9 3 U1 1 U2 3 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 OCT PY 2009 VL 26 IS 10 BP 701 EP 705 DI 10.1136/emj.2008.068478 PG 5 WC Emergency Medicine SC Emergency Medicine GA 497GJ UT WOS:000270045600007 PM 19773486 ER PT J AU Barrett, LF Bliss-Moreau, E AF Barrett, Lisa Feldman Bliss-Moreau, Eliza TI She's Emotional. He's Having a Bad Day: Attributional Explanations for Emotion Stereotypes SO EMOTION LA English DT Article DE emotion; attribution; sex differences ID SPONTANEOUS TRAIT INFERENCES; SEX-ROLE STEREOTYPES; FACIAL EXPRESSIONS; SOCIAL-ROLE; GENDER; EXPERIENCE; PERCEPTION; SMILE; METAANALYSIS; APPEARANCE AB People believe that women are the more emotional sex. This belief stems less from what men and women actually do than from the explanations given for their behaviors. In 2 studies, participants who were given situational information about the causes of emotional expression in target faces nonetheless more frequently judged feminine targets depicting emotions as "emotional" (i.e., a dispositional attribution for the emotional behavior), whereas they more frequently judged masculine targets as "having a bad day" (i.e., a situational attribution for the emotional behavior). These findings help explain the pervasive belief that women are more emotional when compared with men, even when the scientific veracity of this belief is questionable. C1 [Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Cambridge, MA 02138 USA. [Bliss-Moreau, Eliza] Univ Calif Davis, Dept Psychiat & Behav Sci, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. RP Barrett, LF (reprint author), Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. EM barretli@bc.edu FU NIH HHS [DP1OD003312]; NIMH NIH HHS [K02 MH001981] NR 63 TC 33 Z9 35 U1 0 U2 23 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD OCT PY 2009 VL 9 IS 5 BP 649 EP 658 DI 10.1037/a0016821 PG 10 WC Psychology, Experimental SC Psychology GA 505NH UT WOS:000270700100006 PM 19803587 ER PT J AU Gendron, M Barrett, LF AF Gendron, Maria Barrett, Lisa Feldman TI Reconstructing the Past: A Century of Ideas About Emotion in Psychology SO EMOTION REVIEW LA English DT Article DE affect; appraisal; basic emotion; emotion; history; psychological construction AB Within the discipline of psychology, the conventional history outlines the development of two fundamental approaches to the scientific study of emotion-"basic emotion" and "appraisal" traditions. In this article, we outline the development of a third approach to emotion that exists in the psychological literature-the "psychological constructionist" tradition. In the process, we discuss a number of works that have virtually disappeared from the citation trail in psychological discussions of emotion. We also correct some misconceptions about early sources, such as work by Darwin and James. Taken together, these three contributions make for a fuller and more accurate account of ideas about emotion during the century stretching from 1855 to just before 1960. C1 [Gendron, Maria; Barrett, Lisa Feldman] Boston Coll, Chestnut Hill, MA 02467 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Gendron, M (reprint author), Boston Coll, 301 McGuinn Hall, Chestnut Hill, MA 02467 USA. EM gendroma@bc.edu FU NIA NIH HHS [R01 AG030311, R01 AG030311-04]; NIH HHS [DP1 OD003312, DP1 OD003312-03] NR 174 TC 55 Z9 55 U1 4 U2 26 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1754-0739 J9 EMOT REV JI Emot. Rev. PD OCT PY 2009 VL 1 IS 4 SI SI BP 316 EP 339 DI 10.1177/1754073909338877 PG 24 WC Psychology, Multidisciplinary SC Psychology GA V24CB UT WOS:000208387400004 PM 20221412 ER PT J AU Wasterlain, CG Suchomelova, L Matagne, A Klitgaard, H Niquet, J Baldwin, R AF Wasterlain, C. G. Suchomelova, L. Matagne, A. Klitgaard, H. Niquet, J. Baldwin, R. TI SHORT-TERM AND LONG-TERM EFFECTS OF BRIVARACETAM IN AN ANIMAL MODEL OF STATUS SO EPILEPSIA LA English DT Meeting Abstract CT 28th International Epilespy Congress CY 2009 CL Budapest, HUNGARY C1 [Wasterlain, C. G.; Suchomelova, L.; Niquet, J.; Baldwin, R.] VA Greater Angeles Hlth Care Syst, Epilepsy Res Lab, Los Angeles, CA USA. [Wasterlain, C. G.; Suchomelova, L.; Niquet, J.; Baldwin, R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 OCT PY 2009 VL 50 BP 13 EP 13 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 502DB UT WOS:000270433800043 ER PT J AU Nguyen, V Tran, H Makhijani, V Nguyen, C Shah, N Kaunitz, J Dergalust, S AF Nguyen, V. Tran, H. Makhijani, V. Nguyen, C. Shah, N. Kaunitz, J. Dergalust, S. TI ANTIEPILEPTIC DRUG MONOTHERAPY IN A VETERAL POPULATION SO EPILEPSIA LA English DT Meeting Abstract CT 28th International Epilespy Congress CY 2009 CL Budapest, HUNGARY C1 [Nguyen, V.; Tran, H.; Makhijani, V.; Nguyen, C.; Shah, N.; Kaunitz, J.; Dergalust, S.] Vet Affairs Greater Los Angeles, Los Angeles, CA USA. [Nguyen, V.] Univ So Calif, Los Angeles, CA 90089 USA. [Tran, H.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2009 VL 50 BP 110 EP 111 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 502DB UT WOS:000270433800401 ER PT J AU Parko, K Thurman, DJ AF Parko, Karen Thurman, David J. TI Prevalence of epilepsy and seizures in the Navajo Nation 1998-2002 SO EPILEPSIA LA English DT Article DE Epidemiology; Health disparities; Native American; Global health AB P>Purpose: To determine the prevalence of epilepsy and seizures in the Navajo. Methods: We studied 226,496 Navajo residing in the Navajo Reservation who had at least one medical encounter between October 1, 1998 and September 30, 2002. We ascertained and confirmed cases in two phases. First, we identified patients with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes signifying epilepsy or seizures using Indian Health Service (IHS) administrative data. Second, we reviewed medical charts of a geographic subpopulation of identified patients to confirm diagnoses and assess the positive predictive value of the ICD-9-CM codes in identifying patients with active epilepsy. Results: Two percent of Navajo receiving IHS care were found to have an ICD-9-CM code consistent with epilepsy or seizures. Based on confirmed cases, the crude prevalence for the occurrence of any seizure (including febrile seizures and recurrent seizures that may have been provoked) in the geographic subpopulation was 13.5 per 1,000 and the crude prevalence of active epilepsy was 9.2 per 1,000. Prevalence was higher among males, children under 5 years of age, and older adults. Discussion: The estimated prevalence of active epilepsy in the Navajo Nation is above the upper limit of the range of reported estimates from other comparable studies of U.S. communities. C1 [Parko, Karen] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Parko, Karen] San Francisco VA Med Ctr, San Francisco, CA USA. [Thurman, David J.] Ctr Dis Control & Prevent, Div Adult & Community Hlth, Epilepsy Program, Atlanta, GA USA. RP Parko, K (reprint author), 4150 Clement St 127, San Francisco, CA 94121 USA. EM Karen.Parko@ucsf.edu OI Thurman, David/0000-0002-0533-7062 FU CDC National Center for Chronic Disease Prevention and Health Promotion; Indian Health Service Information Technology; Shiprock Service Unit Health Board; Richard Champany DDS; CEO; Northern Navajo Medical Center; National IHS IRB; Navajo Nation Human Research Review Board FX The authors thank the following for their direct assistance: Indian Health Service Information Technology Support Center; Anne Butman, management analyst, DataCom Sciences; Yolinda Cadman; Dr. Nathanial Cobb; Navajo Area medical records department; Northern Navajo Medical Center in Shiprock: Gary Russell-King, in Kayenta: Lorraine Dohi, in Crownpoint: Cynthia Begaye; Clinical pharmacists in the NNMC seizure clinic: Tom Duran, Lauren Dolence, Melissa Stahlecker, Dr. David Labiner, Karla Lindquist, Peter Taylor, and Elena Cherkasova. This work could not have been undertaken without the support from: Duane H. Yazzie and the Shiprock Chapter House; Manuel Morgan and the Shiprock Service Unit Health Board; Richard Champany DDS, CEO, Northern Navajo Medical Center; Phillip Smith, MD, MPH and the National IHS IRB; and Beverly Pigman and the Navajo Nation Human Research Review Board. NR 0 TC 19 Z9 19 U1 0 U2 3 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 OCT PY 2009 VL 50 IS 10 BP 2180 EP 2185 DI 10.1111/j.1528-1167.2009.02140.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 498GW UT WOS:000270126300002 PM 19490040 ER PT J AU Leeman, BA Leveroni, CL Johnson, KA AF Leeman, Beth A. Leveroni, Catherine L. Johnson, Keith A. TI Does hippocampal FDG-PET asymmetry predict verbal memory dysfunction after left temporal lobectomy? SO EPILEPSY & BEHAVIOR LA English DT Article DE Positron emission tomography; Fluorodeoxyglucose; Seizure; Epilepsy; Temporal lobectomy; Verbal memory; Hippocampus; Asymmetry ID LOBE EPILEPSY; GLUCOSE-METABOLISM; HYPOMETABOLISM; MRI; SURGERY; WADA AB The primary aim of this study was to determine whether hippocampal asymmetries in fluorodeoxyglucose (FDG) uptake on preoperative PET scans would predict post-temporal lobectomy verbal memory (VM) decline in patients with left temporal lobe epilepsy. A quantitative asymmetry index (AI) of uptake values within a hippocampal region of interest (ROI) was defined by an automated technique. No statistically significant effect of the hippocampal AI on the outcome measure, the pre- to postsurgical change in Logical Memory Percent Retention, was evident. Post hoc analyses revealed that AIs of the superior and inferior temporal gyri approached significance, however, with relatively greater left-sided preoperative metabolism predicting better VM outcomes. This finding suggests reorganization of function and/or retained function of remaining tissue. Although hippocampal FDG-PET asymmetries did not significantly predict changes in VM, the predictive value of neocortical AIs should be further explored. Automated ROI parcellation provides a feasible tool for use in such investigations. (C) 2009 Elsevier Inc. All rights reserved. C1 [Leeman, Beth A.] Beth Israel Deaconess Med Ctr, Behav Neurol Unit, Dept Neurol, Boston, MA 02215 USA. [Leeman, Beth A.; Leveroni, Catherine L.; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Leeman, Beth A.; Leveroni, Catherine L.; Johnson, Keith A.] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Leeman, BA (reprint author), Beth Israel Deaconess Med Ctr, Behav Neurol Unit, Dept Neurol, 330 Brookline Ave,KS 2, Boston, MA 02215 USA. EM bleeman1@bidmc.harvard.edu FU Harvard Medical School Scholars in Clinical Science Program [K30 RR022292-07] FX This work was supported by the Harvard Medical School Scholars in Clinical Science Program (K30 RR022292-07). The authors thank Dr. Steven Schachter, Dr. Blaise Bourgeois, Dr. Daniel Hoch, and Dr. Steven Greenberg for their invaluable comments regarding the protocol and data analysis. NR 25 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2009 VL 16 IS 2 BP 274 EP 280 DI 10.1016/j.yebeh.2009.07.035 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 510JG UT WOS:000271083800013 PM 19726233 ER PT J AU Aleong, RG Singh, SM Levinson, JR Milan, DJ AF Aleong, Ryan G. Singh, Sheldon M. Levinson, John R. Milan, David J. TI Catecholamine challenge unmasking high-risk features in the Wolff-Parkinson-White syndrome SO EUROPACE LA English DT Article AB Risk stratification in patients with Wolff-Parkinson-White (WPW) syndrome is an important clinical problem given a small, but significant risk of sudden death. It has been widely accepted that intermittent pre-excitation is associated with a low-risk pathway. We report a case of WPW with intermittent pre-excitation at baseline, but with marked sensitivity to adrenergic stimulation, revealed by exercise and isoproterenol administration. C1 [Aleong, Ryan G.; Singh, Sheldon M.; Levinson, John R.; Milan, David J.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Milan, DJ (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM dmilan@partners.org NR 5 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD OCT PY 2009 VL 11 IS 10 BP 1396 EP 1398 DI 10.1093/europace/eup211 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 499KC UT WOS:000270218000030 PM 19654129 ER PT J AU Alberts, MJ Bhatt, DL Mas, JL Ohman, EM Hirsch, AT Rother, J Salette, G Goto, S Smith, SC Liau, CS Wilson, PWF Steg, PG AF Alberts, Mark J. Bhatt, Deepak L. Mas, Jean-Louis Ohman, E. Magnus Hirsch, Alan T. Roether, Joachim Salette, Genevieve Goto, Shinya Smith, Sidney C., Jr. Liau, Chiau-Suong Wilson, Peter W. F. Steg, Ph. Gabriel CA REduction Atherothrombosis Continu TI Three-year follow-up and event rates in the international REduction of Atherothrombosis for Continued Health Registry SO EUROPEAN HEART JOURNAL LA English DT Article DE Atherothrombosis; Risk factors; Coronary artery disease; Cerebrovascular disease; Peripheral arterial disease ID ACUTE MYOCARDIAL-INFARCTION; GLOBAL BURDEN; RISK-FACTORS; CARDIOVASCULAR-DISEASES; LIFE-STYLE; STROKE; COSTS; PREVENTION; GENDER; ATTACK AB Aims To determine 3-year event rates in outpatients with vascular disease enrolled in the REduction of Atherothrombosis for Continued Health (REACH) Registry. Methods and results REACH enrolled 67 888 outpatients with atherothrombosis [established coronary artery disease (CAD), cerebrovascutar disease, or peripheral arterial disease (PAD)], or with at least three atherothrombotic risk factors, from 44 countries. Among the 55 499 patients at baseline with symptomatic disease, 39 675 were eligible for 3-year follow-up, and 32 247 had data available (81% retention rate). Among the symptomatic patients at 3 years, 92% were taking an antithrombotic agent, 91% an anti hypertensive, and 76% were on Upid-lowering therapy. For myocardial infarction (Ml)/stroke/vascutar death, 1 - and 3-year event rates for all patients were 4.2 and 11.0%, respectively. Event rates (MI/stroke/vascutar death) were significantly higher for patients with symptomatic disease vs. those with risk factors only at 1 year (4.7 vs. 2.3%, P < 0.001) and at 3 years (12.0 vs. 6.0%, P < 0.001). One and 3-year rates of MI/stroke/vascular cleath/rehospitatization were 14.4 and 28.4%, respectively, for patients with symptomatic disease. Rehospitalization for a vascular event other than Mi/stroke/vascular death was common at 3 years (19.0% overall; 33.6% for PAD; 23.0% for CAD). For patients with symptomatic vascular disease in one vascular bed vs. multiple vascular beds, 3-year event rates for MI/stroke/vascular death/rehospitalization were 25.5 vs. 40.5% (P < 0.001). Conclusion Despite contemporary therapy, outpatients with symptomatic atherothrombotic vascular disease experience high rates of recurrent vascular events and rehospitalizations. C1 [Alberts, Mark J.] Northwestern Univ, Dept Neurol, Sch Med, Chicago, IL 60611 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mas, Jean-Louis] Paris Descartes Univ, Hop St Anne, Dept Neurol, INSERM U894, Paris, France. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Roether, Joachim] Johannes Wesling Klinikum, Acad Teaching Hosp, Hannover Med Sch, Dept Neurol, Minden, Germany. [Salette, Genevieve] Sanofi Aventis, Paris, France. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC 27515 USA. [Liau, Chiau-Suong] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Wilson, Peter W. F.] Atlanta VA Med Ctr, Atlanta, GA USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Atlanta, GA USA. [Steg, Ph. Gabriel] Univ Paris 07, AP HP, INSERM, U698, Paris, France. RP Bhatt, DL (reprint author), Northwestern Univ, Dept Neurol, Sch Med, 710 N Lake Shore Dr,Room 1420, Chicago, IL 60611 USA. EM m-alberts@northwestern.edu NR 23 TC 103 Z9 105 U1 5 U2 12 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 OCT PY 2009 VL 30 IS 19 BP 2318 EP 2326 DI 10.1093/eurheartj/ehp355 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 503BG UT WOS:000270505900015 PM 19720633 ER PT J AU Park, KP Yim, YB Foerch, C Lo, EH AF Park, K. -P. Yim, Y. -B. Foerch, C. Lo, E. H. TI Plasma MMP-9 as a biomarker of acute cerebral ischemia SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 13th Congress of the European-Federation-of-Neurological-Societies CY SEP 12-15, 2009 CL Florence, ITALY SP European Federat Neurol Soc C1 [Park, K. -P.] Pusan Natl Univ, Dept Neurol, Yangsan Hosp, Yangsan, South Korea. [Park, K. -P.] Pusan Natl Univ, Sch Med, Yangsan, South Korea. [Park, K. -P.; Foerch, C.; Lo, E. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA USA. [Yim, Y. -B.] Bong Seng Mem Hosp, Dept Neurol, Pusan, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD OCT PY 2009 VL 16 BP 125 EP 125 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 494IC UT WOS:000269804100274 ER PT J AU Vandenbark, A AF Vandenbark, A. TI Results of a phase I safety study of RTL1000, a recombinant T-Cell receptor ligand specific for an immunodominant MOG peptide, in multiple sclerosis SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 13th Congress of the European-Federation-of-Neurological-Societies CY SEP 12-15, 2009 CL Florence, ITALY SP European Federat Neurol Soc C1 [Vandenbark, A.] Portland VA Med Ctr, Portland, OR USA. [Vandenbark, A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD OCT PY 2009 VL 16 BP 249 EP 249 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 494IC UT WOS:000269804100523 ER PT J AU Offner, H AF Offner, H. TI Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in EAE by a single recombinant TCR ligand (RTL) SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 13th Congress of the European-Federation-of-Neurological-Societies CY SEP 12-15, 2009 CL Florence, ITALY SP European Federat Neurol Soc C1 [Offner, H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Offner, H.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD OCT PY 2009 VL 16 BP 570 EP 570 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 494IC UT WOS:000269804101162 ER PT J AU Chakera, AH Hesse, B Burak, Z Ballinger, JR Britten, A Caraco, C Cochran, AJ Cook, MG Drzewiecki, KT Essner, R Even-Sapir, E Eggermont, AMM Stopar, TG Ingvar, C Mihm, MC McCarthy, SW Mozzillo, N Nieweg, OE Scolyer, RA Starz, H Thompson, JF Trifiro, G Viale, G Vidal-Sicart, S Uren, R Waddington, W Chiti, A Spatz, A Testori, A AF Chakera, Annette H. Hesse, Birger Burak, Zeynep Ballinger, James R. Britten, Allan Caraco, Corrado Cochran, Alistair J. Cook, Martin G. Drzewiecki, Krzysztof T. Essner, Richard Even-Sapir, Einat Eggermont, Alexander M. M. Stopar, Tanja Gmeiner Ingvar, Christian Mihm, Martin C., Jr. McCarthy, Stanley W. Mozzillo, Nicola Nieweg, Omgo E. Scolyer, Richard A. Starz, Hans Thompson, John F. Trifiro, Giuseppe Viale, Giuseppe Vidal-Sicart, Sergi Uren, Roger Waddington, Wendy Chiti, Arturo Spatz, Alain Testori, Alessandro TI EANM-EORTC general recommendations for sentinel node diagnostics in melanoma SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Review DE Blue dye; Gamma probe; Lymphoscintigraphy; Melanoma; Pathology; Sentinel node ID EARLY-STAGE MELANOMA; INTRAOPERATIVE GAMMA-PROBE; RADIATION SAFETY CONSIDERATIONS; MALIGNANT CUTANEOUS MELANOMA; NEEDLE-ASPIRATION-CYTOLOGY; AMERICAN JOINT COMMITTEE; WIDE LOCAL EXCISION; LYMPH-NODE; BREAST-CANCER; FOLLOW-UP AB The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, ( 8) use of dye, ( 9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination. C1 [Chakera, Annette H.] Univ Copenhagen Hosp, Dept Plast Surg, Sect 2102, Rigshosp, DK-2100 Copenhagen, Denmark. [Chakera, Annette H.] Univ Copenhagen Hosp, Burns Unit, Sect 2102, Rigshosp, DK-2100 Copenhagen, Denmark. [Hesse, Birger] Rigshosp, Dept Nucl Med, DK-2100 Copenhagen, Denmark. [Hesse, Birger] Rigshosp, PET, DK-2100 Copenhagen, Denmark. [Burak, Zeynep] Ege Univ, Fac Med, Dept Nucl Med, Izmir, Turkey. [Ballinger, James R.] Guys & St Thomas NHS Fdn Trust, Dept Nucl Med, London, England. [Britten, Allan] St Georges Healthcare NHS Trust, Med Phys & Bioengn, London, England. [Caraco, Corrado; Mozzillo, Nicola] Natl Canc Inst, Naples, Italy. [Cochran, Alistair J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Cook, Martin G.] Royal Surrey Cty Hosp, Guildford, Surrey, England. [Cook, Martin G.] Univ Surrey, Guildford GU2 5XH, Surrey, England. [Essner, Richard] Univ Calif Los Angeles, Sch Med, Calif Oncol Res Inst, Santa Monica, CA USA. [Even-Sapir, Einat] Tel Aviv Univ, Sackler Sch Med, Dept Nucl Med, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Eggermont, Alexander M. M.] Erasmus Univ MC, Daniel den Hoed Canc Ctr, NL-3075 EA Rotterdam, Netherlands. [Stopar, Tanja Gmeiner] Univ Med Ctr Ljubljana, Dept Nucl Med, Ljubljana, Slovenia. [Ingvar, Christian] Univ Lund Hosp, Dept Surg, S-22185 Lund, Sweden. [Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCarthy, Stanley W.; Scolyer, Richard A.] Royal Prince Alfred Hosp, Dept Anat Pathol, Sydney, NSW, Australia. [Nieweg, Omgo E.] Netherlands Canc Inst, Dept Surg, Amsterdam, Netherlands. [Thompson, John F.] Royal Prince Alfred Hosp, Sydney Melanoma Unit, Melanoma Inst Australia, Sydney, NSW, Australia. [Scolyer, Richard A.] Univ Sydney, Discipline Pathol, Sydney, NSW 2006, Australia. [Starz, Hans] Klinikum Augsburg Sued, Dept Dermatol & Allergol, Augsburg, Germany. [Thompson, John F.] Mater Hosp, Sydney Melanoma Unit, Melanoma Inst Australia, Sydney, NSW, Australia. [Thompson, John F.] Univ Sydney, Discipline Surg, Sydney, NSW 2006, Australia. [Trifiro, Giuseppe] European Inst Oncol, Div Nucl Med, Milan, Italy. [Viale, Giuseppe] Univ Milan, Sch Med, European Inst Oncol, Milan, Italy. [Vidal-Sicart, Sergi] Hosp Clin Barcelona, Dept Nucl Med, Barcelona, Spain. [Uren, Roger] Univ Sydney, Discipline Med, RPAH Med Ctr, Sydney, NSW 2006, Australia. [Waddington, Wendy] UCL Hosp NHS Fdn Trust, UCL Inst Nucl Med, London, England. [Chiti, Arturo] Ist Clin Humanitas, Rozzano, MI, Italy. [Spatz, Alain] Inst Gustave Roussy, Dept Pathol, Villejuif, France. [Testori, Alessandro] European Inst Oncol, Div Melanoma & Muscle Cutaneous Sarcomas, Milan, Italy. RP Chakera, AH (reprint author), Univ Copenhagen Hosp, Dept Plast Surg, Sect 2102, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM annette.hougaard.chakera@live.dk RI Chiti, Arturo/K-6524-2016; OI Chiti, Arturo/0000-0002-5806-1856; Scolyer, Richard/0000-0002-8991-0013 NR 172 TC 78 Z9 79 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2009 VL 36 IS 10 BP 1713 EP 1742 DI 10.1007/s00259-009-1228-4 PG 30 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 502HS UT WOS:000270449000023 PM 19714329 ER PT J AU Boland, GWL Guimaraes, AS Mueller, PR AF Boland, Giles W. L. Guimaraes, Alexander S. Mueller, Peter R. TI The evolving radiology landscape: the importance of effective leadership SO EUROPEAN RADIOLOGY LA English DT Editorial Material DE Leadership; Radiologist; Outsourcing; Turf; Teleradiology ID CHANGING RELATIONSHIPS; HOSPITALS; ISSUES AB Advances in technology and imaging techniques have propelled radiology into the centre of diagnostic and therapeutic medicine. However, all this Success has come at a price, with radiology departments persistently struggling to keep up with increasing demand. In response, radiologists in many countries are giving up an increasing proportion of their traditional workload, often driven by teleradiology, causing them to become less visible within their organizations. As such, radiologists now risk being viewed as commodities by their peers. The failure to meet the increasing stakeholder expectations is, at least in part, due to lack of radiology leadership. While the drivers for the radiology profession and the organizational structures for radiologists vary from country to country, this article will discuss the characteristics of good leadership and how these can be used to ensure radiologists remain centre stage in the provision of high-quality clinical care in any healthcare environment. C1 [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 21 TC 5 Z9 5 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD OCT PY 2009 VL 19 IS 10 BP 2321 EP 2325 DI 10.1007/s00330-009-1427-1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 500AG UT WOS:000270268700001 PM 19471944 ER PT J AU Wang, Y Zhang, YG Zhang, XS Wang, Z Mao, KY Chen, C Zheng, GQ Li, G Wood, KB AF Wang, Yan Zhang, YongGang Zhang, XueSong Wang, Zheng Mao, Keya Chen, Cao Zheng, GuoQuan Li, Gang Wood, Kirkham B. TI Posterior-only multilevel modified vertebral column resection for extremely severe Pott's kyphotic deformity SO EUROPEAN SPINE JOURNAL LA English DT Article DE Pott's kyphosis; Multilevel; Vertebral column resection; Osteotomy ID PEDICLE SUBTRACTION OSTEOTOMY; SPINAL TUBERCULOSIS; KYPHOSIS; SPONDYLITIS; ANTERIOR; DISEASE AB Extremely severe Pott's kyphotic deformity cannot be completely corrected by conventional techniques, including vertebral body resection, Smith-Peterson, pedicle subtraction osteotomy or even vertebral column resection (VCR). The authors developed a new technique combining transpedicular eggshell osteotomies and VCR as multilevel modified vertebral column resection (MVCR) through a single posterior approach for surgical treatment of Pott's kyphosis with Konstam's angle beyond 90 degrees. A total of 9 patients (6 males, 3 females) in our institution with severe Pott's kyphosis who underwent single-stage posterior-only multilevel MVCR were retrospectively reviewed. The candidates for multilevel MVCR were those with a sharp, angular kyphosis in the lower thoracic or upper lumbar spine with a Konstam's angle beyond 90 degrees. The follow-up averaged 30.6 months (ranging from 21 to 50 months). Fusion status was evaluated at each follow-up by CT three-dimensional reconstruction images. An average of 2.5 vertebrae was removed in each case (ranging from 2 to 4 vertebrae). A mean of 7 vertebrae were fused (ranging from 6 to 11 vertebrae). The mean duration of surgery was 285 min (ranging from 246 to 400 min), the average intraoperative blood loss was 2,933 ml (ranging from 2,000 to 6,000 ml). The mean preoperative kyphus was 100.3 degrees (ranging from 90 degrees to 132 degrees). The mean kyphosis in the immediate postoperative period was 15.9 degrees (ranging from 4 degrees to 30 degrees) with an average postoperative kyphos correction of 84.4 degrees (ranging from 63 degrees to 126 degrees). Fusion of the resection site was confirmed on radiographs in all patients at the minimum 12 months follow-up. No pseudo-arthrosis was found. No loosening or breakage of pedicle screws occurred. A single-stage posterior-only multilevel MVCR is an effective way to correct extremely severe Pott's kyphosis with Konstam's angle beyond 90 degrees. C1 [Wang, Yan; Zhang, YongGang; Zhang, XueSong; Wang, Zheng; Mao, Keya; Chen, Cao; Zheng, GuoQuan] Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed, Beijing 100853, Peoples R China. [Li, Gang; Wood, Kirkham B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Wang, Y (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed, Beijing 100853, Peoples R China. EM 301wangyan@sina.com NR 21 TC 20 Z9 26 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD OCT PY 2009 VL 18 IS 10 BP 1436 EP 1441 DI 10.1007/s00586-009-1067-9 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 500EN UT WOS:000270281300004 PM 19526375 ER PT J AU Bellmunt, J Rosenberg, JE Choueiri, TK AF Bellmunt, Joaquim Rosenberg, Jonathan E. Choueiri, Toni K. TI Recent Progress and Pitfalls in Testing Novel Agents in Castration-Resistant Prostate Cancer SO EUROPEAN UROLOGY LA English DT Editorial Material ID PHASE-II; DOCETAXEL; THERAPY; SM-153; TRIAL C1 [Bellmunt, Joaquim] Pompeu Fabra Univ, Univ Hosp Mar IMIM, Barcelona 08003, Spain. [Bellmunt, Joaquim; Rosenberg, Jonathan E.; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellmunt, Joaquim; Rosenberg, Jonathan E.; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. RP Bellmunt, J (reprint author), Pompeu Fabra Univ, Univ Hosp Mar IMIM, Passeig Maritim 25-29, Barcelona 08003, Spain. EM j.bellmunt@imas.imim.es NR 15 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD OCT PY 2009 VL 56 IS 4 BP 606 EP 608 DI 10.1016/j.eururo.2009.07.015 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 497PG UT WOS:000270071700005 PM 19635642 ER PT J AU Seetharaman, SV Prudencio, M Karch, C Holloway, SP Borchelt, DR Hart, PJ AF Seetharaman, Sai V. Prudencio, Mercedes Karch, Celeste Holloway, Stephen P. Borchelt, David R. Hart, P. John TI Immature Copper-Zinc Superoxide Dismutase and Familial Amyotrophic Lateral Sclerosis SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE superoxide dismutase; SOD1; amyotrophic lateral sclerosis; motor neuron disease; protein misfolding; protein aggregation; protofibrils; amyloid ID MOTOR-NEURON DISEASE; SOD1 GENE MUTATION; INTRACYTOPLASMIC HYALINE INCLUSIONS; POSTERIOR COLUMN INVOLVEMENT; MISSENSE POINT MUTATION; BASE-PAIR DELETION; CU,ZN-SUPEROXIDE DISMUTASE; TRANSGENIC MICE; MUTANT SOD1; WILD-TYPE AB Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease, motor neuron disease). Insoluble forms of mutant SOD1 accumulate in neural tissues of human ALS patients and in spinal cords of transgenic mice expressing these polypeptides, suggesting that SOD1-linked ALS is a protein misfolding disorder. Understanding the molecular basis for how the pathogenic mutations give rise to SOD1 folding intermediates, which may themselves be toxic, is therefore of keen interest. A critical step on the SOD1 folding pathway occurs when the copper chaperone for SOD1 (CCS) modifies the nascent SOD1 polypeptide by inserting the catalytic copper cofactor and oxidizing its intrasubunit disulfide bond. Recent studies reveal that pathogenic SOD1 proteins coming from cultured cells and from the spinal cords of transgenic mice tend to be metal-deficient and/or lacking the disulfide bond, raising the possibility that the disease-causing mutations may enhance levels of SOD1-folding intermediates by preventing or hindering CCS-mediated SOD1 maturation. This mini-review explores this hypothesis by highlighting the structural and biophysical properties of the pathogenic SOD1 mutants in the context of what is currently known about CCS structure and action. Other hypotheses as to the nature of toxicity inherent in pathogenic SOD1 proteins are not covered. Exp Biol Med 234:1140-1154, 2009 C1 [Seetharaman, Sai V.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Seetharaman, Sai V.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Prudencio, Mercedes; Karch, Celeste; Borchelt, David R.] Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA. [Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Hart, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM pjhart@biochem.uthscsa.edu OI Karch, Celeste/0000-0002-6854-5547; Prudencio, Mercedes/0000-0002-4894-4858 FU NIH/NINDS; ALS Association; Welch Foundation; Packard Foundation; William and Ella C. Owens Medical Research Foundation; Judith and Jean Pape Adams Charitable Foundation FX This work has been supported over the years by the NIH/NINDS (PJH/DRB), the ALS Association (P.J.H./D.R.B.). the Robert A. Welch Foundation (P.J.H.), the Packard Foundation (D.R.B.), the William and Ella C. Owens Medical Research Foundation (P.J.H.), and the Judith and Jean Pape Adams Charitable Foundation (P.J.H.). Support for the X-ray Crystallography Core Laboratory by the Executive Research Council at the University of Texas Health Science Center is gratefully acknowledged. NR 138 TC 45 Z9 47 U1 1 U2 5 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2009 VL 234 IS 10 BP 1140 EP 1154 DI 10.3181/0903-MR-104 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 501AC UT WOS:000270347800004 PM 19596823 ER PT J AU Dietrich, J Wang, D Batchelor, TT AF Dietrich, Joerg Wang, Daphne Batchelor, Tracy T. TI Cediranib: profile of a novel anti-angiogenic agent in patients with glioblastoma SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Editorial Material DE adverse effects; angiogenesis; AZD2171; brain tumors; cediranib; cerebral edema; glioblastoma; invasion; malignant glioma; stem cells ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; BEVACIZUMAB PLUS IRINOTECAN; HYPOXIA-INDUCIBLE FACTOR-1; FACTOR SIGNALING INHIBITOR; TUMOR ANGIOGENESIS; FACTOR RECEPTOR; CLINICAL-TRIALS; PHASE-II; IN-VIVO AB Background: Treatment strategies targeting angiogenesis have revealed promising results in preclinical studies and early clinical trials in patients with glioblastomas. Objective: This review evaluates the preclinical and clinical data for cediranib (AZD2171), a potent oral inhibitor of the VEGF receptor tyrosine kinase. Methods: We summarize both preclinical and clinical data for cediranib, with a focus on the treatment of glioblastomas. Results/conclusion: Cediranib is an effective drug in patients with glioblastoma, acting through inhibition of angiogenesis and normalization of tumor vasculature. Reduction of vasogenic brain edema is a key component of its treatment effect in this patient population. The primary side effects of cediranib include fatigue, diarrhea and hypertension. C1 [Dietrich, Joerg; Wang, Daphne; 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 [R21 CA117079-02, R01 CA129371, R01CA129371, K24 CA125440, R21CA117079, K24 CA125440-02, R21 CA117079, R01 CA129371-02]; PHS HHS [KCA125440A] NR 56 TC 29 Z9 29 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD OCT PY 2009 VL 18 IS 10 BP 1549 EP 1557 DI 10.1517/13543780903183528 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 506KB UT WOS:000270772600012 PM 19671039 ER PT J AU Hayes, TG AF Hayes, Teresa G. TI Pharmacologic treatment of male breast cancer SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE aromatase; chemotherapy; hormonal therapy; male breast cancer; orchiectomy; tamoxifen ID FIRST-LINE THERAPY; ADJUVANT CHEMOTHERAPY; AROMATASE INHIBITOR; PROGNOSTIC-FACTORS; HORMONAL-THERAPY; BRCA2 MUTATIONS; POSTMENOPAUSAL WOMEN; COMPLETE REMISSION; POSTOPERATIVE RADIOTHERAPY; KLINEFELTERS-SYNDROME AB Male breast cancer is an uncommon condition. It often occurs in settings in which there is an imbalance between androgens and oestrogens. Genetics plays an important role, as many cases are associated with mutations in BRCA2 or other genes. Male breast cancer occurs at an older age than female breast cancer and is frequently diagnosed at a later stage. Tumors are predominantly oestrogen and progesterone positive. Prognosis is approximately equivalent to that of breast cancer in females when matched for age, stage and hormonal receptors. The recommended treatment for male breast cancer is similar to that for breast cancer in postmenopausal females. However, the presence of androgens in males has a strong effect on the hormonal milieu and the ability of male patients to respond to hormonal agents. When pharmacologic treatment is required, tamoxifen is effective for first-line therapy. Other hormonal approaches such as orchiectomy, aromatase inhibitors and androgen ablation may be useful in later lines of therapy. C1 Baylor Coll Med, Hematol Oncol Sect, Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Hayes, TG (reprint author), Baylor Coll Med, Hematol Oncol Sect, Dept Vet Affairs Med Ctr, VA 111H,2002 Holcombe Blvd, Houston, TX 77030 USA. EM thayes@bcm.edu FU Michael E DeBakey Veterans Administration Medical Center FX This material is the result of work supported with resources and the use of facilities at the Michael E DeBakey Veterans Administration Medical Center. NR 201 TC 6 Z9 8 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD OCT PY 2009 VL 10 IS 15 BP 2499 EP 2510 DI 10.1517/14656560903200634 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509IQ UT WOS:000271009200009 PM 19708850 ER PT J AU Stedman, J Roccaro, A Ghobrial, IM AF Stedman, Jennifer Roccaro, Aldo Ghobrial, Irene M. TI Individualizing treatment for Waldenstrom's macroglobulinemia SO EXPERT REVIEW OF HEMATOLOGY LA English DT Editorial Material ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; EXTENDED RITUXIMAB THERAPY; COOPERATIVE-ONCOLOGY-GROUP; WAIDENSTROMS MACROGLOBULINEMIA; PROGNOSTIC-FACTORS; FLUDARABINE THERAPY; PLUS RITUXIMAB; PHASE-II; BORTEZOMIB C1 [Stedman, Jennifer; Roccaro, Aldo; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Roccaro, Aldo/0000-0002-1872-5128 NR 45 TC 1 Z9 1 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD OCT PY 2009 VL 2 IS 5 BP 473 EP 476 DI 10.1586/EHM.09.51 PG 4 WC Hematology SC Hematology GA 687TQ UT WOS:000284801200001 PM 21083011 ER PT J AU Matros, E Momoh, A Yaremchuk, MJ AF Matros, E. Momoh, A. Yaremchuk, M. J. TI The Aging Midfacial Skeleton: Implications for Rejuvenation and Reconstruction Using Implants SO FACIAL PLASTIC SURGERY LA English DT Article DE Implants; aging; midface; skeleton ID DEEP-PLANE RHYTIDECTOMY; AESTHETIC SURGERY; BLEPHAROPLASTY; AGE; AUGMENTATION; MORPHOLOGY AB Traditional theories on facial aging and methods for rejuvenation focus primarily on soft tissues with ptosis as the major mechanism responsible for senescent changes. Anatomic studies demonstrate that there are also many changes to the craniofacial skeleton as patients age. Midface skeletal augmentation, using implants made of porous polyethylene, is a simple and effective method to reverse age-related changes of the facial skeleton in patients with intact occlusion. Skeletal implants correct concave morphology by increasing projection and provide a means to resuspend cheek soft tissues that have descended off a deficient bony platform. Beyond rejuvenation, skeletal implants can be used to restore facial proportions in patients with midface deficiency secondary to trauma, congenital deformity, or other pathologic states. C1 [Matros, E.; Momoh, A.; Yaremchuk, M. J.] Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, Boston, MA 02114 USA. [Matros, E.; Momoh, A.; Yaremchuk, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Momoh, A.] Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, Wang 435,15 Parkman St, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 40 TC 13 Z9 13 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD OCT PY 2009 VL 25 IS 4 BP 252 EP 259 DI 10.1055/s-0029-1242037 PG 8 WC Surgery SC Surgery GA 527RC UT WOS:000272383200006 PM 19924598 ER PT J AU Vandenburgh, H Shansky, J Benesch-Lee, F Skelly, K Spinazzola, JM Saponjian, Y Tseng, BS AF Vandenburgh, Herman Shansky, Janet Benesch-Lee, Frank Skelly, Kirsten Spinazzola, Janelle M. Saponjian, Yero Tseng, Brian S. TI Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts SO FASEB JOURNAL LA English DT Article DE tetanic force; glucocorticoids; mdx mouse; dietary supplements; cardiovascular drugs ID DUCHENNE MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; MDX MICE; THERAPEUTIC STRATEGIES; GLYCOPROTEIN COMPLEX; MOUSE; STRENGTH; PREDNISOLONE; STRETCH; PROTEIN AB Identification of factors that improve muscle function in boys with Duchenne muscular dystrophy (DMD) could lead to an improved quality of life. To establish a functional in vitro assay for muscle strength, mdx murine myoblasts, the genetic homologue of DMD, were tissue engineered in 96-microwell plates into 3-dimensional muscle constructs with parallel arrays of striated muscle fibers. When electrically stimulated, they generated tetanic forces measured with an automated motion tracking system. Thirty-one compounds of interest as potential treatments for patients with DMD were tested at 3 to 6 concentrations. Eleven of the compounds (insulin-like growth factor-1, creatine, beta-hydroxy-beta-methylbutyrate, trichostatin A, lisinopril, and 6 from the glucocorticoid family) significantly increased tetanic force relative to placebo-treated controls. The glucocorticoids methylprednisolone, deflazacort, and prednisone increased tetanic forces at low doses (EC(50) of 6, 19, and 56 nM, respectively), indicating a direct muscle mechanism by which they may be benefitting DMD patients. The tetanic force assay also identified beneficial compound interactions ( arginine plus deflazacort and prednisone plus creatine) as well as deleterious interactions ( prednisone plus creatine inhibited by pentoxifylline) of combinatorial therapies taken by some DMD patients. Since mdx muscle in vivo and DMD patients respond in a similar manner to many of these compounds, the in vitro assay will be a useful tool for the rapid identification of new potential treatments for muscle weakness in DMD and other muscle disorders.-Vandenburgh, H., Shansky, J., Benesch-Lee, F., Skelly, K., Spinazzola, J. M., Saponjian, Y., Tseng, B. S. Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts. FASEB J. 23, 3325-3334 ( 2009). www.fasebj.org C1 [Vandenburgh, Herman] Myomics Inc, Slater Biotechnol Ctr, Providence, RI 02906 USA. [Vandenburgh, Herman; Shansky, Janet] Miriam Hosp, Brown Med Sch, Dept Pathol, Providence, RI 02906 USA. [Saponjian, Yero; Tseng, Brian S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vandenburgh, H (reprint author), Myomics Inc, Slater Biotechnol Ctr, 5th Floor,4 Richmond Sq, Providence, RI 02906 USA. EM hvandenburgh@myomics.com RI Benesch-Lee, Frank/O-2482-2014 OI Benesch-Lee, Frank/0000-0002-4551-3163 FU Slater Technology Fund; National Institutes of Health [AG-029705, NS-059098, AR-052308]; National Science Foundation [0724445]; Hood, Sharp, and Jett Foundations; Charley's Fund FX We thank Dr. Terry Partridge ( Children's National Medical Center, Washington, DC, USA) for providing the conditionally immortalized control and mdx skeletal muscle cells. This work was supported by the Slater Technology Fund; the National Institutes of Health (AG-029705, NS-059098, and AR-052308); the National Science Foundation ( award 0724445); the Hood, Sharp, and Jett Foundations; and Charley's Fund. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and not necessarily those of the granting agencies. H. V. and B. T. designed the experiments and wrote the paper; J.S., K. S., and J.M.S. performed the tissue engineering, compound screening, and force measurements; F.B.-L. developed the casting molds for the micropost plugs, wrote the LabView and MatLab software, and built the MAD device; and Y.S. performed histological analyses. NR 55 TC 35 Z9 35 U1 4 U2 14 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 OCT PY 2009 VL 23 IS 10 BP 3325 EP 3334 DI 10.1096/fj.09-134411 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 501BQ UT WOS:000270354300010 PM 19487307 ER PT J AU Zhang, XF Kazerounian, S Duquette, M Perruzzi, C Nagy, JA Dvorak, HF Parangi, S Lawler, J AF Zhang, Xuefeng Kazerounian, Shideh Duquette, Mark Perruzzi, Carole Nagy, Janice A. Dvorak, Harold F. Parangi, Sareh Lawler, Jack TI Thrombospondin-1 modulates vascular endothelial growth factor activity at the receptor level SO FASEB JOURNAL LA English DT Article DE KDR; angiogenesis; integrin; CD36; VEGFR2 ID NITRIC-OXIDE; TUMOR-GROWTH; TYPE-1 REPEATS; DEFICIENT MICE; ANGIOGENESIS; CELLS; INHIBITION; PROTEINS; VEGF; BINDING AB Vascular endothelial growth factor ( VEGF) is a well-established stimulator of vascular permeability and angiogenesis, whereas thrombospondin-1 (TSP-1) is a potent angiogenic inhibitor. In this study, we have found that the TSP-1 receptors CD36 and beta 1 integrin associate with the VEGF receptor 2 (VEGFR2). The coclustering of receptors that regulate angiogenesis may provide the endothelial cell with a platform for integration of positive and negative signals in the plane of the membrane. Thus, this complex may represent a molecular switch that regulates angiogenesis and determines endothelial cell behavior. In this context, physiological levels of TSP-1 appear to support VEGFR2 function on both the cellular and tissue level, because phosphorylation of VEGFR2 and vascular permeability in response to VEGF are decreased in TSP-1-null mice and isolated endothelial cells. A therapeutic agent based on the antiangiogenic domain of TSP-1, designated 3TSR ( for three TSP-1 type 1 repeats), has significant antiangiogenic and antitumor efficacy. Systemic treatment of wild-type mice with 3TSR significantly decreased VEGF-induced permeability. Consistent with this result, VEGF-stimulated phosphorylation of VEGFR2 was also significantly decreased in lung extracts from 3TSR-treated mice. Moreover, 3TSR significantly decreased VEGF-stimulated VEGFR2 phosphorylation in human dermal microvascular endothelial cells in culture. Taken together, the results indicate that TSP-1 and 3TSR modulate the function of VEGFR2.-Zhang, X., Kazerounian, S., Duquette, M., Perruzzi, C., Nagy, J. A., Dvorak, H. J., Parangi, S., and Lawler, J. Thrombospondin-1 modulates vascular endothelial growth factor activity at the receptor level. FASEB J. 23, 3368-3376 ( 2009). www.fasebj.org C1 [Zhang, Xuefeng; Kazerounian, Shideh; Duquette, Mark; Perruzzi, Carole; Nagy, Janice A.; Dvorak, Harold F.; Lawler, Jack] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Boston, MA 02215 USA. [Zhang, Xuefeng; Kazerounian, Shideh; Duquette, Mark; Perruzzi, Carole; Nagy, Janice A.; Dvorak, Harold F.; Parangi, Sareh; Lawler, Jack] Harvard Univ, Sch Med, Boston, MA USA. [Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lawler, J (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, 330 Brookline Ave,EC-CLS-503, Boston, MA 02215 USA. EM jlawler@bidmc.harvard.edu FU NIH [CA92644, CA130895] FX We thank Dr. Richard O. Hynes ( Massachusetts Institute of Technology, Cambridge, MA, USA) for antibodies of beta 1 integrin and Sami Lawler and Raji Bhat for help in preparing the manuscript. This work was supported by NIH grants CA92644 and CA130895. NR 48 TC 52 Z9 53 U1 0 U2 6 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 OCT PY 2009 VL 23 IS 10 BP 3368 EP 3376 DI 10.1096/fj.09-131649 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 501BQ UT WOS:000270354300014 PM 19528255 ER PT J AU Salmon, AB Perez, VI Bokov, A Jernigan, A Kim, G Zhao, H Levine, RL Richardson, A AF Salmon, Adam B. Perez, Viviana I. Bokov, Alex Jernigan, Amanda Kim, Geumsoo Zhao, Hang Levine, Rodney L. Richardson, Arlan TI Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span SO FASEB JOURNAL LA English DT Article DE longevity; free radical; stress resistance; aging; antioxidant ID FIBROBLAST CELL-LINES; ANTIOXIDANT ENZYMES; MULTIPLE FORMS; KNOCKOUT MOUSE; DWARF MICE; RESISTANCE; MSRA; DAMAGE; GENE; OVEREXPRESSION AB Methionine sulfoxide reductase A (MsrA) repairs oxidized methionine residues within proteins and may also function as a general antioxidant. Previous reports have suggested that modulation of MsrA in mice and mammalian cell culture can affect the accumulation of oxidized proteins and may regulate resistance to oxidative stress. Thus, under the oxidative stress theory of aging, these results would predict that MsrA regulates the aging process in mammals. We show here that MsrA(-/-) mice are more susceptible to oxidative stress induced by paraquat. Skin-derived fibroblasts do not express MsrA, but fibroblasts cultured from MsrA(-/-) mice were, nevertheless, also more susceptible to killing by various oxidative stresses. In contrast to previous reports, we find no evidence for neuromuscular dysfunction in MsrA(-/-) mice in either young adult or in older animals. Most important, we found no difference between MsrA(-/-) and control mice in either their median or maximum life span. Thus, our results show that MsrA regulates sensitivity to oxidative stress in mice but has no effect on aging, as determined by life span.-Salmon, A. B., Perez, V. I., Bokov, A., Jernigan, A., Kim, G., Zhao, H., Levine, R. L., Richardson, A. Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span. FASEB J. 23, 3601-3608 (2009). www.fasebj.org C1 [Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Kim, Geumsoo; Zhao, Hang; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Richardson, Arlan] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM richardsona@uthscsa.edu RI Zhao, Hang/A-2558-2012; Levine, Rodney/D-9885-2011 FU National Institutes of Health (NIH) [T32 AG021890-05, R37AG026557]; San Antonio Nathan Shock Center for Excellence in the Basic Biology of Aging; National Heart, Lung, and Blood Institute FX We thank Jay Cox, Marian Sabia, and Quy Fung for assistance in animal care. We also thank Dr. James Harper for statistical analysis assistance and intellectual discourse. This study was supported by National Institutes of Health (NIH) training grant T32 AG021890-05 (A. B. S.), NIH MERIT grant R37AG026557 (A. R.), the San Antonio Nathan Shock Center for Excellence in the Basic Biology of Aging (A.R.), and the Intramural Research Program of the National Heart, Lung, and Blood Institute (G.K., H.Z., and R.L.L.). NR 44 TC 63 Z9 65 U1 0 U2 4 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 OCT PY 2009 VL 23 IS 10 BP 3601 EP 3608 DI 10.1096/fj.08-127415 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 501BQ UT WOS:000270354300036 PM 19487311 ER PT J AU Sandborn, WJ Rutgeerts, P Feagan, BG Reinisch, W Olson, A Johanns, J Lu, JD Horgan, K Rachmilewitz, D Hanauer, SB Lichtenstein, GR de Villiers, WJS Present, D Sands, BE Colombel, JF AF Sandborn, William J. Rutgeerts, Paul Feagan, Brian G. Reinisch, Walter Olson, Allan Johanns, Jewel Lu, Jiandong Horgan, Kevin Rachmilewitz, Daniel Hanauer, Stephen B. Lichtenstein, Gary R. de Villiers, Willem J. S. Present, Daniel Sands, Bruce E. Colombel, Jean Frederic TI Colectomy Rate Comparison After Treatment of Ulcerative Colitis With Placebo or Infliximab SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; POUCH-ANAL ANASTOMOSIS; HOSPITALIZATION RATES; UNITED-STATES; THERAPY; COHORT; RISK; CANCER; MAINTENANCE; ANTIBODY AB BACKGROUND & AIMS: The efficacy of infliximab for treating patients with ulcerative colitis has been established. METHODS: The Active Ulcerative Colitis Trial (ACT)-1 and ACT-2 randomized, double-blind, placebo-controlled studies evaluated infliximab Induction and maintenance therapy in moderately to severely active ulcerative colitis. Overall, 728 patients received placebo or infliximab (S or 10 mg/kg) intravenously at weeks 0, 2, and 6, then every 8 weeks through week 46 (ACT-1) or 22 (ACT-2). Colectomy hospitalization, and surgery/procedure data through 54 weeks after the first infusion were obtained from ACT-1 ACT-2, and associated data sources. In the prespecified analysis, all data were combined to ascertain time to colectomy. Kaplan-Meier product-limit method was used to estimate the cumulative incidence of colectomy, and log-rank test was used to compare the combined infliximab group and placebo. RESULTS: Eighty-seven percent (630 of 728) of patients had complete colectomy follow-up; 13% (98 of 728) of patients had a median follow-up of 6.2 months. The cumulative incidence of colectomy through 54 weeks was 10% for infliximab and 17% for placebo (P = .02), yielding an absolute risk reduction of 7%. Compared with placebo, fewer ulcerative colitis-related hospitalizations and surgeries/procedures per 100 patient-years of treatment occurred with infliximab therapy: 40 vs 20 (P = .003) and 34 vs 21(P =.03), respectively. Serious adverse events occurring in infliximab-treated patients included serious infections, tuberculosis, histoplasmosis, listeriosis, and malignancy. CONCLUSIONS: Patients with moderately to severely active ulcerative colitis treated with infliximab were less likely to undergo colectomy through 54 weeks than those receiving placebo. C1 [Sandborn, William J.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. [Rutgeerts, Paul] Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium. [Feagan, Brian G.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada. [Reinisch, Walter] AKH Wien, Univ Klin Innere Med 4, Dept Gastroenterol Hepatol, Vienna, Austria. [Olson, Allan] RW Johnson Pharmaceut Res & Dev, San Diego, CA USA. [Johanns, Jewel; Lu, Jiandong; Horgan, Kevin] Centocor Res & Dev Inc, Malvern, PA USA. [Rachmilewitz, Daniel] Shaare Zedek Med Ctr, Div Med, Jerusalem, Israel. [Hanauer, Stephen B.] Univ Chicago, Div Gastroenterol, Chicago, IL 60637 USA. [Lichtenstein, Gary R.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [de Villiers, Willem J. S.] Univ Kentucky, Dept Med, Div Digest Dis & Nutr, Lexington, KY 40506 USA. [Present, Daniel] Mt Sinai Med Ctr, Div Gastroenterol, Dept Med, New York, NY 10029 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Colombel, Jean Frederic] CHU Lille, Dept Hepatogastroenterol, Hop Claude Huriez, F-59037 Lille, France. [Colombel, Jean Frederic] CHU Lille, Ctr Invest Clin, F-59037 Lille, France. RP Sandborn, WJ (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. EM sandborn.william@mayo.edu RI Feagan, Brian/M-4283-2015; OI Horgan, Kevin/0000-0003-0647-9078 FU Centocor Research and Development, Inc, Malvern, Pennsylvania; Schering Plough, Kenilworth, New Jersey; National Center for Research Resources [1-UL1-RR024150-01]; National Institutes of Health (NIH; NIH Roadmap for Medical Research FX Supported by a research grant from Centocor Research and Development, Inc, Malvern, Pennsylvania, and Schering Plough, Kenilworth, New Jersey. Supported by a grant (1-UL1-RR024150-01) from the National Center for Research Resources, a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research. NR 29 TC 244 Z9 250 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2009 VL 137 IS 4 BP 1250 EP 1260 DI 10.1053/j.gastro.2009.06.061 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 499VT UT WOS:000270255200018 PM 19596014 ER PT J AU Matharu, KS Mizoguchi, E Cotoner, CA Nguyen, DD Mingle, B Iweala, OI Mcbee, ME Stefka, AT Prioult, G Haigis, KM Bhan, AK Snapper, SB Murakami, H Schauer, DB Reinecker, HC Mizoguchi, A Nagler, CR AF Matharu, Kabir S. Mizoguchi, Emiko Cotoner, Carmen Alonso Nguyen, Deanna D. Mingle, Bethany Iweala, Onyinye I. Mcbee, Megan E. Stefka, Andrew T. Prioult, Guenolee Haigis, Kevin M. Bhan, Atul K. Snapper, Scott B. Murakami, Hidehiro Schauer, David B. Reinecker, Hans-Christian Mizoguchi, Atsushi Nagler, Cathryn R. TI Toll-Like Receptor 4-Mediated Regulation of Spontaneous Helicobacter-Dependent Colitis in IL-10-Deficient Mice SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; T-CELL; AUTOIMMUNE-DISEASE; APOPTOTIC CELLS; INTERLEUKIN-10; HEPATICUS; INNATE; FOXP3(+); REVEAL; IL-17 AB BACKGROUND & AIMS: The commensal microbiota is believed to have an important role in regulating immune responsiveness and preventing intestinal inflammation. Intestinal microbes produce signals that regulate inflammation via Toll-like receptor (TLR) signaling, but the mechanisms of this process are poorly understood. We investigated the role of the anti-inflammatory cytokine interleukin (IL)-10 in this signaling pathway using a mouse model of colitis. METHODS: Clinical, histopathologic, and functional parameters of intestinal inflammation were evaluated in TLR4(-/-), IL-10(-/-), and TLR4(-/-) X IL-10(-/-) mice that were free of specific pathogens and in TLR4(-/-) X IL-10(-/-) mice following eradication and reintroduction of Helicobacter hepaticus. Regulatory T-cell (Treg) function was evaluated by crossing each of the lines with transgenic mice that express green fluorescent protein under control of the endogenous regulatory elements of Foxp3. Apoptotic cells in the colonic lamina propria were detected by a TUNEL assay. RESULTS: TLR4-mediated signals have 2 interrelated roles in promoting inflammation in TLR4(-/-) X IL-10(-/-) mice. In the absence of TLR4-mediated signals, secretion of proinflammatory and immunoregulatory cytokines is dysregulated. Tregs (Foxp3(+)) that secrete interferon-gamma and IL-17 accumulate in the colonic lamina propria of TLR4(-/-) X IL-10(-/-) mice and do not prevent inflammation. Aberrant control of epithelial cell turnover results in the persistence of antigen-presenting cells that contain apoptotic epithelial fragments in the colonic lamina propria of Helicobacter-infected TLR4(-/-) mice. CONCLUSIONS: In mice that lack both IL-10- and TLR4-mediated signals, aberrant regulatory T-cell function and dysregulated control of epithelial homeostasis combine to exacerbate intestinal inflammation. C1 [Mingle, Bethany; Iweala, Onyinye I.; Stefka, Andrew T.; Prioult, Guenolee; Murakami, Hidehiro; Nagler, Cathryn R.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Matharu, Kabir S.; Mizoguchi, Emiko; Cotoner, Carmen Alonso; Nguyen, Deanna D.; Mingle, Bethany; Iweala, Onyinye I.; Stefka, Andrew T.; Haigis, Kevin M.; Bhan, Atul K.; Snapper, Scott B.; Reinecker, Hans-Christian; Mizoguchi, Atsushi; Nagler, Cathryn R.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Mizoguchi, Emiko; Cotoner, Carmen Alonso; Nguyen, Deanna D.; Snapper, Scott B.; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mcbee, Megan E.; Schauer, David B.; Mizoguchi, Atsushi] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Prioult, Guenolee] Nestle Res Ctr, CH-1000 Lausanne, Switzerland. [Haigis, Kevin M.; Murakami, Hidehiro] Ehime Univ, Sch Med, Matsuyama, Ehime 790, Japan. [Matharu, Kabir S.] Massachusetts Gen Hosp, Mol Pathol Canc Ctr, Boston, MA 02114 USA. [Bhan, Atul K.] Massachusetts Gen Hosp, Expt Pathol Unit, Boston, MA 02114 USA. RP Nagler, CR (reprint author), Univ Chicago, Dept Pathol, BSD, 5841 S Maryland Ave,MC 3083, Chicago, IL 60637 USA. EM cnagler@bsd.uchicago.edu RI Alonso-Cotoner, Carmen/N-7057-2014 OI Alonso-Cotoner, Carmen/0000-0002-3483-2919 FU Massachusetts General Hospital CSIBD; NIH [DK 55678, DK 06818, DK 64351, DK 64289, DK 74454, DK 052413]; Eli and Edythe L. Broad Medical foundation; AGA Jon Isenberg International Scholar Award [T32 EY07156, F31AI054229, T32DKO07191] FX Supported by the Massachusetts General Hospital CSIBD and NIH grants DK 55678 (to C.R.N.); DK 06818 (to H.C.R.); DK 64351 (to A.M.); DK 64289; DK 74454 (to E.M.); DK 052413 (to D.S.); the Eli and Edythe L. Broad Medical foundation (to E.M., A.M.); training fellowships T32 EY07156 (to B.M.), F31AI054229 (to 0.1.1.), and T32DKO07191 (to D.N.); and by the AGA Jon Isenberg International Scholar Award (to C.A.C.). NR 35 TC 34 Z9 36 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 OCT PY 2009 VL 137 IS 4 BP 1380 EP 1390 DI 10.1053/j.gastro.2009.07.004 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 499VT UT WOS:000270255200030 PM 19596011 ER PT J AU Zhou, W Cao, Q Peng, Y Zhang, QJ Castrillon, DH Depinho, RA Liu, ZP AF Zhou, Wen Cao, Qian Peng, Yan Zhang, Qing-Jun Castrillon, Diego H. Depinho, Ronald A. Liu, Zhi-Ping TI FoxO4 Inhibits NF-kappa 3 and Protects Mice Against Colonic Injury and Inflammation SO GASTROENTEROLOGY LA English DT Article ID NF-KAPPA-B; BOWEL-DISEASE; INTESTINAL INFLAMMATION; ALPHA; ACTIVATION; EXPRESSION; COLITIS; MODELS; CELLS; HOMEOSTASIS AB BACKGROUND & AIMS: FoxO4 is a member of the forkhead box transcription factor O (FoxO) subfamily. FoxO, proteins are involved in diverse biological processes. In this study, we examine the role of FoxO4 in intestinal mucosal immunity and inflammatory bowel disease (IBD). METHODS: Foxo4-null mice were subjected to trinitrobenzene sulfonic acid (TNBS) treatment. Microarray analysis and quantitative reverse transcription polymerase chain reaction were used to identify the cytokine transcripts that were altered by Foxo4 deletion. The effects of Foxo4 deficiency on the intestinal epithelial permeability and levels of tight junction proteins were examined by permeable fluorescent dye and Western blot. The molecular and cellular mechanisms by which FoxO4 regulates the mucosal immunity were explored through immunologic and biochemical analyses. The expression level of FoxO4 in intestinal epithelial cells of patients with IBD was examined with immunohistochemistry. RESULTS: Foxo4-null mice were more susceptible to TNBS injury-induced colitis. The chemokine CCL5 is significantly up-regulated in the colonic epithelial cells of Foxo4-null mice, with increased recruitment of CD4(+) intraepithelial T cells and up-regulation of cytokines interferon-gamma and tumor necrosis factor-a in the colon. Foxo4 deficiency also resulted in an increase in intestinal epithelial permeability and down-regulation of the tight junction proteins ZO-1 and claudin-1. Mechanistically, FoxO4 inhibited the transcriptional activity of nuclear factor-kappa B (NF-kappa B), and Foxo4 defciency is associated with increased NF-kappa B activity in vivo. FoxO4 transcription is transiently repressed in response to TNBS treatment and in patients with IBD. CONCLUSION: These results indicate that FoxO4 is an endogenous inhibitor of NF-kappa B and identify a novel function of FoxO4 in the regulation of NF-kappa B-mediated mucosal immunity. C1 [Zhou, Wen; Zhang, Qing-Jun; Liu, Zhi-Ping] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Zhou, Wen; Zhang, Qing-Jun; Liu, Zhi-Ping] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Cao, Qian] Zhejiang Univ, Sch Med, Dept Gastroenterol, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China. [Peng, Yan; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Depinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci,Dept Med Oncol, Boston, MA 02115 USA. [Depinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci,Ctr Appl Canc Sc, Boston, MA 02115 USA. [Depinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Depinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Liu, ZP (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, 6000 Harry Hines Blvd, Dallas, TX 75390 USA. EM zhi-ping.liu@utsouthwestern.edu FU American Heart Association; Texas Advanced Research Program [010019-0070-2007]; National Heart, Lung, and Blood Institute [R01 HL085749]; Zhejiang Provincial Natural Science Foundation of China [R2080029]; Ellison Medical Foundation; Renee E. and Robert A. Belfer Institute for Innovative Cancer Science FX This study was supported by the American Heart Association (scientist development grant to Z.-P.L.), the Texas Advanced Research Program (grant 010019-0070-2007 to Z.-P.L.), the National Heart, Lung, and Blood Institute (R01 HL085749 to Z.-P.L.), and Zhejiang Provincial Natural Science Foundation of China (no. R2080029 to Q.C.). R.A.D. is an American Society Research Professor and Senior Scholar of the Ellison Medical Foundation and is supported by the Renee E. and Robert A. Belfer Institute for Innovative Cancer Science. NR 30 TC 52 Z9 60 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2009 VL 137 IS 4 BP 1403 EP 1414 DI 10.1053/j.gastro.2009.06.049 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 499VT UT WOS:000270255200032 PM 19560465 ER PT J AU Corradini, E Garuti, C Montosi, G Ventura, P Andriopoulos, B Lin, HY Pietrangelo, A Babitt, JL AF Corradini, Elena Garuti, Cinzia Montosi, Giuliana Ventura, Paolo Andriopoulos, Billy, Jr. Lin, Herbert Y. Pietrangelo, Antonello Babitt, Jodie L. TI Bone Morphogenetic Protein Signaling Is Impaired in an Hfe Knockout Mouse Model of Hemochromatosis SO GASTROENTEROLOGY LA English DT Article ID REGULATES HEPCIDIN EXPRESSION; CELL-SURFACE EXPRESSION; TRANSFERRIN RECEPTOR; HEREDITARY HEMOCHROMATOSIS; IRON OVERLOAD; JUVENILE HEMOCHROMATOSIS; LIVER; GENE; BINDING; HEMOJUVELIN AB BACKGROUND AND AIMS: Mutations in HFE are the most common cause of the iron-overload disorder hereditary hemochromatosis. Levels of the main iron regulatory hormone, hepcidin, are inappropriately low in hereditary hemochromatosis mouse models and patients with HFE mutations, indicating that HFE regulates hepcidin. The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is an important endogenous regulator of hepcidin expression. We investigated whether HFE is involved in BMP6 -SMAD regulation of hepcidin expression. METHODS: The BMP6-SMAD pathway was examined in Hfe knockout (KO) mice and in wild-type (WT) mice as controls. Mice were placed on diets of varying iron content. Hepcidin induction by BMP6 was examined in primary hepatocytes from Hfe KO mice; data were compared with those of WT mice. RESULTS: Liver levels of Bmp6 messenger RNA (mRNA) were higher in Hfe KO mice; these were appropriate for the increased hepatic levels of iron in these mice, compared with WT mice. However, levels of hepatic phosphorylated Smad 1/5/8 protein (an intracellular mediator of Bmp6 signaling) and Id1 mRNA (a target gene of Bmp6) were inappropriately low for the body iron burden and Bmp6 mRNA levels in Hfe KO, compared with WT mice. BMP6 induction of hepcidin expression was reduced in Hfe KO hepatocytes compared with WT hepatocytes. CONCLUSIONS: HFE is not involved in regulation of BMP6 by iron, but does regulate the downstream signals of BMP6 that are triggered by iron. C1 [Corradini, Elena; Andriopoulos, Billy, Jr.; Lin, Herbert Y.; Babitt, Jodie L.] Harvard Univ, Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol,Div Nephrol,Med Sch, Boston, MA 02114 USA. [Corradini, Elena; Garuti, Cinzia; Montosi, Giuliana; Ventura, Paolo; Pietrangelo, Antonello] Univ Hosp Modena & Reggio Emilia, Ctr Hemochromatosis, Modena, Italy. RP Babitt, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol,Div Nephrol,Med Sch, 185 Cambridge St,CPZN 8216, Boston, MA 02114 USA. EM babitt.jodie@mgh.harvard.edu RI Corradini, Elena/O-4167-2016; Pietrangelo, Antonello/K-1517-2016 OI Corradini, Elena/0000-0001-9477-2164; Pietrangelo, Antonello/0000-0002-7411-935X FU European Union [EUROIRON Ct. 2006-037296]; Italian Ministry of University and Research; National Institutes of Health [ROI DK-069533, ROI DK-071837, K08 DK-075846]; Massachusetts General Hospital FX Antonello Pletrangelo and Elena Corradinl were supported In part by the European Union (EUROIRON Ct. 2006-037296) and the Italian Ministry of University and Research (MIUR-2006) grants; Herbert Y. Lin was supported In part by National Institutes of Health grants ROI DK-069533 and ROI DK-071837; and Jodie L. Babitt was supported in part by National Institutes of Health grant K08 DK-075846 and by a Claflin Distinguished Scholar Award from the Massachusetts General Hospital. NR 49 TC 83 Z9 86 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 OCT PY 2009 VL 137 IS 4 BP 1489 EP 1497 DI 10.1053/j.gastro.2009.06.057 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 499VT UT WOS:000270255200040 PM 19591830 ER PT J AU DeWitt, J McGreevy, K Schmidt, CM Brugge, WR AF DeWitt, John McGreevy, Kathleen Schmidt, Christian M. Brugge, William R. TI EUS-guided ethanol versus saline solution lavage for pancreatic cysts: a randomized, double-blind study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID SIMPLE RENAL CYSTS; HEPATIC CYSTS; NEOPLASMS; SCLEROTHERAPY; INJECTION; ABLATION; ALCOHOL; LESIONS; ASPIRATION; TUMORS AB Background: Surgery for pancreatic cysts is associated with significant morbidity. A pilot study previously demonstrated the safety of EUS-guided ethanol lavage of pancreatic cysts. Objective: To determine whether EUS-guided ethanol lavage would decrease pancreatic cyst size more than saline solution lavage. Design: Prospective, Multicenter, randomized trial. Setting: Two tertiary referral hospitals in the United States. Patients: Patients referred For EUS with a 1- to 5-cm Unilocular pancreatic cyst were randomized to blinded ethanol or saline solution lavage. Three months later, the cyst diameter was remeasured by EUS, and a second unblinded ethanol lavage was performed. Interventions: EUS-guided pancreatic cyst lavage. Main Outcome Measurements: Cyst ablation based on size changes from follow-up EUS, CT, and histology of resected specimens. Results: Of 58 patients randomized, 16 were excluded and 42 underwent initial ethanol (n = 25) or saline solution (n = 17) lavage. Ethanol lavage resulted in a greater mean percentage of decrease in Cyst surface area (-42.9; 95% CI, -58.4 to -27.4) compared with saline Solution alone (-11.4; 95% CI, -25.0 to 2.2; P = .009). Nineteen (76.0%) of 25 and 14 (82.3%) of 17 patients randomized to ethanol and saline solution, respectively, underwent a second ethanol lavage. A follow-up CT scan demonstrated resolution in 12 (33.3%) of 36 cysts. Histology of 4 resected cysts demonstrated epithelial ablation ranging from 0% (saline Solution alone) to 50% to 100% (1 or 2 ethanol lavages). Complication rates were similar in all groups. Limitation: Short-term follow-up. Conclusions: EUS-guided ethanol lavage results in a greater decrease in pancreatic cyst size compared With saline solution lavage with a similar safety profile. Overall CT-defined complete pancreatic cyst ablation was 33.3%. (This study is registered at ClinicalTrials.gov, identifier NCT00233038.) (Gastrointest Endosc 2009;70:710-23.) C1 [DeWitt, John] Indiana Univ, Med Ctr, Div Gastroenterol & Hepatol, Dept Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Schmidt, Christian M.] Indiana Univ, Med Ctr, Dept Surg, Indianapolis, IN 46202 USA. [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP DeWitt, J (reprint author), Indiana Univ, Med Ctr, Div Gastroenterol & Hepatol, Dept Gastroenterol & Hepatol, 550 N Univ Blvd,UH 4100, Indianapolis, IN 46202 USA. EM jodewitt@iupui.edu FU American Society for Gastrointestinal Endoscopy Research FX The following author received research support for this study from an American Society for Gastrointestinal Endoscopy Research and Outcomes and Effectiveness grant. NR 26 TC 76 Z9 80 U1 0 U2 3 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 OCT PY 2009 VL 70 IS 4 BP 710 EP 723 DI 10.1016/j.gie.2009.03.1173 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 503IM UT WOS:000270527300017 PM 19577745 ER PT J AU Willingham, FF Gee, DW Sylla, P Kambadakone, A Singh, AH Sahani, D Mino-Kenudson, M Rattner, DW Brugge, WR AF Willingham, Field F. Gee, Denise W. Sylla, Patricia Kambadakone, Avinash Singh, Anand H. Sahani, Dushyant Mino-Kenudson, Mari Rattner, David W. Brugge, William R. TI Natural orifice versus conventional laparoscopic distal pancreatectomy in a porcine model: a randomized, controlled trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT American-Society-for-Gastrointestinal-Endoscopy Postgraduate Course/Digestive Disease Week CY MAY 17-22, 2008 CL San Diego, CA SP Amer Soc Gastrointestinal Endoscopy ID NOTES SURVIVAL; FEASIBILITY; FREQUENCY; RESECTION; SURGERY; CLOSURE AB Background: Natural orifice transluminal endoscopic surgery (NOTES) research has primarily involved case series reports of low-risk procedures. Distal pancreatectomy has significant postoperative morbidity and Would permit rigorous examination in a controlled trial setting. Objective: To compare endoscopic transgastric distal pancreatectomy (ETDP) and laparoscopic distal pancreatectomy (LDP). Design: Prospective, randomized, controlled trial. Setting: Academic hospital. Subjects: Forty-one swine, 28 block randomized. Interventions: LDP was performed with 3 trocars and stapled transection of the pancreas. FTDP was performed via a gastrotomy, with 1 trocar for visualization, by using endoloop placement, snare transection, and purse-string gastrotomy closure. Main Outcome Measurements: Clinical examination, CT, serum chemistries, necropsy, peritoneal fluid analysis, and histologic examination. Results: Swine were survived for 8 days. The procedure time for ETDP was significantly greater than for LDP (1:52 vs 0:33 [hours: minutes]; P = .00). Pancreatic specimen weight was similar (4.1 g vs 5.5 g; P = .108). Postoperatively, 26 of 28 animals thrived. In the LDP group, 1 death caused by pancreatic leak and renal failure occured on day 1. In the ETDP group, 1 death caused by pneumothorax occurred intraoperatively. The necropsy, CT, and histologic examinations revealed focal resection-margin necrosis in 3 to 7 swine in the ETDP group with no proximal necrosis or pancreatitis. The groups were equivalent clinically, by survival, and by serum and peritoneal fluid analysis. The gastrotomy closure was associated with small serosal adhesions, but no gross abscess or necrosis. Limitation: Animal study. Conclusions: In the largest controlled trial of NOTES orifice surgery to date, there was no clinical or survival difference between NOTES and laparoscopic approaches. (Gastrointest Endosc 2009;70:740-7.) C1 [Willingham, Field F.; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA USA. [Gee, Denise W.; Sylla, Patricia; Rattner, David W.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kambadakone, Avinash; Singh, Anand H.; Sahani, Dushyant] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Brugge, WR (reprint author), 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM Wbrugge@partners.org OI Willingham, Field/0000-0002-7071-3001 NR 24 TC 18 Z9 19 U1 0 U2 1 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 OCT PY 2009 VL 70 IS 4 BP 740 EP 747 DI 10.1016/j.gie.2009.03.021 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 503IM UT WOS:000270527300020 PM 19560766 ER PT J AU Hetz, C Thielen, P Matus, S Nassif, M Court, F Kiffin, R Martinez, G Cuervo, AM Brown, RH Glimcher, LH AF Hetz, Claudio Thielen, Peter Matus, Soledad Nassif, Melissa Court, Felipe Kiffin, Roberta Martinez, Gabriela Cuervo, Ana Maria Brown, Robert H. Glimcher, Laurie H. TI XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy SO GENES & DEVELOPMENT LA English DT Article DE Amyotrophic lateral sclerosis; unfolded protein response; endoplasmic reticulum stress; XBP-1; autophagy ID ENDOPLASMIC-RETICULUM STRESS; MUTANT SUPEROXIDE-DISMUTASE; TRANSCRIPTION FACTOR XBP-1; ER STRESS; TRANSGENIC MICE; MOTOR-NEURONS; UP-REGULATION; DISEASE; ALS; NEURODEGENERATION AB Mutations in superoxide dismutase-1 (SOD1) cause familial amyotrophic lateral sclerosis (fALS). Recent evidence implicates adaptive responses to endoplasmic reticulum (ER) stress in the disease process via a pathway known as the unfolded protein response (UPR). Here, we investigated the contribution to fALS of X-box-binding protein-1 (XBP-1), a key UPR transcription factor that regulates genes involved in protein folding and quality control. Despite expectations that XBP-1 deficiency would enhance the pathogenesis of mutant SOD1, we observed a dramatic decrease in its toxicity due to an enhanced clearance of mutant SOD1 aggregates by macroautophagy, a cellular pathway involved in lysosome-mediated protein degradation. To validate these observations in vivo, we generated mutant SOD1 transgenic mice with specific deletion of XBP-1 in the nervous system. XBP-1-deficient mice were more resistant to developing disease, correlating with increased levels of autophagy in motoneurons and reduced accumulation of mutant SOD1 aggregates in the spinal cord. Post-mortem spinal cord samples from patients with sporadic ALS and fALS displayed a marked activation of both the UPR and autophagy. Our results reveal a new function of XBP-1 in the control of autophagy and indicate critical cross-talk between these two signaling pathways that can provide protection against neurodegeneration. C1 [Hetz, Claudio; Thielen, Peter; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Hetz, Claudio; Matus, Soledad; Nassif, Melissa; Martinez, Gabriela] Univ Chile, Inst Biomed Sci, FONDAP Ctr Mol Studies Cell, Santiago, Chile. [Hetz, Claudio; Matus, Soledad; Nassif, Melissa; Martinez, Gabriela] Univ Chile, Millennium Nucleus Neural Morphogenesis, Santiago, Chile. [Court, Felipe] Pontificia Univ Catolica Chile, Fac Biol Sci, Dept Physiol, Santiago, Chile. [Kiffin, Roberta; Cuervo, Ana Maria] Albert Einstein Coll Med, Inst Aging Studies, Bronx, NY 10461 USA. [Brown, Robert H.] Massachusetts Gen Hosp East, Day Neuromuscular Res Lab, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM chetz@med.uchile.cl; lglimche@hsph.harvard.edu RI Hetz, Claudio/I-1900-2013; Court, Felipe/C-5911-2015 OI Hetz, Claudio/0000-0001-7724-1767; FU Leila Y Mathers Charitable Foundation; NIH [AI32412]; Genzyme Sponsor Research Agreement; FONDECYT [1070444, 3085017, 1070377, AG031782]; FONDAP [15010006]; Millennium Nucleus [P07-048-F]; Muscular Dystrophy Association; Michael J. Fox Foundation for Parkinson's Research; National Parkinson Foundation; High Q Foundation; ICGEB; ALSA-The Milton Safenowitz Post-Doctoral; CONICYT Ph. D; National Institute of Neurological Disorders and Stroke; National Institute on Aging; Al-Athel ALS Research Foundation; ALS Association; ALS Therapy Alliance; Angel Fund; Project ALS; Pierre L de Bourgknecht ALS Research Foundation FX We thank Drs. Fabio Martinon, Sebastian Bernales, and Sergio Lavandero for helpful discussion, and Benjamin Caballero and Sylvia Flores for technical assistance. We thank Dianne AnneMarie Wills (MD) for organizing tissue transfer from the ALS tissue bank, Patricia Boya and Maria Luisa Colombo for advice about autophagy assays, and Drs. Noburo Mizushima and Tamotsu Yoshimori for providing LC3-EGFP and LC3-RFP-EGFP constructs. We are grateful to Drs. Julie Atkin and Bradley Turner for kindly providing expression vectors for mutant and wild-type SOD1-EGFP, and Dr. Nir Hacohen and The Broad Institute for providing shRNA lentiviral constructs. We thank Dr. Ron Kopito for providing the GFPu expression vector, and Dr. Nico Dantuma for providing the CD3-YFP vector. This work was supported by the V. Harold and Leila Y Mathers Charitable Foundation and NIH grant AI32412 (to L. H. G.); Genzyme Sponsor Research Agreement, FONDECYT number 1070444, FONDAP grant number 15010006, Millennium Nucleus number P07-048-F, The Muscular Dystrophy Association, The Michael J. Fox Foundation for Parkinson's Research, National Parkinson Foundation, High Q Foundation, and ICGEB (to C. H.); FONDECYT number 3085017 and ALSA-The Milton Safenowitz Post-Doctoral Fellowship for ALS Research (to S. M.); CONICYT Ph. D. fellowship (to M. N. and G. M.); National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the Al-Athel ALS Research Foundation, the ALS Association, the ALS Therapy Alliance, the Angel Fund, Project ALS, and the Pierre L de Bourgknecht ALS Research Foundation (to R. H. B.); FONDECYT number 1070377 (to (F. C.); and grant AG031782 (to A. M. C.). NR 48 TC 240 Z9 246 U1 7 U2 27 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 OCT PY 2009 VL 23 IS 19 BP 2294 EP 2306 DI 10.1101/gad.1830709 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 501NW UT WOS:000270389600007 PM 19762508 ER PT J AU Durst, R Neumark, Y Meiner, V Friedlander, Y Sharon, N Polak, A Beeri, R Danenberg, H Erez, G Spitzen, S Ben-Avi, L Leitersdorf, E Lotan, C AF Durst, Ronen Neumark, Yehuda Meiner, Vardiella Friedlander, Yechiel Sharon, Nir Polak, Arthur Beeri, Ronen Danenberg, Haim Erez, Gilli Spitzen, Shoshi Ben-Avi, Liat Leitersdorf, Eran Lotan, Chaim TI Increased Risk for Atherosclerosis of Various Macrophage Scavenger Receptor 1 Alleles SO GENETIC TESTING AND MOLECULAR BIOMARKERS LA English DT Article ID CORONARY-ARTERY-DISEASE; PROSTATE-CANCER RISK; SEQUENCE VARIANTS; OVEREXPRESSION; SUSCEPTIBILITY; POPULATIONS; CD36; GENE; MICE AB Aims: Macrophage scavenger receptor 1 (MSR1) mediates the uptake of modified low density lipoprotein (LDL)-cholesterol. The significance of MSR1 in atherosclerosis development in animal models is uncertain. In this study we sought to determine the significance of MSR1 polymorphisms in its encoding gene in susceptibility to atherosclerosis. Methods: We genotyped three polymorphic sites in the MSR1 gene including a 3-bp "TTA" insertion-deletion in intron 7 (rs3036811, Indel 7), an intron 5 SNP (rs33959637, IVS5-59), and a missense coding single nucleotide polymorphism (SNP) in exon 6 (rs3747531, P275A) in 136 nondiabetic Ashkenazi men under age 55 years (mean = 47.3 +/- 4.8 years) undergoing coronary angiography. Assessment of coronary disease was done by the number of segments with stenosis greater than 20% (coronary artery narrowing greater than 20% [CAGE > 20%]), greater than 50% (CAGE > 50%), and total number of diseased vessels. Linear regression modeling was used to define associations between atherosclerotic burden and MSR1 SNPs and haplotypes. Results: Significant associations were noted between IVS5-59 and number of diseased vessels (p = 0.009) and CAGE > 20% (p = 0.017), which remained significant upon controlling for age, cholesterol level, hypertension, and smoking. Conclusion: This study demonstrates an association between MSR1 polymorphisms and atherosclerosis, suggesting that atherosclerotic risk associated with classic risk factors may be modified by MSR1 polymorphisms. These findings point to a significant role of MSR1 in atherosclerosis. C1 [Durst, Ronen; Polak, Arthur; Beeri, Ronen; Danenberg, Haim; Lotan, Chaim] Hadassah Hebrew Univ, Med Ctr, Dept Cardiol, Jerusalem, Israel. [Neumark, Yehuda] Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Braun Sch Publ Hlth & Community Med, Jerusalem, Israel. [Meiner, Vardiella; Friedlander, Yechiel; Sharon, Nir] Hadassah Hebrew Univ, Med Ctr, Dept Human Genet, Jerusalem, Israel. [Erez, Gilli; Spitzen, Shoshi; Ben-Avi, Liat; Leitersdorf, Eran] Hadassah Hebrew Univ, Med Ctr, Dept Med B, Jerusalem, Israel. RP Durst, R (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 2, Boston, MA 02114 USA. EM rdurst@partners.org FU Young Investigators; Faculty of Medicine, Hebrew University-Hadassah,; Women's Health Award from the Hadassah Medical Organization; Massachusetts General Hospital Cardiology Department FX We thank Dr. Aaron Baggish from the Massachusetts General Hospital Cardiology Department for his kind remarks. NR 19 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1945-0265 J9 GENET TEST MOL BIOMA JI Genet. Test. Mol. Biomark. PD OCT PY 2009 VL 13 IS 5 BP 583 EP 587 DI 10.1089/gtmb.2009.0048 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 504FO UT WOS:000270601500006 PM 19715475 ER PT J AU Lipstein, EA Perrin, JM Waisbren, SE Prosser, LA AF Lipstein, Ellen A. Perrin, James M. Waisbren, Susan E. Prosser, Lisa A. TI Impact of false-positive newborn metabolic screening results on early health care utilization SO GENETICS IN MEDICINE LA English DT Article DE health services utilization; neonatal screening; false-positive results; metabolic diseases; genetic diseases ID TANDEM MASS-SPECTROMETRY; PEDIATRIC RESIDENTS; COST-EFFECTIVENESS; CYSTIC-FIBROSIS; COMMUNICATION; PARENTS; DISORDERS; STRESS; TESTS AB Purpose: To analyze the association between false-positive newborn screening results and health care utilization. Methods: We surveyed parents regarding their children's health care utilization. Parents of children who received false-positive newborn screening results were primarily enrolled by a screening laboratory in Pennsylvania. Parents of children with normal results were recruited through the Massachusetts birth registry. We used bivariate tests and multivariate regression to assess the association between newborn screening results and primary care utilization, emergency room use, and hospitalization by the age of 6 months. Results: Our sample included 200 children with false-positive results and 137 with normal results. Variation in recruitment strategies led to sample children with false-positive results being more likely to be non-white, have unmarried parents, and be of lower socioeconomic status. After adjusting for significant covariates, such as age, race, and socioeconomic status, there were no significant associations between newborn screening results and child health care utilization. Conclusions: Despite the reported negative psychosocial effects of false-positive results, our study found no impact on early health care utilization. These results may assist in economic analyses of newborn screening as they suggest that medical costs associated with false-positive results are limited to the cost of diagnostic testing and follow-up, Genet Med 2009:11(10):716-721. C1 [Lipstein, Ellen A.; Perrin, James M.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Waisbren, Susan E.] Childrens Hosp, Metab Program, Boston, MA 02115 USA. [Prosser, Lisa A.] Univ Michigan Hlth Syst, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI USA. [Prosser, Lisa A.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Ctr Child Hlth Care Studies, Boston, MA USA. [Prosser, Lisa A.] Harvard Pilgrim Hlth Care, Boston, MA USA. RP Lipstein, EA (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM elipstein@partners.org FU Maternal and Child Health Bureau [5H46 MC00158]; National Institutes of Health [RO1 HG02085]; Health Resources and Services Administration [T32 HP10018] FX Presented in part at the Pediatric Academic Societies Meeting, Baltimore, Maryland on May 5, 2009. The authors acknowledge Dionne Graham, PhD, for her statistical assistance and the many parents who participated in this study. NR 34 TC 17 Z9 17 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2009 VL 11 IS 10 BP 716 EP 721 DI 10.1097/GIM.0b013e3181b3a61e PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 515EK UT WOS:000271449800005 PM 19661808 ER PT J AU Lau, NC Robine, N Martin, R Chung, WJ Niki, Y Berezikov, E Lai, EC AF Lau, Nelson C. Robine, Nicolas Martin, Raquel Chung, Wei-Jen Niki, Yuzo Berezikov, Eugene Lai, Eric C. TI Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line SO GENOME RESEARCH LA English DT Article ID PIWI-INTERACTING RNAS; HYBRID DYSGENESIS; MOLECULAR-BASIS; SOMATIC-CELLS; STEM-CELLS; MELANOGASTER; GERMLINE; EVOLUTION; FLAMENCO; ENCODES AB Piwi proteins, a subclass of Argonaute-family proteins, carry similar to 24-30-nt Piwi-interacting RNAs (piRNAs) that mediate gonadal defense against transposable elements (TEs). We analyzed the Drosophila ovary somatic sheet (OSS) cell line and found that it expresses miRNAs, endogenous small interfering RNAs (endo-siRNAs), and piRNAs in abundance. In contrast to intact gonads, which contain mixtures of germline and somatic cell types that express different Piwi-class proteins, OSS cells are a homogenous somatic cell population that expresses only PIWI and primary piRNAs. Detailed examination of its TE-derived piRNAs and endo-siRNAs revealed aspects of TE defense that do not rely upon ping-pong amplification. In particular, we provide evidence that a subset of piRNA master clusters, including flamenco, are specifically expressed in OSS and ovarian follicle cells. These data indicate that the restriction of certain TEs in somatic gonadal cells is largely mediated by a primary piRNA pathway. C1 [Lau, Nelson C.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lau, Nelson C.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Robine, Nicolas; Martin, Raquel; Chung, Wei-Jen; Lai, Eric C.] Sloan Kettering Inst, Dept Dev Biol, New York, NY 10065 USA. [Niki, Yuzo] Ibaraki Univ, Dept Sci, Mito, Ibaraki 3108512, Japan. [Berezikov, Eugene] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. [Berezikov, Eugene] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. RP Lau, NC (reprint author), Brandeis Univ, Dept Biol, 415 South St, Waltham, MA 02454 USA. EM nlau@brandeis.edu; laie@mskcc.org RI Berezikov, Eugene/D-3363-2013 OI Berezikov, Eugene/0000-0002-1145-2884 FU National Institute of Child Health and Human Development [K99-HD057298-01]; Sidney Kimmel Cancer Foundation; Alfred Bressler Scholars Fund; US National Institutes of Health [R01-GM083300, U01-HG004261] FX We thank Martha Reed and Liz Perkins for help with fly extract; Mark Borowsky for assistance with the Illumina GA-II system; Vladimir Kapitonov for helpful discussions; and Gregory Hannon, Mikiko Siomi, and Haruhiko Siomi for generous gifts of antibodies. We thank Robert Kingston for his support during this project. N. C. L. was funded by the National Institute of Child Health and Human Development (K99-HD057298-01). Work in E. C. L.'s group was supported by the Sidney Kimmel Cancer Foundation, the Alfred Bressler Scholars Fund, and the US National Institutes of Health (R01-GM083300 and U01-HG004261). NR 48 TC 114 Z9 123 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2009 VL 19 IS 10 BP 1776 EP 1785 DI 10.1101/gr.094896.109 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 501NX UT WOS:000270389700010 PM 19541914 ER PT J AU Smith, AM Heisler, LE Mellor, J Kaper, F Thompson, MJ Chee, M Roth, FP Giaever, G Nislow, C AF Smith, Andrew M. Heisler, Lawrence E. Mellor, Joseph Kaper, Fiona Thompson, Michael J. Chee, Mark Roth, Frederick P. Giaever, Guri Nislow, Corey TI Quantitative phenotyping via deep barcode sequencing SO GENOME RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DELETION MUTANTS; YEAST; GENOME; LIBRARY; UNIQUE; GENES AB Next-generation DNA sequencing technologies have revolutionized diverse genomics applications, including de novo genome sequencing, SNP detection, chromatin immunoprecipitation, and transcriptome analysis. Here we apply deep sequencing to genome-scale fitness profiling to evaluate yeast strain collections in parallel. This method, Barcode analysis by Sequencing, or "Bar-seq," outperforms the current benchmark barcode microarray assay in terms of both dynamic range and throughput. When applied to a complex chemogenomic assay, Bar-seq quantitatively identifies drug targets, with performance superior to the benchmark microarray assay. We also show that Bar-seq is well-suited for a multiplex format. We completely re-sequenced and re-annotated the yeast deletion collection using deep sequencing, found that similar to 20% of the barcodes and common priming sequences varied from expectation, and used this revised list of barcode sequences to improve data quality. Together, this new assay and analysis routine provide a deep-sequencing-based toolkit for identifying gene-environment interactions on a genome-wide scale. C1 [Smith, Andrew M.; Giaever, Guri; Nislow, Corey] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Smith, Andrew M.; Nislow, Corey] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada. [Smith, Andrew M.; Heisler, Lawrence E.; Giaever, Guri; Nislow, Corey] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. [Heisler, Lawrence E.; Giaever, Guri] Univ Toronto, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, Canada. [Mellor, Joseph; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Mellor, Joseph; Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Kaper, Fiona; Thompson, Michael J.; Chee, Mark] Prognosys Biosci Inc, La Jolla, CA 92037 USA. RP Giaever, G (reprint author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada. EM ggiaever@gmail.com; corey.nislow@gmail.com RI Smith, Andrew/C-1253-2009; Giaever, Guri/D-3930-2009; Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X; Nislow, Corey/0000-0002-4016-8874 FU US National Institutes of Health (NIH) [R01 HG003224, R21 HG004756, HG003788]; NIH/NHGRI; CIHR [MOP-81340, MOP-84305]; NHGRI [HG00317-05] FX This work was supported by US National Institutes of Health (NIH) grants R01 HG003224 and R21 HG004756 to F. P. R. and HG003788 to M. C. J. M. was supported by an individual NRSA Fellowship from the NIH/NHGRI. G. G. and C. N. were supported by the CIHR (MOP-81340 to G. G., MOP-84305 to C. N.) and the NHGRI (HG00317-05). We thank Angela Chu, Bob P. St. Onge, and all members of the HIP-HOP lab for advice; and Lixin Zhou for developing NGS analysis methods at Prognosys Biosciences. We thank Ron Davis and all members of the YKO consortium. NR 21 TC 117 Z9 119 U1 2 U2 19 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2009 VL 19 IS 10 BP 1836 EP 1842 DI 10.1101/gr.093955.109 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 501NX UT WOS:000270389700016 PM 19622793 ER PT J AU Markson, G Kiel, C Hyde, R Brown, S Charalabous, P Bremm, A Semple, J Woodsmith, J Duley, S Salehi-Ashtiani, K Vidal, M Komander, D Serrano, L Lehner, P Sanderson, CM AF Markson, Gabriel Kiel, Christina Hyde, Russell Brown, Stephanie Charalabous, Panagoula Bremm, Anja Semple, Jennifer Woodsmith, Jonathan Duley, Simon Salehi-Ashtiani, Kourosh Vidal, Marc Komander, David Serrano, Luis Lehner, Paul Sanderson, Christopher M. TI Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network SO GENOME RESEARCH LA English DT Article ID FORCE-FIELD; RING DOMAIN; DEGRADATION; SIGNALS; LIGASE; UBIQUITYLATION; PREDICTION; STABILITY; COMPLEX; SYSTEM AB In eukaryotic cells the stability and function of many proteins are regulated by the addition of ubiquitin or ubiquitin-like peptides. This process is dependent upon the sequential action of an E1-activating enzyme, an E2-conjugating enzyme, and an E3 ligase. Different combinations of these proteins confer substrate specificity and the form of protein modification. However, combinatorial preferences within ubiquitination networks remain unclear. In this study, yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions. These data include 535 experimentally defined novel E2/E3-RING interactions and >1300 E2/E3-RING pairs with more favorable predicted free-energy values than the canonical UBE2L3-CBL complex. The significance of Y2H predictions was assessed by both mutagenesis and functional assays. Significantly, 74/80 (>92%) of Y2H predicted complexes were disrupted by point mutations that inhibit verified E2/E3-RING interactions, and a similar to 93% correlation was observed between Y2H data and the functional activity of E2/E3-RING complexes in vitro. Analysis of the high-density human E2/E3-RING network reveals complex combinatorial interactions and a strong potential for functional redundancy, especially within E2 families that have undergone evolutionary expansion. Finally, a one-step extended human E2/E3-RING network, containing 2644 proteins and 5087 edges, was assembled to provide a resource for future functional investigations. C1 [Hyde, Russell; Charalabous, Panagoula; Woodsmith, Jonathan; Sanderson, Christopher M.] Univ Liverpool, Sch Biomed Sci, Dept Physiol, Liverpool L69 3BX, Merseyside, England. [Markson, Gabriel; Brown, Stephanie; Duley, Simon; Lehner, Paul] Univ Cambridge, Cambridge Inst Med Res, Dept Med, Cambridge CB2 0XY, England. [Kiel, Christina; Semple, Jennifer; Serrano, Luis] UPF, ICREA Ctr Regulacio Genom, Barcelona 08003, Spain. [Kiel, Christina; Semple, Jennifer; Serrano, Luis] UPF, EMBL CRG Syst Biol Res Unit, Barcelona 08003, Spain. [Bremm, Anja; Komander, David] MRC, Lab Mol Biol Prot & Nucle Acid Chem, Cambridge CB2 0QH, England. [Salehi-Ashtiani, Kourosh; Vidal, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Salehi-Ashtiani, Kourosh; Vidal, Marc] Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. [Salehi-Ashtiani, Kourosh; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Serrano, Luis] Inst Catalana Recerca & Estudis Avancats, ICREA, Barcelona 08003, Spain. [Serrano, Luis] Inst Catalana Recerca & Estudis Avancats, EMBL CRG Syst Biol Res Unit, Barcelona 08003, Spain. RP Sanderson, CM (reprint author), Univ Liverpool, Sch Biomed Sci, Dept Physiol, Liverpool L69 3BX, Merseyside, England. EM c.sanderson@liv.ac.uk RI Serrano, Luis/B-3355-2013; Semple, Jennifer/K-4782-2014; OI Serrano, Luis/0000-0002-5276-1392; Semple, Jennifer/0000-0001-7221-9560; Salehi-Ashtiani, Kourosh/0000-0002-6521-5243; Bremm, Anja/0000-0003-1386-0926 FU U. K. Medical Research Council; Wellcome Trust; U. S. National Human Genome Research Institute [2R01HG001715]; Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium); EU (INTERACTION PROTEOME) [LSHG-CT-2003-505520] FX We acknowledge Phil James for the donation of yeast strains PJ694a and PJ69-4 alpha and the pGAD vector. We are also grateful to David Markie for providing the pGBAD-B, pACTBD-B, and pACTBE-B vectors, which were invaluable for our studies, and to Philip Cohen for E2 enzymes and expression constructs used in functional assays. The work described in this manuscript was in part funded by the U. K. Medical Research Council and the Wellcome Trust. K. S-A. and M. V. were supported by a gift from the Ellison Foundation and a grant from the U. S. National Human Genome Research Institute (2R01HG001715) to M. V. M. V. is a "Chercheur Qualifie Honoraire" from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). Work performed by C. K. and L. S. was supported by EU grant number LSHG-CT-2003-505520 (INTERACTION PROTEOME). NR 29 TC 86 Z9 87 U1 1 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 2009 VL 19 IS 10 BP 1905 EP 1911 DI 10.1101/gr.093963.109 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 501NX UT WOS:000270389700023 PM 19549727 ER PT J AU Grant, MD Kremen, W Franz, C Panizzon, MS Toomey, R Karlinsky, J Murray, R Lyons, M AF Grant, M. D. Kremen, W. Franz, C. Panizzon, M. S. Toomey, R. Karlinsky, J. Murray, R. Lyons, M. TI GENETIC AND ENVIRONMENTAL INFLUENCES ON PULMONARY FUNCTION IN A MIDDLE-AGED TWIN COHORT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Karlinsky, J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Kremen, W.; Franz, C.] Univ Calif San Diego, Ctr Behav Genom, San Diego, CA 92103 USA. [Karlinsky, J.] VA Boston Healthcare, Boston, MA USA. RI Lyons, Michael/B-6119-2011 NR 0 TC 0 Z9 0 U1 1 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 9 EP 9 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900035 ER PT J AU Byers, AL Bruce, ML Yaffe, K AF Byers, A. L. Bruce, M. L. Yaffe, K. TI PREVALENCE AND CORRELATES OF SUICIDALITY IN COMMUNITY-DWELLING OLDER ADULTS: THE NATIONAL COMORBIDITY SURVEY REPLICATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Byers, A. L.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Byers, A. L.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Bruce, M. L.] Weill Cornell Med Coll, White Plains, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900188 ER PT J AU Karel, MJ AF Karel, M. J. TI THOUGHTS ON MENTORING PREDOCTORAL PSYCHOLOGY INTERNS AND POSTDOCTORAL FELLOWS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Karel, M. J.] VA Boston Healthcare Syst, Brockton, MA USA. [Karel, M. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 43 EP 43 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900194 ER PT J AU Clemens, P Sae-Chew, P Niizawa, G AF Clemens, P. Sae-Chew, P. Niizawa, G. TI MOLECULAR PATHOGENESIS OF AND NOVEL TREATMENT APPROACHES TO CANCER CACHEXIA IN MURINE MODELS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Clemens, P.; Sae-Chew, P.; Niizawa, G.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Clemens, P.; Sae-Chew, P.; Niizawa, G.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 64 EP 65 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900305 ER PT J AU Bamman, MM AF Bamman, M. M. TI ROLE OF SATELLITE CELLS IN AGE-RELATED MUSCLE REGENERATION IMPAIRMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bamman, M. M.] Birmingham VA Med Ctr, GRECC & Physiol & Biophys, Birmingham, AL USA. [Bamman, M. M.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 65 EP 65 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900307 ER PT J AU Leggett, AN Zarit, SH Duda, JE Galvin, JE Kaufer, DI Lippa, CF Taylor, A AF Leggett, A. N. Zarit, S. H. Duda, J. E. Galvin, J. E. Kaufer, D. I. Lippa, C. F. Taylor, A. TI ROLE STRAIN, PERSONAL STRAIN, AND WORRY ABOUT PERFORMANCE AMONG CAREGIVERS OF PEOPLE WITH LEWY BODY DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Leggett, A. N.; Zarit, S. H.] Penn State Univ, State Coll, PA USA. [Duda, J. E.] Univ Penn, Philadelphia, PA 19104 USA. [Duda, J. E.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Galvin, J. E.] Washington Univ, St Louis, MO USA. [Kaufer, D. I.] Univ N Carolina, Chapel Hill, NC USA. [Lippa, C. F.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Taylor, A.] Lewy Body Dementia Assoc, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 80 EP 80 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900377 ER PT J AU Weston, AL Costa, P Simonsick, E Ayonayon, HN Harris, T Rosano, C Satterfield, S Yaffe, K AF Weston, A. L. Costa, P. Simonsick, E. Ayonayon, H. N. Harris, T. Rosano, C. Satterfield, S. Yaffe, K. TI THE ASSOCIATION OF PERSONALITY DOMAINS AND COGNITIVE FUNCTION: FINDINGS FROM THE HEALTH ABC STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Weston, A. L.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Costa, P.; Simonsick, E.; Harris, T.] NIA, Baltimore, MD 21224 USA. [Rosano, C.] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Satterfield, S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Weston, A. L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ayonayon, H. N.; Yaffe, K.] Univ Calif San Francisco Epidemiol & Biostat, San Francisco, CA USA. [Yaffe, K.] Univ Calif San Francisco Neurol, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 92 EP 92 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900433 ER PT J AU Beverly, EA Ritholz, MD Leighton, A Weinger, K AF Beverly, E. A. Ritholz, M. D. Leighton, A. Weinger, K. TI AGE DIFFERENCES IN ATTITUDES AND BELIEFS IN TYPE 2 DIABETES MANAGEMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Beverly, E. A.; Ritholz, M. D.; Leighton, A.; Weinger, K.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, E. A.; Ritholz, M. D.; Weinger, K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 157 EP 157 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900741 ER PT J AU Espinoza, S Jung, I Hazuda, H AF Espinoza, S. Jung, I. Hazuda, H. TI IS THERE AN ETHNIC DISPARITY IN MORTALITY BETWEEN OLDER MEXICAN AMERICANS AND EUROPEAN AMERICANS? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Espinoza, S.; Jung, I.; Hazuda, H.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Espinoza, S.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 166 EP 166 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900785 ER PT J AU Crowe, M Clay, OJ Sartori, AC Wadley, VG Andel, R Sawyer, P Allman, R AF Crowe, M. Clay, O. J. Sartori, A. C. Wadley, V. G. Andel, R. Sawyer, P. Allman, R. TI DIABETES AND COGNITIVE DECLINE IN OLDER AFRICAN AMERICANS AND WHITES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wadley, V. G.; Sawyer, P.; Allman, R.] Univ Alabama, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Allman, R.] Birmingham VA Med Ctr, Birmingham, AL USA. [Andel, R.] Univ S Florida, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 192 EP 192 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900908 ER PT J AU Clay, OJ Crowe, M Crowther, M Sawyer, P Allman, R AF Clay, O. J. Crowe, M. Crowther, M. Sawyer, P. Allman, R. TI USE OF THE GERIATRIC DEPRESSION SCALE IN AFRICAN AMERICAN AND CAUCASIAN MEDICARE BENEFICIARIES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Clay, O. J.; Crowe, M.] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. [Crowther, M.] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. [Sawyer, P.; Allman, R.] UAB, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Allman, R.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 235 EP 235 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100142 ER PT J AU Faulkner, K Studenski, S Scheier, M Morse, J Coday, M Simonsick, E Yaffe, K Cauley, JA AF Faulkner, K. Studenski, S. Scheier, M. Morse, J. Coday, M. Simonsick, E. Yaffe, K. Cauley, J. A. TI DOES CONSCIENTIOUSNESS PROTECT AGAINST RECURRING FALLS IN OLDER MEN? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Faulkner, K.; Studenski, S.; Morse, J.; Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Scheier, M.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Coday, M.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Simonsick, E.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 1 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 244 EP 244 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100188 ER PT J AU Roberge, BJ Mahoney, E Chuang, S Minaker, K AF Roberge, B. J. Mahoney, E. Chuang, S. Minaker, K. TI A RANDOMIZED CONTROL TRIAL OF A NURSING COMMUNICATION INTERVENTION TRANSITIONING INTO THE HOSPITAL SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Roberge, B. J.; Mahoney, E.] Massachusetts Gen Hosp, Yvonne Munn Ctr Nursing Res, Boston, MA 02114 USA. [Minaker, K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chuang, S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Mahoney, E.] Boston Coll, William F Connell Sch Nursing, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 248 EP 248 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100207 ER PT J AU White, AR Snow, A Kunik, ME Beck, C Karner, T AF White, A. R. Snow, A. Kunik, M. E. Beck, C. Karner, T. TI BARRIERS TO PAIN MANAGEMENT FOR PERSONS WITH SEVERE DEMENTIA IN THE NURSING HOME SO GERONTOLOGIST LA English DT Meeting Abstract C1 [White, A. R.] Birmingham VA Med Ctr, Birmingham, AL USA. [White, A. R.] Univ Alabama, Birmingham, AL USA. [Snow, A.] Univ Alabama, Tuscaloosa, AL USA. [Snow, A.] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Karner, T.] Univ Houston, Houston, TX USA. [Kunik, M. E.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Snow, A.; Kunik, M. E.] Baylor Coll Med, Houston, TX 77030 USA. [Beck, C.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 267 EP 267 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100296 ER PT J AU Buracchio, T Mattek, NC Hayes, T Kaye, J AF Buracchio, T. Mattek, N. C. Hayes, T. Kaye, J. TI WALKING CHARACTERISTICS ON THE 5 DAYS BEFORE AND AFTER A FALL: NO HARM, NO FOUL, NO CHANGE? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Buracchio, T.; Mattek, N. C.; Hayes, T.; Kaye, J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Buracchio, T.; Kaye, J.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 274 EP 275 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100330 ER PT J AU Wray, LA Chiu, C Lacoe, CL Beverly, E AF Wray, L. A. Chiu, C. Lacoe, C. L. Beverly, E. TI EDUCATION, HEALTH, AND DISABILITY IN OLDER AGE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wray, L. A.; Chiu, C.; Lacoe, C. L.] Penn State, Biobehav Hlth, University Pk, PA USA. [Beverly, E.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 284 EP 284 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100373 ER PT J AU Harvath, TA Young, HM Lee, L AF Harvath, T. A. Young, H. M. Lee, L. TI POST-MASTERS CERTIFICATE OPTION IN ADVANCED PRACTICE GERONTOLOGICAL NURSING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Harvath, T. A.] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. [Lee, L.] Portland VA Med Ctr, Portland, OR USA. [Young, H. M.] Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 316 EP 316 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100528 ER PT J AU Mlinac, M Sheeran, T Lees, F Saint, J AF Mlinac, M. Sheeran, T. Lees, F. Saint, J. TI USING COACHING CALLS TO PROMOTE ACTIVE MAINTENANCE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mlinac, M.] VA Boston Healthcare Syst, Boston, MA USA. [Sheeran, T.; Lees, F.; Saint, J.] Univ Rhode Isl, Kingston, RI 02881 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 329 EP 329 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100596 ER PT J AU Riebe, D Blissmer, B Greaney, M AF Riebe, D. Blissmer, B. Greaney, M. TI FACTORS PREDICTING THE MAINTENANCE OF PHYSICAL ACTIVITY: RESULTS FROM THE SENIOR PROJECT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Riebe, D.; Blissmer, B.] Univ Rhode Isl, Kingston, RI 02881 USA. [Greaney, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Greaney, M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 329 EP 329 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100594 ER PT J AU Leveille, SG Hausdorff, J Herman, T Milberg, W Giladi, N AF Leveille, S. G. Hausdorff, J. Herman, T. Milberg, W. Giladi, N. TI CHRONIC PAIN, EXECUTIVE FUNCTION, AND DUAL TASK MOBILITY IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Leveille, S. G.; Hausdorff, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Leveille, S. G.; Hausdorff, J.; Milberg, W.] Harvard Univ, Sch Med, Boston, MA USA. [Hausdorff, J.; Herman, T.; Giladi, N.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Milberg, W.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 334 EP 334 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100616 ER PT J AU Azar, AR Cho, LY Chopra, MP AF Azar, A. R. Cho, L. Y. Chopra, M. P. TI VASCULAR RISK AND MAJOR DEPRESSION IN OLDER PRIMARY CARE PATIENTS RECEIVING MENTAL HEALTH TREATMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Azar, A. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Azar, A. R.; Cho, L. Y.; Chopra, M. P.] VA Boston Healthcare Syst, Boston, MA USA. [Azar, A. R.; Cho, L. Y.; Chopra, M. P.] Harvard Univ, Sch Med, Boston, MA USA. [Cho, L. Y.; Chopra, M. P.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 355 EP 355 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100718 ER PT J AU Mroczek, D Stawski, RS Almeida, D Spiro, A Turiano, N AF Mroczek, D. Stawski, R. S. Almeida, D. Spiro, A. Turiano, N. TI AFFECT VARIABILITY PREDICTS MORTALITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mroczek, D.; Turiano, N.] Purdue Univ, W Lafayette, IN 47907 USA. [Stawski, R. S.; Almeida, D.] Penn State Univ, State Coll, PA USA. [Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 355 EP 356 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100721 ER PT J AU Cadet, T Maramaldi, P AF Cadet, T. Maramaldi, P. TI PATIENT-PROVIDER COMMUNICATION: HISPANIC ELDERS AND COLORECTAL CANCER SCREENING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cadet, T.; Maramaldi, P.] Simmons Coll, Boston, MA 02115 USA. [Maramaldi, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maramaldi, P.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 392 EP 392 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UK UT WOS:000271794100906 ER PT J AU Huang, A Moore, E Boyko, E Scholes, D Lin, F Vittinghoff, E Fihn, S AF Huang, A. Moore, E. Boyko, E. Scholes, D. Lin, F. Vittinghoff, E. Fihn, S. TI VAGINAL ATROPHY SYMPTOMS: NATURAL HISTORY AND PREDICTORS IN OLDER WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Huang, A.; Lin, F.; Vittinghoff, E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Moore, E.] Royal Childrens Hosp, Parkville, Vic 3052, Australia. [Boyko, E.] Univ Washington, Seattle, WA 98195 USA. [Boyko, E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Scholes, D.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Fihn, S.] Dept Vet Affairs, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 420 EP 420 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200069 ER PT J AU Wieland, G Boland, R Kinosian, B AF Wieland, G. Boland, R. Kinosian, B. TI THE PROGRAM OF ALL-INCLUSIVE CARE FOR THE ELDERLY [PACE]: LENGTH OF ENROLLMENT [LOE] AND REASONS FOR DISENROLLMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wieland, G.; Boland, R.] Palmetto Hlth Richland, Geriatr Serv, Columbia, SC USA. [Kinosian, B.] CHERP, Philadelphia, PA USA. [Wieland, G.] Univ S Carolina, Sch Med, Columbia, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 425 EP 425 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200092 ER PT J AU Williams, BR Sawyer, P Allman, R AF Williams, B. R. Sawyer, P. Allman, R. TI TIL DEATH DO US PART: SOCIODEMOGRAPHIC, HEALTH AND FUNCTION CORRELATES OF TIME SINCE SPOUSAL LOSS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Williams, B. R.; Sawyer, P.; Allman, R.] UAB, Birmingham, AL USA. [Williams, B. R.; Allman, R.] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 437 EP 438 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200149 ER PT J AU Archambault, E Schuster, J Karel, MJ Trevino, K Salib, B Doughan, J Moye, J AF Archambault, E. Schuster, J. Karel, M. J. Trevino, K. Salib, B. Doughan, J. Moye, J. TI REACTING AND ADAPTING: CANCER SURVIVORSHIP IN VETERANS ACROSS THE LIFESPAN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Archambault, E.; Schuster, J.; Karel, M. J.; Trevino, K.; Salib, B.; Moye, J.] VA Boston Healthcare Syst, Boston, MA USA. [Doughan, J.] VA San Francisco Healthcare Syst, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 472 EP 472 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200319 ER PT J AU Mavandadi, S Oslin, DW AF Mavandadi, S. Oslin, D. W. TI SOCIAL EXCHANGES AND SUICIDAL IDEATION AMONG OLDER VETERANS WITH BEHAVIORAL HEALTH ISSUES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mavandadi, S.; Oslin, D. W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Oslin, D. W.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 486 EP 486 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200382 ER PT J AU Kramer, B Vivrette, R Martin, J Rubenstein, LZ AF Kramer, B. Vivrette, R. Martin, J. Rubenstein, L. Z. TI DEVELOPMENT OF A FALL RISK SELF-ASSESSMENT FOR SENIORS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, B.; Vivrette, R.; Martin, J.; Rubenstein, L. Z.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Kramer, B.; Martin, J.; Rubenstein, L. Z.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kramer, B.; Rubenstein, L. Z.] Fall Prevent Ctr Excellence, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 497 EP 497 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200432 ER PT J AU Espinoza, S Pierce, A Shamsi, K Halade, D Richardson, A AF Espinoza, S. Pierce, A. Shamsi, K. Halade, D. Richardson, A. TI A COMPARATIVE GLYCOPROTEOMICS APPROACH TO FRAILTY USING LECTIN AFFINITY CHROMATOGRAPHY: A PILOT STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Espinoza, S.; Pierce, A.; Shamsi, K.; Halade, D.; Richardson, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Espinoza, S.; Pierce, A.; Richardson, A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RI Pierce, Anson/D-1079-2012 OI Pierce, Anson/0000-0002-1383-0180 NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 499 EP 499 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200439 ER PT J AU Hanlon, JT Castle, N Stone, RA Handler, S Semla, T Pugh, M Berlowitz, D Dysken, M AF Hanlon, J. T. Castle, N. Stone, R. A. Handler, S. Semla, T. Pugh, M. Berlowitz, D. Dysken, M. TI POTENTIAL UNDERUSE OF ANTIDEPRESSANTS IN OLDER VETERAN NURSING HOME PATIENTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hanlon, J. T.; Castle, N.; Stone, R. A.; Handler, S.] UPITT, Pittsburgh, PA USA. [Hanlon, J. T.; Stone, R. A.; Handler, S.] Pittsburgh VA, Pittsburgh, PA USA. [Pugh, M.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Semla, T.] VA PBM, Hines, IL USA. [Berlowitz, D.] Edith Nourse Rogers VA Mem Hospital, Bedford, MA USA. [Dysken, M.] Minneapolis VA, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 BP 500 EP 500 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UL UT WOS:000271794200443 ER PT J AU Bhide, P AF Bhide, P. TI NEUROVASCULAR INTERACTIONS IN THE EMBRYONIC BRAIN SO GLIA LA English DT Meeting Abstract CT 9th European Meeting on Glial Cells in Health and Disease CY SEP 08-12, 2009 CL Paris, FRANCE C1 [Bhide, P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD OCT PY 2009 VL 57 IS 13 BP S5 EP S5 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 497QK UT WOS:000270075500021 ER PT J AU Huillard, E Mehta, S Kesari, S Alberta, JA Kane, M Stiles, CD Rowitch, DH AF Huillard, E. Mehta, S. Kesari, S. Alberta, J. A. Kane, M. Stiles, C. D. Rowitch, D. H. TI ROLES FOR THE BHLH TRANSCRIPTION FACTOR OLIG2 IN GLIOMA SO GLIA LA English DT Meeting Abstract CT 9th European Meeting on Glial Cells in Health and Disease CY SEP 08-12, 2009 CL Paris, FRANCE C1 [Huillard, E.; Rowitch, D. H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mehta, S.; Kesari, S.; Alberta, J. A.; Kane, M.; Stiles, C. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD OCT PY 2009 VL 57 IS 13 BP S165 EP S165 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 497QK UT WOS:000270075500678 ER PT J AU Maire, C Olausson, KH Ling, J Haynes, R Learner, E Ligon, KL AF Maire, C. Olausson, Holmberg K. Ling, J. Haynes, R. Learner, E. Ligon, K. L. TI PROM1 (CD133) IS A MARKER OF DISTRIBUTED GLIAL PROGENITORS IN THE ADULT BRAIN SO GLIA LA English DT Meeting Abstract CT 9th European Meeting on Glial Cells in Health and Disease CY SEP 08-12, 2009 CL Paris, FRANCE C1 [Haynes, R.] Harvard Univ, Childrens Hosp, Dept Pathol & Neurol, Boston, MA 02115 USA. [Ligon, K. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD OCT PY 2009 VL 57 IS 13 BP S78 EP S78 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 497QK UT WOS:000270075500322 ER PT J AU Rist, JM Shadrach, JL Wagers, AJ Franklin, RJM AF Rist, J. M. Shadrach, J. L. Wagers, A. J. Franklin, R. J. M. TI REJUVENATING REMYELINATION IN THE AGEING CNS SO GLIA LA English DT Meeting Abstract CT 9th European Meeting on Glial Cells in Health and Disease CY SEP 08-12, 2009 CL Paris, FRANCE C1 [Rist, J. M.; Franklin, R. J. M.] Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge, England. [Rist, J. M.; Franklin, R. J. M.] Univ Cambridge, Dept Vet Med, Cambridge, England. [Shadrach, J. L.; Wagers, A. J.] Harvard Univ, Joslin Diabet Ctr, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Shadrach, J. L.; Wagers, A. J.] Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD OCT PY 2009 VL 57 IS 13 BP S159 EP S159 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 497QK UT WOS:000270075500652 ER PT J AU Russell, AH AF Russell, Anthony H. TI Forwards Through the Rear-View Mirror SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; RISK ENDOMETRIAL CANCER; ADJUVANT RADIOTHERAPY; INTERMEDIATE-RISK; CARCINOMA; CHEMOTHERAPY; IRRADIATION; EFFICACY C1 [Russell, Anthony H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Russell, Anthony H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Russell, AH (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM AHRUSSELL@PARTNERS.ORG NR 15 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2009 VL 115 IS 1 BP 1 EP 3 DI 10.1016/j.ygyno.2009.08.001 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 496IZ UT WOS:000269965700001 PM 19716938 ER PT J AU Folkins, AK Saleemuddin, A Garrett, LA Garber, JE Muto, MG Tworoger, SS Crum, CP AF Folkins, Ann K. Saleemuddin, Aasia Garrett, Leslie A. Garber, Judy E. Muto, Michael G. Tworoger, Shelley S. Crum, Christopher P. TI Epidemiologic correlates of ovarian cortical inclusion cysts (CICs) support a dual precursor pathway to pelvic epithelial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Cortical inclusions; Mullerian; Endosalpingiosis; Tubal ligation ID BODY-MASS-INDEX; RISK-FACTORS; SEROUS CARCINOMA; BRCA MUTATIONS; 1ST BIRTH; TUMORS; WOMEN; AGE; OOPHORECTOMIES; POPULATION AB Objective. Many ovarian carcinomas are presumed to arise within ovarian cortical inclusion cysts (CICs). This study examined the frequency of ovarian CICs in relation to epidemiologic risk factors in women with BRCA1 and BRCA2 (BRCA+) mutations. Methods. BRCA+ women who underwent risk-reducing bilateral salpingo-oophorectomy were studied (n = 74). Fifteen demographic variables (e.g., age at time of surgery, age at first birth, age at menopause, body mass index (BMI), gravidity) from a review of the medical records and three pathologic variables (cystic and atretic follicles, corpora lutea) were recorded. Statistical associations were made using T-test or Chi Square analysis and logistic regression analysis for p-trend. Results. Women whose ovaries contained 7 for more CICs were older at first birth (p = 0.034), surgery (p = 0.059), menopause (p = 0.046) and had a higher BMI (p = 0.034) than those with <7 CICs. Regression analysis revealed a significant association between CICs and increasing BMI (p = 0.01). Conclusions. CICs correlate with greater body mass index, similar to low-grade serous and endometrioid tumors and in contrast to high-grade serous carcinoma and its putative precursor in the fallopian tube. A model is presented for ovarian and tubal pathways to pelvic cancer that are linked to different microscopic precursors with distinct epidemiologic correlates. (C) 2009 Elsevier Inc. All rights reserved. C1 [Folkins, Ann K.; Saleemuddin, Aasia; Crum, Christopher P.] Brigham & Womens Hosp, Div Womens, Boston, MA 02115 USA. [Folkins, Ann K.; Saleemuddin, Aasia; Crum, Christopher P.] Brigham & Womens Hosp, Dept Pathol, Div Perinatal Pathol, Boston, MA 02115 USA. [Garber, Judy E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Tworoger, Shelley S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Tworoger, Shelley S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Div Womens, Amory 3-127,75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org OI Tworoger, Shelley/0000-0002-6986-7046 FU NCI [P50CA10500, IR21CA124688-01A1]; Division of Women's and Perinatal Pathology; Brigham and Women's Hospital FX This work was supported by grants from the NCI (P50CA10500 [SPORE]: D. Cramer, PI), NCI IR21CA124688-01A1 (CP Crum, PI), The Columbia Hospital For Women Research Foundation (CPCrurn, PI), the Francis Ward Paine and TSA Pemberton Funds from the Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, and a gift in memory of Elizabeth Ford Smith. NR 32 TC 8 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2009 VL 115 IS 1 BP 108 EP 111 DI 10.1016/j.ygyno.2009.06.032 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 496IZ UT WOS:000269965700021 PM 19615727 ER PT J AU Boruta, DM Gehrig, PA Fader, AN Olawaiye, AB AF Boruta, David M., II Gehrig, Paola A. Fader, Amanda Nickles Olawaiye, Alexander B. TI Management of women with uterine papillary serous cancer: A Society of Gynecologic Oncology (SGO) review SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Uterine papillary serous carcinoma; Endometrial cancer; Staging; Radiotherapy; Chemotherapy ID ADVANCED ENDOMETRIAL CARCINOMA; PLATINUM-BASED CHEMOTHERAPY; PHASE-III TRIAL; DOXORUBICIN PLUS CISPLATIN; CLEAR-CELL CARCINOMA; WHOLE ABDOMINOPELVIC RADIATION; PREOPERATIVE SERUM CA-125; POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION PROFILES; IN-SITU HYBRIDIZATION AB Objective. Uterine papillary serous carcinoma (UPSC) is a clinically and pathologically distinct subtype of endometrial cancer. Although less common than its endometrioid carcinoma (EEC) counterpart, UPSC accounts for a disproportionate number of endometrial cancer related deaths. To date, limited prospective trials exist from which evidence-based management can be developed. This review summarizes the available literature concerning UPSC in an effort to provide the clinician with information pertinent to its management. Methods. MEDLINE was searched for all research articles published in English between January 1, 1966 and May 1, 2009 in which the studied population included women diagnosed with UPSC. Although preference was given to prospective studies, studies were not limited by design or by numbers of subjects given the paucity of available reports. Results. UPSC is morphologically and genetically different from EEC. Women often present with postmenopausal vaginal bleeding, but may also present with abnormal cervical cytology, ascites, or a pelvic mass. In some cases, the diagnosis may be made with endometrial biopsy, while in other cases it is not made until the time of definitive surgery. Metastatic disease is common and best identified via comprehensive surgical staging. Local and distant recurrences occur frequently, with extra-pelvic relapses reported most commonly. Optimal cytoreduction and adjuvant platinum/taxane-based chemotherapy appear to improve survival, while adjuvant radiotherapy may contribute to loco-regional disease control. Conclusions. Women diagnosed with UPSC should undergo comprehensive surgical staging and an attempt at optimal cytoreduction. Platinum/taxane-based adjuvant chemotherapy should be considered in the treatment of both early- and advanced-stage patients. Careful long-term surveillance is indicated as many of these women will recur. Prospective clinical trials of women with UPSC are necessary in order to delineate the optimal therapy for women with newly diagnosed and recurrent disease. (C) 2009 Elsevier Inc. All rights reserved. C1 [Boruta, David M., II] Massachusetts Gen Hosp, Yawkey Ctr, Gillette Ctr Gynecol Oncol,Div Gynecol Oncol, Vincent Obstet & Gynecol Serv,Dept Obstet & Repro, Boston, MA 02114 USA. [Gehrig, Paola A.] Univ N Carolina, Dept Obstet & Gynecol, Div Gynecol Oncol, Chapel Hill, NC 27599 USA. [Fader, Amanda Nickles] Cleveland Clin Fdn, Div Gynecol Oncol, Dept Obstet & Gynecol, Cleveland, OH 44195 USA. [Olawaiye, Alexander B.] Univ Pittsburgh, Magee Womens Hosp, Med Ctr,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Gillette Ctr Gynecol Oncol,Div Gynecol Oncol, Vincent Obstet & Gynecol Serv,Dept Obstet & Repro, Suite 9E,55 Fruit St, Boston, MA 02114 USA. EM dboruta@partners.org NR 147 TC 101 Z9 101 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2009 VL 115 IS 1 BP 142 EP 153 DI 10.1016/j.ygyno.2009.06.011 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 496IZ UT WOS:000269965700028 PM 19592079 ER PT J AU Parthan, A Posner, MR Brammer, C Beltran, P Jansen, JP AF Parthan, Anju Posner, Marshall R. Brammer, Caroline Beltran, Philippe Jansen, Jeroen P. TI COST UTILITY OF DOCETAXEL AS INDUCTION CHEMOTHERAPY FOLLOWED BY CHEMORADIATION IN LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE induction docetaxel; cost-effectiveness head and neck cancer; induction TPF ID CANCER; CISPLATIN; FLUOROURACIL AB Background. Trial TAX 324 showed that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (TPF) compared with cisplatin and 5-fluorouracil (PF) followed by chemoradiation increases survival and time to progression in squamous cell carcinoma of head and neck (SCCHN). Methods. A Markov model was developed to estimate the cost-effectiveness of induction chemotherapy with docetaxel in the United Kingdom from the payer perspective. Health states were based on the WHO criteria for objective response to cancer treatments. Efficacy and safety data were obtained from the trial. Resource utilization, costs, and utility data were primarily derived from the literature. Results. A patient on TPF gained 4.1 quality adjusted life years (QALYs) versus 2.0 GALYs for PF patient, Corresponding lifetime costs were 32,440 pound and 28,718 pound. The cost per QALY gained for TPF versus PF was 1782 pound, Conclusions. TPF is cost-effective as induction chemotherapy in locally advanced SCCHN compared with PF Local treatment patterns may impact findings for other countries. (C) 2009 Wiley Periodicals, Inc. Head Neck 31: 1255-1262, 2009 C1 [Parthan, Anju; Jansen, Jeroen P.] Mapi Values, Boston, MA 02114 USA. [Posner, Marshall R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Brammer, Caroline] New Cross Hosp, Wolverhampton, England. [Beltran, Philippe] Sanofi Aventis, Paris, France. RP Jansen, JP (reprint author), Mapi Values, 133 Portland St, Boston, MA 02114 USA. EM jeroenjansen@mapivalues.com FU Sanofi-Aventis FX Contract grant sponsor: Sanofi-Aventis. NR 17 TC 20 Z9 20 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2009 VL 31 IS 10 BP 1255 EP 1262 DI 10.1002/hed.21096 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 506KE UT WOS:000270772900001 PM 19731394 ER PT J AU Truong, MT Kamat, UR Liebsch, NJ Curry, WT Lin, DT Barker, FG Loeffler, JS Chan, AW AF Truong, Minh Tam Kamat, Urmila R. Liebsch, Norbert J. Curry, William T. Lin, Derrick T. Barker, Fred G., II Loeffler, Jay S. Chan, Annie W. TI PROTON RADIATION THERAPY FOR PRIMARY SPHENOID SINUS MALIGNANCIES: TREATMENT OUTCOME AND PROGNOSTIC FACTORS SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE sphenoid sinus; paranasal sinus malignancies; skull-based malignancies; proton radiation therapy; craniofacial resection; radiation; staging; prognostic factors ID ANTERIOR SKULL BASE; CRANIOFACIAL RESECTION; NASAL CAVITY; PARANASAL SINUSES; FRACTIONATED RADIATION; TUMORS; CANCER; SURGERY; RADIOTHERAPY; EXPERIENCE AB Background. The purpose of this study was to determine treatment outcome and prognostic factors in patients with locally advanced primary sphenoid sinus malignancy treated with proton radiation therapy. Methods. Between 1991 and 2005, 20 patients with primary sphenoid sinus malignancy received proton beam to a median dose of 76 Gray equivalent. Results. With a median follow-up of 27 months, the 2-year local, regional, and freedom from distant metastasis rates were 86%, 86%, and 50%, respectively. The disease-free and overall-survival rates at 2 years were 31% and 53%, respectively. In multivariate analysis, oropharyngeal involvement (p=.005) and anterior cranial fossa invasion (p=.02) were predictive for poor disease-free survival rate. Brain invasion was predictive for decreased overall-survival rate (p=.05). Conclusions. Proton radiation therapy results in excellent local control in patients with advanced primary sphenoid sinus malignancy. Brain invasion, involvement of the oropharynx and anterior cranial fossa are important prognostic factors. (C) 2009 Wiley Periodicals, Inc. Head Neck 31: 1297-1308, 2009 C1 [Truong, Minh Tam; Kamat, Urmila R.; Liebsch, Norbert J.; Loeffler, Jay S.; Chan, Annie W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Truong, Minh Tam; Kamat, Urmila R.; Liebsch, Norbert J.; Curry, William T.; Lin, Derrick T.; Barker, Fred G., II; Loeffler, Jay S.; Chan, Annie W.] Harvard Univ, Sch Med, Boston, MA USA. [Truong, Minh Tam] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. [Curry, William T.; Barker, Fred G., II] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Truong, MT (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM mttruong@partners.org FU National Institute of Health [NCI-PO1-CA21239] FX Contract grant sponsor: National Institute of Health; contract grant number: NCI-PO1-CA21239. NR 28 TC 26 Z9 28 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2009 VL 31 IS 10 BP 1297 EP 1308 DI 10.1002/hed.21092 PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 506KE UT WOS:000270772900006 PM 19536762 ER PT J AU Singer, SJ Falwell, A Gaba, DM Meterko, M Rosen, A Hartmann, CW Baker, L AF Singer, Sara J. Falwell, Alyson Gaba, David M. Meterko, Mark Rosen, Amy Hartmann, Christine W. Baker, Laurence TI Identifying organizational cultures that promote patient safety SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE hospital characteristics; organizational culture; patient safety; safety climate; survey ID TOTAL-QUALITY-MANAGEMENT; HEALTH-CARE; MEDICATION ERRORS; CLIMATE; HOSPITALS; IMPACT; MODEL; INTERVENTION; SATISFACTION; PERCEPTIONS AB Background: Safety climate refers to shared perceptions of what an organization is like with regard to safety, whereas safety culture refers to employees' fundamental ideology and orientation and explains why safety is pursued in the manner exhibited within a particular organization. Although research has sought to identify opportunities for improving safety outcomes by studying patterns of variation in safety climate, few empirical studies have examined the impact of organizational characteristics such as culture on hospital safety climate. Purpose: This study explored how aspects of general organizational culture relate to hospital patient safety climate. Methodology: In a stratified sample of 92 U.S. hospitals, we sampled 100% of senior managers and physicians and 10% of other hospital workers. The Patient Safety Climate in Healthcare Organizations and the Zammuto and Krakower organizational culture surveys measured safety climate and group, entrepreneurial, hierarchical, and production orientation of hospitals' culture, respectively. We administered safety climate surveys to 18,361 personnel and organizational culture surveys to a 5,894 random subsample between March 2004 and May 2005. Secondary data came from the 2004 American Hospital Association Annual Hospital Survey and Dun & Bradstreet. Hierarchical linear regressions assessed relationships between organizational culture and safety climate measures. Findings: Aspects of general organizational culture were strongly related to safety climate. A higher level of group culture correlated with a higher level of safety climate, but more hierarchical culture was associated with lower safety climate. Aspects of organizational culture accounted for more than threefold improvement in measures of model fit compared with models with controls alone. A mix of culture types, emphasizing group culture, seemed optimal for safety climate. Practice Implications: Safety climate and organizational culture are positively related. Results support strategies that promote group orientation and reduced hierarchy, including use of multidisciplinary team training, continuous quality improvement tools, and human resource practices and policies. C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Falwell, Alyson] Altos Grp, Oakland, CA USA. [Gaba, David M.] VA Palo Alto Hlth Care Syst, Patient Safety Culture Inst, Palo Alto, CA USA. [Meterko, Mark] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Rosen, Amy; Hartmann, Christine W.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Baker, Laurence] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM ssinger@hsph.harvard.edu OI Baker, Laurence/0000-0001-5032-794X FU AHRQ HHS [R01 HS013920] NR 45 TC 61 Z9 62 U1 5 U2 39 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD OCT-DEC PY 2009 VL 34 IS 4 BP 300 EP 311 PG 12 WC Health Policy & Services SC Health Care Sciences & Services GA 507KS UT WOS:000270852700002 PM 19858915 ER PT J AU Chapko, MK Liu, CF Perkins, M Li, YF Fortney, JC Maciejewski, ML AF Chapko, Michael K. Liu, Chuan-Fen Perkins, Mark Li, Yu-Fang Fortney, John C. Maciejewski, Matthew L. TI EQUIVALENCE OF TWO HEALTHCARE COSTING METHODS: BOTTOM-UP AND TOP-DOWN SO HEALTH ECONOMICS LA English DT Article DE economics; cost; measurement; activity-based costing; relative value units ID DECISION-SUPPORT-SYSTEM; AVERAGE COST; VA; EXPENDITURES; AGREEMENT; HOSPITALS; STAYS AB This paper compares two quite different approaches to estimating costs: a 'bottom-up' approach. represented by the US Department of Veterans Affairs' (VA) Decision Support System that uses local costs of specific inputs; and a 'top-down' approach, represented by the costing system created by the VA Health Economics Resource Center. which assigns the VA national healthcare budget to specific products using various weighting systems. Total annual costs per patient plus the cost for specific services (e.g. clinic visit, radiograph, laboratory, inpatient admission) were compared using scatterplots, correlations. mean difference, and standard deviation of individual differences. Analysis are based upon 2001 costs for 14915 patients at 72 facilities. Correlations ranged from 0.24 for the cost of outpatient encounters to 0.77 for the cost of inpatient admissions. and 0.85 for total annual cost. The mean difference between costing methods was $707 ($4168 versus $3461) for total annual cost. The standard deviation of the individual differences was $5934. Overall, the agreement between the two costing systems varied by the specific cost being measured and increased with aggregation. Administrators and researchers conducting cost analyses need to carefully consider the purpose, methods, characteristics, strengths. and weaknesses when selecting a method for assessing cost. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Chapko, Michael K.; Liu, Chuan-Fen; Perkins, Mark; Li, Yu-Fang] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Chapko, Michael K.; Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Li, Yu-Fang] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Fortney, John C.] Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev, Ctr Mental Hlth & Outcomes Res, N Little Rock, AR USA. [Fortney, John C.] Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, Coll Med, Little Rock, AR 72205 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. RP Chapko, MK (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, 1660 S Columbian Way, Seattle, WA 98108 USA. EM michael.chapko@va.gov FU Health Services Research and Development Services; Department of Veterans Affairs [IIR 20-005]; Department of Veterans Affairs; University of Washington; University of Arkansas for Medical Sciences; University of North Carolina FX This study was funded by Health Services Research and Development Services, Department of Veterans Affairs (IIR 20-005). The views expressed herein are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the University of Washington, the University of Arkansas for Medical Sciences, or the University of North Carolina. NR 29 TC 42 Z9 43 U1 2 U2 18 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD OCT PY 2009 VL 18 IS 10 BP 1188 EP 1201 DI 10.1002/hec.1422 PG 14 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 496BD UT WOS:000269942100007 PM 19097041 ER PT J AU Kagawa-Singer, M Emmons, KM AF Kagawa-Singer, Marjorie Emmons, Karen M. TI Behavioral Theory in a Diverse Society: Moving Our Field Forward SO HEALTH EDUCATION & BEHAVIOR LA English DT Editorial Material ID CANCER PREVENTION; HEALTH-PROMOTION; WORKING-CLASS; POPULATION; CHALLENGES; CENTERS; LESSONS; SCIENCE; NEED C1 [Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Asian Amer Studies Dept, Los Angeles, CA 90095 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kagawa-Singer, M (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, 650 Charles Young Dr S,Box 951772, Los Angeles, CA 90095 USA. EM mkagawa@ucla.edu FU PHS HHS [HHSN261200900383P] NR 25 TC 2 Z9 2 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2009 VL 36 BP 172S EP 176S DI 10.1177/1090198109340521 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 516ZJ UT WOS:000271581900015 PM 19830890 ER PT J AU Singer, SJ Hartmann, CW Hanchate, A Zhao, SB Meterko, M Shokeen, P Lin, ST Gaba, DM Rosen, AK AF Singer, Sara J. Hartmann, Christine W. Hanchate, Amresh Zhao, Shibei Meterko, Mark Shokeen, Priti Lin, Shoutzu Gaba, David M. Rosen, Amy K. TI Comparing Safety Climate between Two Populations of Hospitals in the United States SO HEALTH SERVICES RESEARCH LA English DT Article DE Safety culture; safety climate; survey research; hospitals; integrated hospital networks; decomposition ID PATIENT SAFETY; US HOSPITALS; HEALTH-CARE; CULTURE; NURSE; VALIDATION; PHYSICIANS; TEAMWORK; BEHAVIOR; OUTCOMES AB Objective To compare safety climate between diverse U.S. hospitals and Veterans Health Administration (VA) hospitals, and to explore the factors influencing climate in each setting. Data Sources Primary data from surveys of hospital personnel; secondary data from the American Hospital Association's 2004 Annual Survey of Hospitals. Study Design Cross-sectional study of 69 U.S. and 30 VA hospitals. Data Collection For each sample, hierarchical linear models used safety-climate scores as the dependent variable and respondent and facility characteristics as independent variables. Regression-based Oaxaca-Blinder decomposition examined differences in effects of model characteristics on safety climate between the U.S. and VA samples. Principal Findings The range in safety climate among U.S. and VA hospitals overlapped substantially. Characteristics of individuals influenced safety climate consistently across settings. Working in southern and urban facilities corresponded with worse safety climate among VA employees and better safety climate in the U.S. sample. Decomposition results predicted 1.4 percentage points better safety climate in U.S. than in VA hospitals: -0.77 attributable to sample-characteristic differences and 2.2 due to differential effects of sample characteristics. Conclusions Results suggest that safety climate is linked more to efforts of individual hospitals than to participation in a nationally integrated system or measured characteristics of workers and facilities. C1 [Singer, Sara J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Singer, Sara J.; Lin, Shoutzu; Gaba, David M.] Stanford Univ, Ctr Hlth Policy, Stanford, CA 94305 USA. [Singer, Sara J.; Lin, Shoutzu; Gaba, David M.] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Hartmann, Christine W.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Hartmann, Christine W.; Meterko, Mark; Rosen, Amy K.] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02215 USA. [Hanchate, Amresh] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Zhao, Shibei; Meterko, Mark; Shokeen, Priti; Rosen, Amy K.] Boston VA Med Ctr, Ctr Org Leadership & Management Res, Boston, MA USA. [Gaba, David M.] VA Palo Alto Hlth Care Syst, Patient Safety Culture Inst, Palo Alto, CA USA. RP Singer, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ssinger@hsph.harvard.edu OI Hanchate, Amresh/0000-0002-7038-4463 FU VA Health Services Research and Development Service [IIR 03-303-2] FX Joint Acknowledgment/Disclosure Statement: Financial support for this research was provided by the VA Health Services Research and Development Service grant no. IIR 03-303-2. The authors would also like to acknowledge research support from Ms. Alyson Falwell. NR 42 TC 16 Z9 16 U1 3 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2009 VL 44 IS 5 BP 1563 EP 1584 DI 10.1111/j.1475-6773.2009.00994.x PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 490IO UT WOS:000269494600008 PM 19619250 ER PT J AU Tsai, CL Clark, S Sullivan, AF Camargo, CA AF Tsai, Chu-Lin Clark, Sunday Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Development and Validation of a Risk-Adjustment Tool in Acute Asthma SO HEALTH SERVICES RESEARCH LA English DT Article DE Asthma; emergency department; hospital admission; profiling; risk adjustment ID 30-DAY MORTALITY-RATES; EMERGENCY-DEPARTMENT; PROSPECTIVE MULTICENTER; MEASURING PERFORMANCE; HOSPITAL ADMISSION; EARLY PREDICTION; SETTING BUDGETS; UNITED-STATES; CARE; SURGERY AB Objective To develop and prospectively validate a risk-adjustment tool in acute asthma. Data Sources Data were obtained from two large studies on acute asthma, the Multicenter Airway Research Collaboration (MARC) and the National Emergency Department Safety Study (NEDSS) cohorts. Both studies involved > 60 emergency departments (EDs) and were performed during 1996-2001 and 2003-2006, respectively. Both included patients aged 18-54 years presenting to the ED with acute asthma. Study Design Retrospective cohort studies. Data Collection Clinical information was obtained from medical record review. The risk index was derived in the MARC cohort and then was prospectively validated in the NEDSS cohort. Principle Findings There were 3,515 patients in the derivation cohort and 3,986 in the validation cohort. The risk index included nine variables (age, sex, current smoker, ever admitted for asthma, ever intubated for asthma, duration of symptoms, respiratory rate, peak expiratory flow, and number of beta-agonist treatments) and showed satisfactory discrimination (area under the receiver operating characteristic curve, 0.75) and calibration ( p=.30 for Hosmer-Lemeshow test) when applied to the validation cohort. Conclusions We developed and validated a novel risk-adjustment tool in acute asthma. This tool can be used for health care provider profiling to identify outliers for quality improvement purposes. C1 [Tsai, Chu-Lin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,EMNet Coordinating Ctr, Boston, MA 02114 USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Tsai, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Critical Therapeutics (Lexington, MA); GlaxoSmithKline; Agency for Healthcare Research and Quality [R01 HS-13099]; [HL084401] FX Joint Acknowledgment/Disclosure Statement: This investigator-initiated study was supported by a research grant from Critical Therapeutics (Lexington, MA), but this funder had no role in data collection, statistical analysis, preparation of the manuscript, or decision to publish. The underlying studies were supported by unrestricted grants from GlaxoSmithKline ( Research Triangle Park, NC) and R01 HS-13099 from the Agency for Healthcare Research and Quality (Rockville, MD). Dr. Camargo was also funded by grant HL084401 ( Bethesda, MD). The authors thank the participating investigators for their ongoing dedication to emergency medicine and patient safety research ( full list in the online supplemental material). NR 40 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 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2009 VL 44 IS 5 BP 1701 EP 1717 DI 10.1111/j.1475-6773.2009.00998.x PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 490IO UT WOS:000269494600015 PM 19619246 ER PT J AU Larsen, E Liberman, MC AF Larsen, Erik Liberman, M. Charles TI Slow build-up of cochlear suppression during sustained contralateral noise: Central modulation of olivocochlear efferents? SO HEARING RESEARCH LA English DT Article DE Feedback; Inner ear; Brainstem plasticity; Olivocochlear reflex ID EVOKED OTOACOUSTIC EMISSIONS; AUDITORY-NERVE FIBERS; INDUCED HEARING-LOSS; OUTER HAIR-CELLS; ACOUSTIC INJURY; GUINEA-PIG; ELECTRICAL-STIMULATION; CENTRIFUGAL PATHWAYS; LOUD-SOUND; REFLEX AB The strength of the medial olivocochlear (OC) reflex is routinely assayed by measuring suppression of ipsilateral responses such as otoacoustic emissions (OAEs) by a brief contralateral noise, e.g., (Berlin, C.I., Hood, L.J., Cecola, P., Jackson, D.F., Szabo, P. 1993. Does type I afferent dysfunction reveal itself through lack of efferent suppression. Hear. Res. 65, 40-50). Here, we show in anesthetized guinea pigs, that the magnitude of OC-mediated suppression of ipsilateral cochlear responses (i.e., compound actions potentials (CAPs), distortion product (DP) OAEs and round-window noise) slowly builds over 2-3 min during a sustained contralateral noise. The magnitude of this build-up suppression was largest at low ipsilateral stimulus intensities, as seen for suppression measured at contra-noise onset. However, as a function of stimulus frequency, build-up suppression magnitude was complementary to onset suppression, i.e., largest at the lowest and highest frequencies tested. Both build-up and onset suppression were eliminated by cutting the OC bundle. In contrast to "slow effects" of shock-evoked medial OC activity (Sridhar, T.S., Liberman, M.C., Brown, M.C., Sewell, W.F. 1995. A novel cholinergic "slow effect" of efferent stimulation on cochlear potentials in the guinea pig. J. Neurosci. 15, 3667-3678), which are mediated by slow intracellular changes in Ca concentration in OHCs, build-up effects of contralateral noise are immediately extinguished upon OC bundle transection and are likely mediated by central modulation of the response rates in MOC fibers due to the sustained noise. Results suggest that conventional tests of OC reflex strength may underestimate its magnitude in noisy environments. (C) 2009 Elsevier B.V. All rights reserved. C1 [Larsen, Erik; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Larsen, Erik; Liberman, M. Charles] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM charles_liberman@meei.harvard.edu FU NIDCD [R01 (DC00188), P30 (DC05209), T32 DC00038] FX This work was supported by an R01 (DC00188) and a P30 (DC05209) from the NIDCD. E. Larsen was partly supported by a training grant from the NIDCD (T32 DC00038). This report is based on a thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Speech and Hearing Bioscience and Technology Program of the Harvard-MIT Division of Health Sciences and Technology. NR 56 TC 11 Z9 11 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 2009 VL 256 IS 1-2 BP 1 EP 10 DI 10.1016/j.heares.2009.02.002 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 502XV UT WOS:000270495000001 PM 19232534 ER PT J AU Singh, JP AF Singh, Jagmeet P. TI QRS configuration and cardiac resynchronization therapy: Do we need a patient-specific approach? SO HEART RHYTHM LA English DT Editorial Material ID BUNDLE-BRANCH BLOCK; LEFT-VENTRICULAR ACTIVATION; HEART-FAILURE; SYSTEM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Cardiac Arrhythmia Serv, GRB109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD OCT PY 2009 VL 6 IS 10 BP 1448 EP 1449 DI 10.1016/j.hrthm.2009.07.048 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 503AK UT WOS:000270502700010 PM 19968923 ER PT J AU Singh, JP Morady, F AF Singh, Jagmeet P. Morady, Fred TI Patient selection and classification for atrial fibrillation ablation: Thinking beyond duration SO HEART RHYTHM LA English DT Editorial Material DE Atrial fibrillation; Catheter ablation; Pulmonary vein isolation ID PULMONARY-VEIN ISOLATION; CONGESTIVE-HEART-FAILURE; CATHETER ABLATION; ANTIARRHYTHMIC-DRUGS; ANGIOTENSIN SYSTEM; RANDOMIZED-TRIAL; MODEL; MECHANISMS; CONDUCTION; SUBSTRATE C1 [Singh, Jagmeet P.] Harvard Univ, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp, Ctr Heart,Med Sch, Boston, MA 02114 USA. [Morady, Fred] Univ Michigan Hlth Syst, Ann Arbor, MI USA. RP Singh, JP (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp, Ctr Heart,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 40 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD OCT PY 2009 VL 6 IS 10 BP 1522 EP 1525 DI 10.1016/j.hrthm.2009.04.003 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 503AK UT WOS:000270502700026 PM 19695963 ER PT J AU DeAngelo, DJ AF DeAngelo, Daniel J. TI Nelarabine for the Treatment of Patients with Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Nelarabine; Compound 506078; Arranon; T-cell acute lymphoblastic leukemia; T-cell lymphoblastic lymphoma ID BONE-MARROW RELAPSE; ARABINOSYL-GUANINE; HEMATOLOGIC MALIGNANCIES; R-87 PROTOCOL; CYTO-TOXICITY; PHASE-II; GROUP-B; 9-BETA-D-ARABINOFURANOSYLGUANINE; ADULTS; DEOXYGUANOSINE AB Nelarabine (506U78) is a soluble prodrug of 9- Darabinofuranosylguanine (ara-G), a deoxyguanosine derivative. Nelarabine has significant activity in patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL). Principal toxicity is grade 3 or 4 neutropenia and thrombocytopenia. Neurologic toxicity with Guillain-Barre syndrome, depressed level of consciousness, and peripheral neuropathy are concerning side effects. Nelarabine is well tolerated and has significant antitumor activity in T-ALL and T-LBL. Nelarabine was approved by the Food and Drug Administration for patients with T-ALL/LBL who failed at least two prior regimens. Nelarabine is being explored in children and will be explored in the near future in adults with newly diagnosed T-ALL. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP DeAngelo, DJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ddeangelo@partners.org NR 34 TC 20 Z9 25 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2009 VL 23 IS 5 BP 1121 EP + DI 10.1016/j.hoc.2009.07.008 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 513KK UT WOS:000271321000011 PM 19825456 ER PT J AU Hoshida, Y Villanueva, A Sangiovanni, A Sole, M Gould, J Gupta, S Gabriel, S Peix, J Colombo, M Llovet, JM Golub, TR AF Hoshida, Yujin Villanueva, Augusto Sangiovanni, Angelo Sole, Manel Gould, Joshua Gupta, Supriya Gabriel, Stacey Peix, Judit Colombo, Massimo Llovet, Josep M. Golub, Todd R. TI GENE-EXPRESSION SIGNATURE PREDICTS OUTCOME OF LIVER CIRRHOSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Hoshida, Yujin; Gould, Joshua; Gupta, Supriya; Llovet, Josep M.; Golub, Todd R.] MIT, Broad Inst, Canc Program, Cambridge, MA 02139 USA. [Hoshida, Yujin; Gould, Joshua; Gupta, Supriya; Llovet, Josep M.; Golub, Todd R.] Harvard Univ, Cambridge, MA 02138 USA. [Hoshida, Yujin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Villanueva, Augusto; Sole, Manel; Gabriel, Stacey; Colombo, Massimo] Hosp Clin Barcelona, CIBERHED, IDIBAPS, BCLC Grp,HCC Translat Res Lab, Barcelona, Spain. [Sangiovanni, Angelo; Peix, Judit] Maggiore Hosp, IRCCS, FIRC Unit Liver Canc,Dept Gastroenterol & Endocri, AM & A Migliavacca Ctr Liver Dis, Milan, Italy. [Sangiovanni, Angelo; Peix, Judit] Univ Milan, Milan, Italy. [Colombo, Massimo] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Los Angeles, CA USA. [Llovet, Josep M.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 21 BP 312A EP 312A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000022 ER PT J AU Cutting, CC Harris, J Vedder, L North, TE Goessling, W AF Cutting, Claire C. Harris, James Vedder, Lea North, Trista E. Goessling, Wolfram TI ESTROGEN REGULATES LIVER DEVELOPMENT AND GROWTH VIA ESTROGEN RECEPTOR beta SIGNALING SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Cutting, Claire C.; Goessling, Wolfram] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Cutting, Claire C.; Goessling, Wolfram] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Cutting, Claire C.; Goessling, Wolfram] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cutting, Claire C.; Harris, James; Vedder, Lea; North, Trista E.; Goessling, Wolfram] Harvard Univ, Sch Med, Boston, MA USA. [Harris, James; Vedder, Lea; North, Trista E.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [North, Trista E.; Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 47 BP 324A EP 324A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000048 ER PT J AU Xu, J Verlinsky, A Lugea, A She, HY Mkrtchyan, H Ueno, A Cooper, M Tsukamoto, H AF Xu, Jun Verlinsky, Alla Lugea, Aurelia She, Hongyun Mkrtchyan, Hasmik Ueno, Akiko Cooper, Marcus Tsukamoto, Hidekazu TI MODERATE OBESITY AND ALCOHOL, TWO HITS ON MITOCHONDRIA AGGRAVATE STEATOHEPATITIS IN MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Xu, Jun; Verlinsky, Alla; She, Hongyun; Mkrtchyan, Hasmik; Ueno, Akiko; Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90033 USA. [Cooper, Marcus] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. [Lugea, Aurelia; Tsukamoto, Hidekazu] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 52 BP 326A EP 327A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000053 ER PT J AU Zhu, NL Wang, JH Lai, KK Asahina, K Tsukamoto, H AF Zhu, Nian-Ling Wang, Jiaohong Lai, Keane K. Asahina, Kinji Tsukamoto, Hidekazu TI NECDIN CROSS-TALKS WITH CANONICAL WNT AND SHH PATHWAYS AND CONTRIBUTES TO ANTI-ADIPOGENIC TRANS-DIFFERENTIATION OF HEPATIC STELLATE CELLS SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Zhu, Nian-Ling; Wang, Jiaohong; Lai, Keane K.; Asahina, Kinji; Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90033 USA. [Tsukamoto, Hidekazu] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 127 BP 364A EP 364A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000128 ER PT J AU Ryan, JC Lehil, M Kim, MS Duh, FM Martin, M George, S Kennedy, AE Yee, RM Tracy, D Cozen, M Carrington, M Monto, A AF Ryan, James C. Lehil, Mandeep Kim, Michael S. Duh, Fuh-Mei Martin, Maureen George, Sally Kennedy, Alan E. Yee, Russell M. Tracy, Daniel Cozen, Myrna Carrington, Mary Monto, Alexander TI NK CELL KIR CONTROL DIVERGENT OUTCOMES IN HEPATITIS C VIRUS INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ryan, James C.; Lehil, Mandeep; Kim, Michael S.; George, Sally; Kennedy, Alan E.; Yee, Russell M.; Tracy, Daniel; Cozen, Myrna; Monto, Alexander] San Francisco VA Med Ctr, San Francisco, CA USA. [Ryan, James C.; Kim, Michael S.; Cozen, Myrna; Monto, Alexander] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Duh, Fuh-Mei; Martin, Maureen; Carrington, Mary] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 176 BP 386A EP 386A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000177 ER PT J AU Vedvyas, C Sanders, C Yount, L Zheng, H Larson, AM Rutherford, AE Lee, WM Chung, R AF Vedvyas, Chetan Sanders, Corron Yount, Lindsay Zheng, Hui Larson, Anne M. Rutherford, Anna E. Lee, William M. Chung, Raymond TI CIRCULATING LEVELS OF THE HEPATOCYTE APOPTOSIS MARKER M-30 ARE PREDICTIVE OF OUTCOME IN NON-ACETAMINOPHEN ACUTE LIVER FAILURE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Vedvyas, Chetan; Chung, Raymond] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Yount, Lindsay; Rutherford, Anna E.] Brigham & Womens Hosp, GI Unit, Boston, MA 02115 USA. [Zheng, Hui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sanders, Corron; Larson, Anne M.; Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 260 BP 428A EP 428A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000261 ER PT J AU Yagi, H Soto-Gutierrez, A Uygun, B Izamis, ML Tompkins, RG Yarmush, ML Uygun, K AF Yagi, Hiroshi Soto-Gutierrez, Alejandro Uygun, Basak Izamis, Maria-Louisa Tompkins, Ronald G. Yarmush, Martin L. Uygun, Korkut TI ENGINEERING OF LIVER GRAFTS WITH DE/RECELLULARIZED NATIVE LIVER MATRICES FOR AUXILIARY TRANSPLANTATION SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 712 BP 638A EP 639A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000711 ER PT J AU Groessl, EJ Weingart, KR Gifford, AL Asch, S Ho, SB AF Groessl, Erik J. Weingart, Kimberly R. Gifford, Allen L. Asch, Steven Ho, Samuel B. TI SELF-MANAGEMENT INTERVENTIONS FOR VETERANS WITH HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Groessl, Erik J.; Weingart, Kimberly R.; Ho, Samuel B.] VA San Diego, HSR&D, San Diego, CA USA. [Groessl, Erik J.; Ho, Samuel B.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Asch, Steven] W Los Angeles VA, Los Angeles, CA USA. [Gifford, Allen L.] Bedford VA, Bedford, MA USA. [Gifford, Allen L.] Boston Univ, Boston, MA 02215 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 734 BP 648A EP 649A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000733 ER PT J AU Naugler, WE Sonnenberg, A AF Naugler, Willscott E. Sonnenberg, Amnon TI MODELS OF INFLUENCE IN CHRONIC LIVER DISEASE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Naugler, Willscott E.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Med GI & Hepatol, Portland, OR 97201 USA. [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 746 BP 654A EP 654A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000745 ER PT J AU Kim, AY Birch, CE Nagami, EH Bowen, MJ Lauer, GM McGovern, BH AF Kim, Arthur Y. Birch, Christopher E. Nagami, Ellen H. Bowen, Melinda J. Lauer, Georg M. McGovern, Barbara H. TI A SIMPLE STRATEGY TO SCREEN FOR ACUTE HCV INFECTION AMONG NEWLY INCARCERATED INJECTION DRUG USERS SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kim, Arthur Y.; Birch, Christopher E.; Nagami, Ellen H.; Bowen, Melinda J.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Lauer, Georg M.] Harvard Univ, Sch Med, Boston, MA USA. [Birch, Christopher E.; Nagami, Ellen H.; McGovern, Barbara H.] Lemuel Shattuck Hosp, Jamaica Plain, MA USA. [McGovern, Barbara H.] Tufts Med Sch, Boston, MA USA. [Kim, Arthur Y.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Bowen, Melinda J.] Univ Massachusetts, Sch Med, Worcester, MA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 777 BP 668A EP 668A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000776 ER PT J AU Sabharwal, S Corey, KE Mendez-Navarro, J Barlow, L Delgado-Borrego, AF Chung, R AF Sabharwal, Sabina Corey, Kathleen E. Mendez-Navarro, Jorge Barlow, Lydia Delgado-Borrego, Aymin F. Chung, Raymond TI CLEARANCE OF HCV IS ASSOCIATED WITH INCREASE IN SERUM ADIPONECTIN IN PATIENTS WITH HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sabharwal, Sabina; Corey, Kathleen E.; Mendez-Navarro, Jorge; Barlow, Lydia; Chung, Raymond] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delgado-Borrego, Aymin F.] Univ Miami, Miller Sch Med, Batchelor Childrens Res Inst, Miami, FL 33136 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 893 BP 725A EP 726A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000892 ER PT J AU Utzschneider, KM Kowdley, KV Yeh, MM Kahn, SE AF Utzschneider, Kristina M. Kowdley, Kris V. Yeh, Matthew M. Kahn, Steven E. TI SITES OF INSULIN RESISTANCE IN OBESE NON-DIABETIC SUBJECTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Utzschneider, Kristina M.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Utzschneider, Kristina M.; Kowdley, Kris V.; Yeh, Matthew M.; Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Kowdley, Kris V.] Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 989 BP 769A EP 769A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000987 ER PT J AU zur Wiesch, JS Lewis-Ximenez, L Reyor, LL Kwok, WW McGovern, BH Lohse, AW Chung, R Allen, TM Kim, AY Lauer, GM AF zur Wiesch, Julian Schulze Lewis-Ximenez, Lia Reyor, Laura L. Kwok, William W. McGovern, Barbara H. Lohse, Ansgar W. Chung, Raymond Allen, Todd M. Kim, Arthur Y. Lauer, Georg M. TI PATTERNS OF HCV CDA plus T CELL IMMUNODOMINANCE IN A LARGE COHORT OF SUBJECTS WITH DIFFERENT STAGES AND OUTCOMES OF HCV INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [zur Wiesch, Julian Schulze; Lohse, Ansgar W.] Univ Klinikum Eppendorf, Med Klin, Hamburg, Germany. [Lewis-Ximenez, Lia] Fiocruz MS, Inst Oswaldo Cruz, Dept Virol, BR-21045900 Rio De Janeiro, Brazil. [Reyor, Laura L.; Chung, Raymond; Allen, Todd M.; Kim, Arthur Y.; Lauer, Georg M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwok, William W.] Benaroya Res Inst, Seattle, WA USA. [McGovern, Barbara H.] Tufts Univ, Lemuel Shattuck Hosp, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1242 BP 880A EP 881A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001239 ER PT J AU Poelstra, K Schuppan, D Popov, Y Millan, JL Malo, MS Hodin, RA AF Poelstra, Klaas Schuppan, Detlef Popov, Yury Millan, Jose L. Malo, Madhu S. Hodin, Richard A. TI GENETIC DELETION OF INTESTINAL ALKALINE PHOSPHATASE ACTIVATES RESIDENT HEPATIC CELLS AND LEADS TO AN INFLUX OF IMMUNE CELLS WITHIN THE LIVER SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Poelstra, Klaas; Schuppan, Detlef; Popov, Yury] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. [Poelstra, Klaas] Univ Groningen, Dept Pharmocokinet Toxicol & Targeting, Groningen, Netherlands. [Malo, Madhu S.; Hodin, Richard A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Millan, Jose L.] Burnham Inst Med Res, La Jolla, CA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1250 BP 884A EP 884A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001247 ER PT J AU Lin, WY Tsai, WL Shao, RX Peng, LF Chung, WJ Sabharwal, S Zhao, H Jang, JY Barlow, L Mendez-Navarro, J Sun, E Chung, R AF Lin, Wenyu Tsai, Wei-Lun Shao, Run-Xuan Peng, Lee F. Chung, Woo Jin Sabharwal, Sabina Zhao, Hong Jang, Jae-Young Barlow, Lydia Mendez-Navarro, Jorge Sun, Eileen Chung, Raymond TI HCV INDUCES TGF-beta 1 EXPRESSION THROUGH GENERATION OF ROS AND NF kappa B ACTIVATION SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Lin, Wenyu; Tsai, Wei-Lun; Shao, Run-Xuan; Peng, Lee F.; Chung, Woo Jin; Sabharwal, Sabina; Zhao, Hong; Jang, Jae-Young; Barlow, Lydia; Mendez-Navarro, Jorge; Sun, Eileen; Chung, Raymond] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1359 BP 931A EP 931A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001355 ER PT J AU Neumann-Haefelin, C Timm, J Schmidt, J Fitzmaurice, K McKiernan, S Kelleher, D Huzly, D Roggendorf, M Allen, TM Blum, HE Thimme, R AF Neumann-Haefelin, Christoph Timm, Joerg Schmidt, Julia Fitzmaurice, Karen McKiernan, Susan Kelleher, Dermot Huzly, Daniela Roggendorf, Michael Allen, Todd M. Blum, Hubert E. Thimme, Robert TI THE PROTECTIVE EFFECT OF HLA-B27 IN HEPATITIS C VIRUS INFECTION REQUIRES PRESENCE OF A GENOTYPE-SPECIFIC IMMUNODOMINANT CD8+T CELL EPITOPE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Schmidt, Julia; Blum, Hubert E.; Thimme, Robert] Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. [Neumann-Haefelin, Christoph] Univ Hosp Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. [Huzly, Daniela] Univ Hosp Freiburg, Dept Virol, Freiburg, Germany. [Timm, Joerg; Roggendorf, Michael] Univ Hosp Essen, Dept Virol, Essen, Germany. [Fitzmaurice, Karen; McKiernan, Susan; Kelleher, Dermot] St James Hosp, Trinity Ctr Hlth Sci, Dublin 8, Ireland. [Neumann-Haefelin, Christoph; Allen, Todd M.] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. RI Neumann-Haefelin, Christoph/E-5550-2011 NR 0 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1370 BP 935A EP 936A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001366 ER PT J AU Chung, WJ Sabharwal, S Tai, AW Lin, W Shoo, RX Jang, JY Tsai, WL Zhao, H Sun, E Peng, LF Chung, R AF Chung, Woo Jin Sabharwal, Sabina Tai, Andrew W. Lin, Wenyu Shoo, Run-Xuan Jang, Jae-Young Tsai, Wei-Lun Zhao, Hong Sun, Eileen Peng, Lee F. Chung, Raymond TI HCV INDUCES INSULIN RESISTANCE BY DECREASING TYROSINE IRS1 PHOSPHORYLATION IN JFH1 INFECTED HEPATOCYTES SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chung, Woo Jin; Sabharwal, Sabina; Tai, Andrew W.; Lin, Wenyu; Shoo, Run-Xuan; Jang, Jae-Young; Tsai, Wei-Lun; Zhao, Hong; Sun, Eileen; Peng, Lee F.; Chung, Raymond] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Woo Jin] Keimyung Univ, Dongsan Med Ctr, Taegu, South Korea. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1375 BP 938A EP 938A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001371 ER PT J AU Jang, JY Shao, RX Lin, WY Chung, WJ Tsai, WL Zhao, H Sabharwal, S Tai, AW Peng, LF Chung, R AF Jang, Jae Young Shao, Run-Xuan Lin, Wenyu Chung, Woo Jin Tsai, Wei-Lun Zhao, Hong Sabharwal, Sabina Tai, Andrew W. Peng, Lee F. Chung, Raymond TI HIV INFECTION INCREASES HCV-INDUCED HEPATOCYTE APOPTOSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Jang, Jae Young; Shao, Run-Xuan; Lin, Wenyu; Chung, Woo Jin; Tsai, Wei-Lun; Zhao, Hong; Sabharwal, Sabina; Tai, Andrew W.; Peng, Lee F.; Chung, Raymond] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1386 BP 942A EP 943A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001382 ER PT J AU Tsai, WL Lin, WY Shao, RX Peng, LF Chung, WJ Jang, JY Sabharwal, S Zhao, H Corey, K Mendez-Navarro, J Sun, E Barlow, L Chung, R AF Tsai, Wei-Lun Lin, Wenyu Shao, Run-Xuan Peng, Lee F. Chung, Woo Jin Jang, Jae-Young Sabharwal, Sabina Zhao, Hong Corey, Kathleen Mendez-Navarro, Jorge Sun, Eileen Barlow, Lydia Chung, Raymond TI HCV ACTIVATES THE UNFOLDED PROTEIN RESPONSE BY INCREASING OXIDATIVE STRESS IN A JNK-, P38 MAPK-, AND MEK-DEPENDENT MANNER SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tsai, Wei-Lun; Lin, Wenyu; Shao, Run-Xuan; Peng, Lee F.; Chung, Woo Jin; Jang, Jae-Young; Sabharwal, Sabina; Zhao, Hong; Corey, Kathleen; Mendez-Navarro, Jorge; Sun, Eileen; Barlow, Lydia; Chung, Raymond] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1398 BP 948A EP 948A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001394 ER PT J AU Li, QS Brass, AL Ng, A Xavier, R Liang, TJ Elledge, SJ AF Li, Qisheng Brass, Abraham L. Ng, Aylwin Xavier, Ramnik Liang, T. Jake Elledge, Stephen J. TI A GENOME-WIDE GENETIC SCREEN FOR HOST FACTORS REQUIRED FOR HEPATITIS C VIRUS PROPAGATION SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Li, Qisheng; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Brass, Abraham L.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Brass, Abraham L.] Harvard Univ, Sch Med, Boston, MA USA. [Brass, Abraham L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Ng, Aylwin; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Div Genet,Brigham & Womens Hosp, Boston, MA 02115 USA. RI Li, Qisheng/K-1909-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1404 BP 950A EP 951A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001400 ER PT J AU Shao, RX Lin, WY Peng, LF Chung, WJ Jang, JY Sabharwal, S Mendez-Navarro, J Tsai, WL Zhao, H Chung, R AF Shao, Run-Xuan Lin, Wenyu Peng, Lee F. Chung, Woo Jin Jang, Jae-Young Sabharwal, Sabina Mendez-Navarro, Jorge Tsai, Wei-Lun Zhao, Hong Chung, Raymond TI HCV AND SOCS3 ARE RECIPROCALLY INHIBITORY IN CELL CULTURE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shao, Run-Xuan; Lin, Wenyu; Peng, Lee F.; Chung, Woo Jin; Jang, Jae-Young; Sabharwal, Sabina; Mendez-Navarro, Jorge; Tsai, Wei-Lun; Zhao, Hong; Chung, Raymond] Massachusetts Gen Hosp, Boston, MA 02114 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1406 BP 951A EP 951A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001402 ER PT J AU Corey, KE Mendez-Navarro, J Patwardhan, V Chung, R AF Corey, Kathleen E. Mendez-Navarro, Jorge Patwardhan, Vilas Chung, Raymond TI ACUTE HEPATITIS C INFECTION IS ASSOCIATED WITH HYPOLIPIDEMIA SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Corey, Kathleen E.; Mendez-Navarro, Jorge; Chung, Raymond] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1432 BP 963A EP 963A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001428 ER PT J AU Kamal, S Ghoraba, D Nabegh, L Nasser, I Motaoe, M Sayed, ME Gohary, I AF Kamal, Sanaa Ghoraba, Dalia Nabegh, Leila Nasser, Imad Motaoe, Mona Sayed, Mohamed E. Gohary, Iman TI PEGYLATED INTERFERON ALFA-2A VS PEGYLATED INTERFERON ALFA-2B, PLUS RIBAVIRIN, FOR CHRONIC HEPATITIS C GENOTYPE 4 PATIENTS: A RANDOMIZED CONTROLLED TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kamal, Sanaa] Tufts Sch Med, Boston, MA USA. [Kamal, Sanaa; Ghoraba, Dalia; Nabegh, Leila; Motaoe, Mona; Sayed, Mohamed E.; Gohary, Iman] Ain Shams Univ, Cairo, Egypt. [Nasser, Imad] BIDMC, Boston, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1566 BP 1025A EP 1026A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001561 ER PT J AU Corey, KE Kane, E Munroe, C Barlow, LL Zheng, H Chung, RT AF Corey, Kathleen E. Kane, Erin Munroe, Craig Barlow, Lydia L. Zheng, Hui Chung, Raymond T. TI Hepatitis C Virus Infection and Its Clearance Alter Circulating Lipids: Implications for Long-Term Follow-Up SO HEPATOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN RECEPTOR; SERUM-CHOLESTEROL; RNA REPLICATION; PROTEIN; MEN; INTERFERON; PREVENTION; TRIAL; RISK AB Hepatitis C associated hypolipidemia has been demonstrated in studies from Europe and Africa. In two linked studies, we evaluated the relationship between hepatitis C infection and treatment with lipid levels in an American cohort and determined the frequency of clinically significant posttreatment hyperlipidemia. First, a case-control analysis of patients with and without hepatitis C was performed. The HCV Group consisted of 179 infected patients. The Uninfected Control Group consisted of 180 age-matched controls. Fasting cholesterol, low density lipoprotein (LDL), high density lipoprotein and triglycerides; were compared. Next was a retrospective cohort study (Treated Hepatitis C Group) of 87 treated hepatitis C patients with lipid data before and after therapy was performed. In the case-control analysis, the HCV Group had significantly lower LDL and cholesterol than the Uninfected Control Group. In the retrospective cohort, patients in the Treated Hepatitis C Group who achieved viral clearance had increased LDL and cholesterol from baseline compared to patients without viral clearance. These results persisted when adjusted for age, sex, and genotype. 13% of patients with viral clearance had increased LDL and 33% experienced increases in cholesterol to levels warranting lipid lowering therapy. Conclusion: Hepatitis C is associated with decreased cholesterol and LDL levels. This hypolipidemia resolves with successful hepatitis C treatment but persists in nonresponders. A significant portion of successfully treated patients experience LDL and cholesterol rebound to levels associated with increased coronary disease risk. Lipids should be carefully monitored in persons receiving antiviral therapy. (HEPATOLOGY 2009;50:1030-1037.) C1 [Corey, Kathleen E.; Barlow, Lydia L.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Corey, Kathleen E.; Kane, Erin; Zheng, Hui; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Munroe, Craig] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIDDK NIH HHS [T32 DK007191] NR 24 TC 71 Z9 73 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 BP 1030 EP 1037 DI 10.1002/hep.23219 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JU UT WOS:000270455800008 PM 19787818 ER PT J AU Davis, GL Alter, MJ El-Serag, HB Poynard, T Jennings, LW AF Davis, Gary L. Alter, Miriam J. El-Serag, Hashem B. Poynard, Thierry Jennings, Linda W. TI AGING OF HEPATITIS C INFECTED PERSONS IN THE UNITED STATES: A MULTIPLE COHORT MODEL OF HCV PREVALENCE AND DISEASE PROGRESSION SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Davis, Gary L.; Jennings, Linda W.] Baylor Univ Hosp Dallas, Div Hepatol Liver Transplant, Dallas, TX USA. [Alter, Miriam J.] Univ Texas Med Branch, Infect Dis Epidemiol Program, Galveston, TX USA. [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [El-Serag, Hashem B.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Poynard, Thierry] Hepato Gastro Grp Hosp, Paris, France. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1613 BP 1050A EP 1051A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001608 ER PT J AU Fontana, RJ Lok, AS Dienstag, JL Naishadham, D Bonkovsky, HL Wright, EC Goodman, ZD Sterling, RK AF Fontana, Robert J. Lok, Anna S. Dienstag, Jules L. Naishadham, Deepa Bonkovsky, Herbert L. Wright, Elizabeth C. Goodman, Zachary D. Sterling, Richard K. TI SERUM FIBROSIS MARKERS ARE ASSOCIATED WITH CLINICAL OUTCOMES AND HISTOLOGICAL PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) AND ADVANCED FIBROSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Fontana, Robert J.; Lok, Anna S.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Bonkovsky, Herbert L.] Carolina Med Ctr, Dept Med, Charlotte, NC USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Dept Pathol, Washington, DC 20306 USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Naishadham, Deepa] New England Res Inst, Boston, MA USA. [Wright, Elizabeth C.] NIH, Liver Dis Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1625 BP 1056A EP 1057A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001620 ER PT J AU Rodriguez-Torres, M Brau, N Rodriguez-Orengo, JF Ortiz-Lasanta, G Segarra-Alonso, O Marxuach, AM AF Rodriguez-Torres, Maribel Brau, Norbert Rodriguez-Orengo, Jose F. Ortiz-Lasanta, Grisell Segarra-Alonso, Omar Marxuach, Acisclo M. TI SEVERITY OF LIVER STEATOSIS AFFECTS PROGRESSION OF DISEASE IN MONOINFECTED PATIENTS BUT NOT IN HCV/HIV CO-INFECTED PATIENTS SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Rodriguez-Torres, Maribel; Rodriguez-Orengo, Jose F.; Ortiz-Lasanta, Grisell; Segarra-Alonso, Omar; Marxuach, Acisclo M.] Fdn Invest Diego, Santurce, PR USA. [Rodriguez-Torres, Maribel] Ponce Sch Med, Ponce, PR USA. [Brau, Norbert] Bronx Vet Affairs Med Ctr, New York, NY USA. [Brau, Norbert] Mt Sinai Sch Med, New York, NY USA. [Rodriguez-Orengo, Jose F.] UPR Sch Med, Dept Biochem, San Juan, PR 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1633 BP 1060A EP 1060A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001628 ER PT J AU Gastaldelli, A Harrison, SA Belfort-Aguilar, R Hardies, LJ Balas, B Schenker, S Cusi, K AF Gastaldelli, Amalia Harrison, Stephen A. Belfort-Aguilar, Renata Hardies, Lou Jean Balas, Bogdan Schenker, Steven Cusi, Kenneth TI Importance of Changes in Adipose Tissue Insulin Resistance to Histological Response During Thiazolidinedione Treatment of Patients with Nonalcoholic Steatohepatitis SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; PLACEBO-CONTROLLED TRIAL; PPAR-GAMMA; NONDIABETIC SUBJECTS; DIABETES-MELLITUS; HEPATIC STEATOSIS; HEALTHY-SUBJECTS; ACID METABOLISM; GENE-EXPRESSION; IN-VIVO AB Pioglitazone treatment improves insulin resistance (IR), glucose metabolism, hepatic steatosis, and necroinflammation in patients with nonalcoholic steatohepatitis (NASH). Because abnormal lipid metabolism/elevated plasma free fatty acids (FFAs) are important to the pathophysiology of NASH, we examined the impact of pioglitazone therapy on adipose tissue insulin resistance (Adipo-IR) during the treatment of patients with NASH. To this end, we assessed glucose/lipid metabolism in 47 patients with impaired glucose tolerance/type 2 diabetes mellitus and NASH and 20 nondiabetic controls. All individuals underwent a 75-g oral glucose tolerance test (OGTT) in which we measured glucose tolerance, IR, and suppression of plasma FFAs. We also measured Adipo-IR index (fasting, FFAs X insulin), hepatic fat by magnetic resonance spectroscopy, and liver histology (liver biopsy). Patients were randomized (double-blind) to diet plus pioglitazone (45 mg/day) or placebo for 6 months, and all measurements were repeated. We found that patients with NASH had severe Adipo-IR and low adiponectin levels. Fasting FFAs were increased and their suppression during the OGTT was impaired. Adipo-IR was strongly associated with hepatic fat (r=0.54) and reduced glucose clearance both fasting (r=0.34) and during the OGTT (r=0.40, all P<0.002). Pioglitazone significantly improved glucose tolerance and glucose clearance, steatosis and necroinflammation (all P<0.01-0.001 versus placebo). Fasting/postprandial plasma FFAs decreased to levels of controls with pioglitazone (P<0.02 versus placebo). Adipo-IR decreased by 47% and correlated with the reduction of hepatic fat (r=0.46, P=0.009) and with the reduction in hepatic necroinflammation (r=0.47, P=0.0007). Conclusion: Patients with NASH have severe Adipo-IR independent of the degree of obesity. Amelioration of Adipo-IR by pioglitazone is closely related to histological improvement and plays an important role during treatment of patients with NASH. (HEPATOLOGY 2009;50:1087-1093.) C1 [Gastaldelli, Amalia] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, Audie L Murphy Vet Adm Med Ctr, San Antonio, TX 78248 USA. [Hardies, Lou Jean] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, Res Imaging Ctr, San Antonio, TX 78248 USA. [Schenker, Steven] Univ Texas Hlth Sci Ctr San Antonio, Div Gastroenterol, San Antonio, TX 78248 USA. [Gastaldelli, Amalia] CNR, Fdn G Monasterio, Pisa, Italy. [Harrison, Stephen A.] Brooke Army Med Ctr, Div Gastroenterol, San Antonio, TX USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, Audie L Murphy Vet Adm Med Ctr, San Antonio, TX 78248 USA. EM cusi@uthscsa.edu RI Hardies, Lou /F-2102-2010; Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU NCATS NIH HHS [UL1 TR000149]; NCRR NIH HHS [UL 1RR025767, UL1 RR025767] NR 50 TC 98 Z9 101 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 BP 1087 EP 1093 DI 10.1002/hep.23116 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JU UT WOS:000270455800015 PM 19670459 ER PT J AU Moro, N Gassler, N Nevzorova, YA Sicinski, P Trautwein, C Liedtke, C AF Moro, Nives Gassler, Nikolaus Nevzorova, Yulia A. Sicinski, Peter Trautwein, Christian Liedtke, Christian TI INACTIVATION OF CYCLIN E1 BUT NOT OF CYCLIN E2 INHIBITS CHEMICALLY INDUCED HEPATOCARCINOGENESIS IN MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Moro, Nives; Nevzorova, Yulia A.; Trautwein, Christian; Liedtke, Christian] Univ Hosp Aachen, Dept Med 3, Aachen, Germany. [Gassler, Nikolaus] Univ Hosp Aachen, Inst Pathol, Aachen, Germany. [Sicinski, Peter] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1804 BP 1137A EP 1137A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001798 ER PT J AU Speliotes, EK Butler, JL Palmer, C Kathiresan, S Voight, BF Sanyal, AJ Hirschhorn, JN AF Speliotes, Elizabeth K. Butler, Johannah L. Palmer, Cameron Kathiresan, Sekar Voight, Benjamin F. Sanyal, Arun J. Hirschhorn, Joel N. CA GIANT Consortium TI PNPLA3 VARIANTS CONFER INCREASED RISK FOR LIVER BUT NOT METABOLIC DISEASE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Speliotes, Elizabeth K.; Voight, Benjamin F.; Hirschhorn, Joel N.] Broad Inst, Populat Genet & Metab Initiat, Cambridge, MA USA. [Butler, Johannah L.; Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Boston, MA 02115 USA. [GIANT Consortium] Genet Invest Anthropometr Traits Consortium, Cambridge, MA USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1884 BP 1172A EP 1173A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001877 ER PT J AU Malandraki, GA Sutton, BP Perlman, AL Karampinos, DC Conway, C AF Malandraki, Georgia A. Sutton, Bradley P. Perlman, Adrienne L. Karampinos, Dimitrios C. Conway, Charles TI Neural Activation of Swallowing and Swallowing-Related Tasks in Healthy Young Adults: An Attempt to Separate the Components of Deglutition SO HUMAN BRAIN MAPPING LA English DT Review DE neuroimaging; swallowing; fMRI; deglutition; neurophysiology ID SUPPLEMENTARY MOTOR AREA; CEREBRAL CORTICAL REPRESENTATION; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY SOMATOSENSORY CORTEX; ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; FUNCTIONAL NEUROANATOMY; TONGUE MOVEMENT; COUGH REFLEX; INTERINDIVIDUAL VARIABILITY AB Understanding the underlying neural pathways that govern the highly complex neuromuscular action of swallowing is considered crucial in the process of correctly identifying and treating swallowing disorders. The aim of the present investigation was to identify the neural activations of the different components of deglutition in healthy young adults using functional magnetic resonance imaging (fMRI). Ten right-handed young healthy individuals were scanned in a 3-Tesla Siemens Allegra MRI scanner. Participants were visually cued for both a "Swallow" task and for component/control tasks ("Prepare to swallow", "Tap Your tongue", and "Clear Your throat") in a randomized order (event-related design). Behavioral interleaved gradient (BIG) methodology was used to address movement-related artifacts. Areas activated during each of the three component tasks enabled a partial differentiation of the neural localization for various components of the swallow. Areas that were more activated during throat clearing than other components included the posterior insula and small portions of the post- and pre-central gyri bilaterally. Tongue tapping showed higher activation in portions of the primary sensorimotor and premotor cortices and the parietal lobules. Planning did not show any areas that were more activated than in the other component tasks. When swallowing was compared with all other tasks, there was significantly more activation in the cerebellum, thalamus, cigulate gyrus, and all areas of the primary sensorimotor cortex bilaterally. Hum Brain Mapp 30:3209-3226, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Malandraki, Georgia A.; Perlman, Adrienne L.] Univ Illinois, Dept Speech & Hearing Sci, Urbana, IL 61801 USA. [Sutton, Bradley P.; Conway, Charles] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Karampinos, Dimitrios C.] Univ Illinois, Dept Mech Engn, Urbana, IL 61801 USA. RP Malandraki, GA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison 2500 Overlook Terrace,GRECC-11G, Madison, WI 53705 USA. EM gmaland@medicine.wisc.edu RI Sutton, Bradley/A-4801-2008; Karampinos, Dimitrios/A-5994-2011 OI Sutton, Bradley/0000-0002-8443-0408; Karampinos, Dimitrios/0000-0003-4922-3662 FU Biomedical Imaging Center of the Beckman Institute at UIUC FX The authors thank the staff and management of the Biomedical Imaging Center of the Beckman Institute at UIUC. NR 102 TC 46 Z9 50 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2009 VL 30 IS 10 BP 3209 EP 3226 DI 10.1002/hbm.20743 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 507LB UT WOS:000270853700011 PM 19247994 ER PT J AU Dirice, E Sanlioglu, AD Kahraman, S Ozturk, S Balci, MK Omer, A Griffith, TS Sanlioglu, S AF Dirice, Ercument Sanlioglu, Ahter Dilsad Kahraman, Sevim Ozturk, Saffet Balci, Mustafa Kemal Omer, Abdulkadir Griffith, Thomas S. Sanlioglu, Salih TI Adenovirus-Mediated TRAIL Gene (Ad5hTRAIL) Delivery into Pancreatic Islets Prolongs Normoglycemia in Streptozotocin-Induced Diabetic Rats SO HUMAN GENE THERAPY LA English DT Article ID TNF-ALPHA; LIGAND EXPRESSION; INDUCED APOPTOSIS; LOCAL EXPRESSION; BETA-CELLS; NOD MICE; NECROSIS; DEATH; RECEPTORS; THERAPY AB Type 1 diabetes (T1D), characterized by permanent destruction of insulin-producing beta cells, is lethal unless conventional exogenous insulin therapy or whole-organ transplantation is employed. Although pancreatic islet transplantation is a safer and less invasive method compared with whole-organ transplant surgery, its treatment efficacy has been limited by islet graft malfunction and graft failure. Thus, ex vivo genetic engineering of beta cells is necessary to prolong islet graft survival. For this reason, a novel gene therapy approach involving adenovirus-mediated TRAIL gene delivery into pancreatic islets was tested to determine whether this approach would defy autoreactive T cell assault in streptozotocin (STZ)-induced diabetic rats. To test this, genetically modified rat pancreatic islets were transplanted under the kidney capsule of STZ-induced diabetic rats, and diabetic status ( blood sugar and body weight) was monitored after islet transplantation. STZ-induced diabetic rats carrying Ad5hTRAIL-infected islets experienced prolonged normoglycemia compared with animals grafted with mock-infected or AdCMVLacZ-infected islets. In addition, severe insulitis was detected in animals transplanted with mock-infected or AdCMVLacZ-infected islets, whereas the severity of insulitis was reduced in animals engrafted with Ad5hTRAIL-infected islets. Thus, TRAIL overexpression in pancreatic islets extends allograft survival and function, leading to a therapeutic benefit in STZ-induced diabetic rats. C1 [Dirice, Ercument; Sanlioglu, Ahter Dilsad; Kahraman, Sevim; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Dept Med Genet, Human Gene Therapy Div, TR-07070 Antalya, Turkey. [Dirice, Ercument; Sanlioglu, Ahter Dilsad; Kahraman, Sevim] Akdeniz Univ, Fac Med, Dept Med Biol & Genet, TR-07070 Antalya, Turkey. [Ozturk, Saffet] Akdeniz Univ, Fac Med, Dept Histol & Embryol, TR-07070 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Balci, Mustafa Kemal] Akdeniz Univ, Fac Med, Dept Med, Div Endocrinol & Metab Dis, TR-07070 Antalya, Turkey. [Griffith, Thomas S.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. RP Sanlioglu, S (reprint author), Akdeniz Univ, Fac Med, Dept Med Genet, Human Gene Therapy Div, B Block,1st Floor Campus, TR-07070 Antalya, Turkey. EM sanlioglu@akdeniz.edu.tr RI Ozturk, Saffet/C-1239-2016; BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Ahter/C-6504-2016; Sanlioglu, Salih/F-9305-2016; Dirice, Ercument/B-2825-2017; OI BALCI, Mustafa Kemal/0000-0002-6494-3249; Sanlioglu, Ahter/0000-0003-4504-0375; Kahraman, Sevim/0000-0002-2880-6589 FU Scientific and Technological Research Council of Turkey [TUBITAK-104S224]; Akdeniz University Scientific Research Project Administration Division [2007.03.0122.003] FX This work is supported by grants from the Scientific and Technological Research Council of Turkey (TUBITAK-104S224) and Akdeniz University Scientific Research Project Administration Division (2007.03.0122.003). The authors thank Fatma Zehra Hapil for technical assistance. NR 50 TC 18 Z9 20 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2009 VL 20 IS 10 BP 1177 EP 1189 DI 10.1089/hum.2009.039 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 509OH UT WOS:000271026800009 PM 19572802 ER PT J AU Sieh, W Choi, Y Chapman, NH Craig, UK Steinbart, EJ Rothstein, JH Oyanagi, K Garruto, RM Bird, TD Galasko, DR Schellenberg, GD Wijsman, EM AF Sieh, Weiva Choi, Yoonha Chapman, Nicola H. Craig, Ulla-Katrina Steinbart, Ellen J. Rothstein, Joseph H. Oyanagi, Kiyomitsu Garruto, Ralph M. Bird, Thomas D. Galasko, Douglas R. Schellenberg, Gerard D. Wijsman, Ellen M. TI Identification of novel susceptibility loci for Guam neurodegenerative disease: challenges of genome scans in genetic isolates SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONISM-DEMENTIA COMPLEX; MULTIPOINT LINKAGE ANALYSIS; MULTILOCUS GENOTYPE DATA; SIB-PAIR METHOD; NEUROFIBRILLARY TANGLES; ISOLATED POPULATIONS; CLINICAL-FEATURES; ALZHEIMER-DISEASE; LOCATION SCORES AB Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a fatal neurodegenerative disease found in the Chamorro people of Guam and other Pacific Island populations. The etiology is unknown, although both genetic and environmental factors appear important. To identify loci for ALS/PDC, we conducted both genome-wide linkage and association analyses, using approximately 400 microsatellite markers, in the largest sample assembled to date, comprising a nearly complete sample of all living and previously sampled deceased cases. A single, large, complex pedigree was ascertained from a village on Guam, with smaller families and a case-control sample ascertained from the rest of Guam by population-based neurological screening and archival review. We found significant evidence for two regions with novel ALS/PDC loci on chromosome 12 and supportive evidence for the involvement of the MAPT region on chromosome 17. D12S1617 on 12p gave the strongest evidence of linkage (maximum LOD score, Z(max) = 4.03) in our initial scan, with additional support in the complete case-control sample in the form of evidence of allelic association at this marker and another nearby marker. D12S79 on 12q also provided significant evidence of linkage (Z(max) = 3.14) with support from flanking markers. Our results suggest that ALS/PDC may be influenced by as many as three loci, while illustrating challenges that are intrinsic in genetic analyses of isolated populations, as well as analytical strategies that are useful in this context. Elucidation of the genetic basis of ALS/PDC should improve our understanding of related neurodegenerative disorders including Alzheimer disease, Parkinson disease, frontotemporal dementia and ALS. C1 [Sieh, Weiva; Chapman, Nicola H.; Rothstein, Joseph H.; Bird, Thomas D.; Wijsman, Ellen M.] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA. [Choi, Yoonha; Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Steinbart, Ellen J.; Bird, Thomas D.; Schellenberg, Gerard D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schellenberg, Gerard D.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Schellenberg, Gerard D.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Wijsman, Ellen M.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Sieh, Weiva] Stanford Univ, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA. [Craig, Ulla-Katrina] Univ Guam, Micronesian Hlth & Aging Study, Mangilao, GU 96923 USA. [Steinbart, Ellen J.; Bird, Thomas D.; Schellenberg, Gerard D.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Oyanagi, Kiyomitsu] Tokyo Metropolitan Inst Neurosci, Dept Neuropathol, Tokyo, Japan. [Garruto, Ralph M.] SUNY Binghamton, Dept Anthropol, Lab Biomed Anthropol & Neurosci, Binghamton, NY 13902 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Wijsman, EM (reprint author), Univ Washington, Div Med Genet, Dept Med, Box 357720, Seattle, WA 98195 USA. EM wijsman@u.washington.edu OI Wijsman, Ellen/0000-0002-2725-6669 FU National Institutes of Health [AG14382, AG11762, AG05136, GM46255]; Department of Veterans Affairs FX This work was funded by the National Institutes of Health (AG14382; AG11762; AG05136; and GM46255) and by the Department of Veterans Affairs. NR 95 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2009 VL 18 IS 19 BP 3725 EP 3738 DI 10.1093/hmg/ddp300 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 505PZ UT WOS:000270707900017 PM 19567404 ER PT J AU Daumerie, G Bridges, L Yancey, S Huang, P Davis, W Loscalzo, J Pointer, MA AF Daumerie, Geraldine Bridges, Lakeesha Yancey, Sadiqa Huang, Paul Davis, Wendell Loscalzo, Joseph Pointer, Mildred A. TI Stress Enhances High Salt-Induced Renal Injury in eNOS Deficiency SO HYPERTENSION LA English DT Meeting Abstract CT 63rd High Blood Pressure Research Conference CY SEP 23-26, 2009 CL Chicago, IL C1 [Daumerie, Geraldine] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bridges, Lakeesha; Yancey, Sadiqa; Pointer, Mildred A.] N Carolina Cent Univ, Durham, NC USA. [Huang, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Davis, Wendell] Biogen Idec Inc, Cambridge, MA USA. [Loscalzo, Joseph] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2009 VL 54 IS 4 BP E75 EP E75 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 494XJ UT WOS:000269852600268 ER PT J AU Hyndman, KA Elmarakby, A Kohan, DE Huang, PL Pollock, DM Pollock, JS AF Hyndman, Kelly A. Elmarakby, Ahmed Kohan, Donald E. Huang, Paul L. Pollock, David M. Pollock, Jennifer S. TI Collecting Duct-Specific Nitric Oxide Synthase-1 Knockout Mice Are Hypertensive SO HYPERTENSION LA English DT Meeting Abstract CT 63rd High Blood Pressure Research Conference CY SEP 23-26, 2009 CL Chicago, IL C1 [Hyndman, Kelly A.; Elmarakby, Ahmed; Pollock, David M.; Pollock, Jennifer S.] Med Coll Georgia, Augusta, GA 30912 USA. [Kohan, Donald E.] Univ Utah, Salt Lake City, UT USA. [Huang, Paul L.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2009 VL 54 IS 4 BP E34 EP E34 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 494XJ UT WOS:000269852600080 ER PT J AU Palomino, Z Bouley, R Jung, FF Casarini, DE AF Palomino, Zaira Bouley, Richard Jung, Flavia F. Casarini, Dulce E. TI Downregulation Effect Of Angiotensin(1-7) On AQP1 Is Mediated By Inhibition Of ACE And Stimulation Of ACE2 SO HYPERTENSION LA English DT Meeting Abstract CT 63rd High Blood Pressure Research Conference CY SEP 23-26, 2009 CL Chicago, IL C1 [Palomino, Zaira; Casarini, Dulce E.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Bouley, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jung, Flavia F.] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2009 VL 54 IS 4 BP E113 EP E113 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 494XJ UT WOS:000269852600453 ER PT J AU Satou, R Miyata, K Gonzales-Villalobos, RA Katsurada, A Acres, OW Urushihara, M Ingelfinger, JR Navar, LG Kobori, H AF Satou, Ryousuke Miyata, Kayoko Gonzales-Villalobos, Romer A. Katsurada, Akemi Acres, Omar W. Urushihara, Maki Ingelfinger, Julie R. Navar, L. G. Kobori, Hiroyuki TI Interferon gamma Biphasically Regulates Angiotensinogen Expression in Renal Proximal Tubular Cells SO HYPERTENSION LA English DT Meeting Abstract CT 63rd High Blood Pressure Research Conference CY SEP 23-26, 2009 CL Chicago, IL C1 [Satou, Ryousuke; Miyata, Kayoko; Gonzales-Villalobos, Romer A.; Katsurada, Akemi; Acres, Omar W.; Urushihara, Maki; Navar, L. G.; Kobori, Hiroyuki] Tulane Univ, New Orleans, LA 70118 USA. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2009 VL 54 IS 4 BP E126 EP E126 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 494XJ UT WOS:000269852600511 ER PT J AU Sun, B Williams, J Conlin, PR Svetkey, LP AF Sun, Bei Williams, Jonathan Conlin, Paul R. Svetkey, Laura P. TI beta 2-Adrenergic Receptor Genotype Affects the Renin-Angiotensin-Aldosterone System Response to the DASH Dietary Pattern SO HYPERTENSION LA English DT Meeting Abstract CT 63rd High Blood Pressure Research Conference CY SEP 23-26, 2009 CL Chicago, IL C1 [Sun, Bei; Williams, Jonathan; Conlin, Paul R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Conlin, Paul R.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Svetkey, Laura P.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2009 VL 54 IS 4 BP E46 EP E46 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 494XJ UT WOS:000269852600134 ER PT J AU Shire, DB Kelly, SK Chen, JH Doyle, P Gingerich, MD Cogan, SF Drohan, WA Mendoza, O Theogarajan, L Wyatt, JL Rizzo, JF AF Shire, Douglas B. Kelly, Shawn K. Chen, Jinghua Doyle, Patrick Gingerich, Marcus D. Cogan, Stuart F. Drohan, William A. Mendoza, Oscar Theogarajan, Luke Wyatt, John L. Rizzo, Joseph F. TI Development and Implantation of a Minimally Invasive Wireless Subretinal Neurostimulator SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Electrode array; neural prosthesis; retinal implant; retinal prosthesis; subretinal; stimulation ID ELECTRICAL-STIMULATION; VISUAL PROSTHESIS; RETINAL PROSTHESIS; PERCEPTUAL THRESHOLDS; MICROELECTRODE ARRAY; VISION PROSTHESIS; UNITED-STATES; DEGENERATION; ELECTRODES; RESPONSES AB A wirelessly operated, minimally invasive retinal prosthesis was developed for preclinical chronic implantation studies in Yucatan minipig models. The implant conforms to the outer wall of the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially designed ab externo surgical technique that fixes the bulk of the prosthesis to the outer surface of the sclera. The implanted device is fabricated on a host polyimide flexible circuit. It consists of a 15-channel stimulator chip, secondary power and data receiving coils, and discrete power supply components. The completed device is encapsulated in poly(dimethylsiloxane) except for the reference/counter electrode and the thin electrode array. In vitro testing was performed to verify the performance of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation patterns as well as pulse strength, duration, and frequency were programmed wirelessly using custom software and a graphical user interface. Wireless operation of the retinal implant has been verified both in vitro and in vivo in three pigs for more than seven months, the latter by measuring stimulus artifacts on the eye surface using contact lens electrodes. C1 [Shire, Douglas B.; Kelly, Shawn K.; Drohan, William A.] VA Boston Healthcare Syst, Vet Affairs Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Shire, Douglas B.; Gingerich, Marcus D.] Cornell Univ, Ithaca, NY 14853 USA. [Rizzo, Joseph F.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Doyle, Patrick] Boston Vet Affairs Res Inst, Boston, MA 02130 USA. [Cogan, Stuart F.] EIC Labs Inc, Norwood, MA 02062 USA. [Mendoza, Oscar; Theogarajan, Luke; Wyatt, John L.] MIT, Cambridge, MA 02139 USA. [Rizzo, Joseph F.] Vet Affairs Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. RP Shire, DB (reprint author), VA Boston Healthcare Syst, Vet Affairs Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. EM dbs6@cornell.edu; skkelly@mit.edu; jinghua_chen@meei.harvard.edu; wpd@mit.edu; mdg37@cornell.edu; scogan@eiclabs.com; billd@mit.edu; dmendoza@mit.edu; ltheogar@ece.uscb.edu; jlw@mit.edu; joseph_rizzo@meei.harvard.edu OI Kelly, Shawn/0000-0003-3533-5268 FU National Science Foundation (NSF) [IIS-0515134]; National Institutes of Health [EY016674-01]; Cornell NanoScale Science and Technology Facility FX This work was supported in part by the Veterans Affairs Center for Innovative Visual Rehabilitation, in part by the National Science Foundation (NSF) (IIS-0515134), in part by the National Institutes of Health (EY016674-01), in part by the NSF's support to the Cornell NanoScale Science and Technology Facility (part of the NationalNanofabrication Infrastructure Network), and in part by private donors. Asterisk indicates corresponding author. NR 53 TC 71 Z9 73 U1 1 U2 15 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 2009 VL 56 IS 10 BP 2502 EP 2511 DI 10.1109/TBME.2009.2021401 PG 10 WC Engineering, Biomedical SC Engineering GA 494SW UT WOS:000269838000018 PM 19403357 ER PT J AU Mok, GSP Wang, YC Tsui, BMW AF Mok, Greta S. P. Wang, Yuchuan Tsui, Benjamin M. W. TI Quantification of the Multiplexing Effects in Multi-Pinhole Small Animal SPECT: A Simulation Study SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE Multi-pinhole collimator; multiplexing; small animal imaging; SPECT ID HIGH-RESOLUTION; RECONSTRUCTION; COLLIMATION; DESIGN; SYSTEM AB Our goal is to study the trade-off between image degradation and improved detection efficiency and resolution from allowing multiplexing in multi-pinhole (MPH) SPECT, and to determine The optimal pinhole number for; MPH design. We used an analytical 3D MPH projector and two digitized phantoms: the mouse whole body (MOBY) phantom and a hot sphere phantom to generate noise-free and noisy projections, simulating pinhole collimators fitted with pre-studied pinhole patterns. We performed three schemes to achieve different degrees of multiplexing: 1. Fixed magnification and detection efficiency; 2. Fixed detection efficiency and changed magnification; 3. Fixed magnification and changed detection efficiency. We generated various noisy data sets by simulating Poisson noise using differently scaled noise-free projections and obtained 20 noise realizations for each setting. All datasets; were reconstructed using 3D MPH ML-EM reconstruction method. We analyzed the quantitative accuracy by the normalized-mean-square-error. We evaluated the image contrast for the hot sphere phantom simulation, and also the image noise by the average normalized-standard-deviation of certain pixels for different degrees of multiplexing. Generally no apparent artifacts were observed in the reconstructed images, illustrating the effectiveness of reconstructions. Bias increased for increased degree of multiplexing. Contrast was not significantly affected by multiplexing in the specific simulation scheme (1). Scheme (2) showed that excessive multiplexing to improve image resolution would not improve the overall trade-off of bias and noise compared to no multiplexing. However, scheme (3) showed that when comparing to no multiplexing, the trade-off improved initially with increased multiplexing by allowing more number of pinholes to improve detection efficiency. The trade-off reached a maximum and decreased with further multiplexing due to image degradation from increased bias. The optimal pinhole number was 7 for a compact camera with size of 12 cm x 12 cm and 9 for a standard. gamma camera with size of 40 cm x 40 cm in this scheme. We conclude that the gains in improved detection efficiency and resolution by increased multiplexing are offset by increased image degradations. All the aforementioned factors must be considered in the optimum MPH collimator design for small animal SPECT imaging. C1 [Mok, Greta S. P.] Chinese Univ Hong Kong, Dept Diagnost Radiol & Organ Imaging, Hong Kong, Hong Kong, Peoples R China. [Wang, Yuchuan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tsui, Benjamin M. W.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA. RP Mok, GSP (reprint author), Chinese Univ Hong Kong, Dept Diagnost Radiol & Organ Imaging, Hong Kong, Hong Kong, Peoples R China. EM gre-tamok@cuhk.edu.hk OI Wang, Yuchuan/0000-0001-5111-6562 FU NIH [EB001558] FX This work was supported by the NIH research grant EB001558 NR 16 TC 30 Z9 31 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD OCT PY 2009 VL 56 IS 5 BP 2636 EP 2643 DI 10.1109/TNS.2009.2023444 PG 8 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 510OW UT WOS:000271100400012 PM 21643442 ER PT J AU Stern, JNH Keskin, DB Romero, V Zuniga, J Encinales, L Li, CL Awad, C Yunis, EJ AF Stern, Joel N. H. Keskin, Derin B. Romero, Viviana Zuniga, Joaquin Encinales, Liliana Li, Changlin Awad, Carlos Yunis, Edmond J. TI Molecular signatures distinguishing active from latent tuberculosis in peripheral blood mononuclear cells, after in vitro antigenic stimulation with purified protein derivative of tuberculin (PPD) or Candida: a preliminary report SO IMMUNOLOGIC RESEARCH LA English DT Article DE Latent tuberculosis (LTBI); Active tuberculosis (ATBI); IL-17; Cytokines; Chemokines ID NITRIC-OXIDE SYNTHASE; BOVIS INFECTED CATTLE; AMINO-ACID COPOLYMERS; TUMOR-NECROSIS-FACTOR; DELTA T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; INTERFERON-GAMMA; IFN-GAMMA; SERUM CONCENTRATIONS AB Purified protein derivative (PPD) or tuberculin skin testing is used to identify infected individuals with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immunity to Mtb. In the present study, we compared PBMC cultures in the presence of tuberculin or Candida antigens using cytokine bead arrays and RNA microarrays. Measurements of different cytokines and chemokines in supernatants of PMBC cultures in the presence of PPD showed increased levels of interferon (IFN)-gamma in active tuberculosis infection (ATBI) and latent TB infected (LTBI) compared to controls, and increased levels of TNF-alpha in ATBI compared with LTBI. Also, we found increase of IL-6 in cultures of PPD positive and controls but not in the cultures with Candida. We also report the molecular signature of tuberculosis infection, in ATBI patients, the following genes were found to be up-regulated and absent in LTBI individuals: two kinases (JAK3 and p38MAPK), four interleukins (IL-7, IL-2, IL-6, and IFN beta 1), a chemokine (HCC-4) a chemokine receptor (CxCR5), two interleukin receptors (IL-1R2 and IL-18R1), and three additional ones (TRAF5, Smad2, CIITA, and NOS2A). By contrast, IL-17 and IGFBP3 were significantly up-regulated in LTBI. And, STAT4, GATA3, Fra-1, and ICOS were down-regulated in ATBI but absent in LTBI. Conversely, TLR-10, IL-15, DORA, and IKK-beta were down-regulated in LTBI but not in ATBI. Interestingly, the majority of the up-regulated genes found in ATBI were found in cultures stimulated with tuberculin (PPD) or Candida antigens, suggesting that these pathogens stimulate similar immunological pathways. We believe that the molecular signature distinguishing active from latent tuberculosis infection may require using cytokine bead arrays along with RNA microarrays testing cell cultures at different times following in vitro proliferation assays using several bacterial antigens and PPD. C1 [Stern, Joel N. H.; Keskin, Derin B.; Romero, Viviana; Encinales, Liliana; Li, Changlin; Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Zuniga, Joaquin] Inst Nacl Enfermedades Resp, Lab Immunobiol & Genet, Mexico City, DF, Mexico. [Awad, Carlos] Hop Santa Clara, Bogota, Colombia. RP Stern, JNH (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM jstern@fas.harvard.edu; edmond_yunis@dfci.harvard.edu OI Stern, Joel N.H./0000-0002-1259-2256 FU Stern Investigative Services (SIS Inc.); Public Health Service (PHS) [HL29583]; National Heart, Lung, and Blood Institute of the National Institute of Health (NIH) [HL59838]; Department of Cancer Immunology and AIDs of the Dana Farber Cancer Institut FX J.N.H.S. was partially supported by Stern Investigative Services (SIS Inc.). E.J.Y. was supported by the Public Health Service (PHS) grants HL29583 and from the National Heart, Lung, and Blood Institute of the National Institute of Health (NIH) HL59838 and fuds form the Department of Cancer Immunology and AIDs of the Dana Farber Cancer Institute. NR 46 TC 26 Z9 27 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X EI 1559-0755 J9 IMMUNOL RES JI Immunol. Res. PD OCT PY 2009 VL 45 IS 1 BP 1 EP 12 DI 10.1007/s12026-008-8024-2 PG 12 WC Immunology SC Immunology GA 495OV UT WOS:000269904000001 PM 18648750 ER PT J AU Ngamskulrungroj, P Himmelreich, U Breger, JA Wilson, C Chayakulkeeree, M Krockenberger, MB Malik, R Daniel, HM Toffaletti, D Djordjevic, JT Mylonakis, E Meyer, W Perfect, JR AF Ngamskulrungroj, Popchai Himmelreich, Uwe Breger, Julia A. Wilson, Christabel Chayakulkeeree, Methee Krockenberger, Mark B. Malik, Richard Daniel, Heide-Marie Toffaletti, Dena Djordjevic, Julianne T. Mylonakis, Eleftherios Meyer, Wieland Perfect, John R. TI The Trehalose Synthesis Pathway Is an Integral Part of the Virulence Composite for Cryptococcus gattii SO INFECTION AND IMMUNITY LA English DT Article ID NEOFORMANS VAR. GATTII; CELL-WALL INTEGRITY; SACCHAROMYCES-CEREVISIAE; TREHALOSE-6-PHOSPHATE PHOSPHATASE; DECREASES INFECTIVITY; CANDIDA-ALBICANS; VANCOUVER-ISLAND; DISTINCT ROLES; GENE; DISRUPTION AB The trehalose pathway is essential for stress tolerance and virulence in fungi. We investigated the importance of this pathway for virulence of the pathogenic yeast Cryptococcus gattii using the highly virulent Vancouver Island, Canada, outbreak strain R265. Three genes putatively involved in trehalose biosynthesis, TPS1 (trehalose-6-phosphate [T6P] synthase) and TPS2 (T6P phosphatase), and degradation, NTH1 (neutral trehalose), were deleted in this strain, creating the R265tps1 Delta, R265tps2 Delta, and R265nth1 Delta mutants. As in Cryptococcus neoformans, cellular trehalose was reduced in the R265tps1 Delta and R265tps2 Delta mutants, which could not grow and died, respectively, at 37 C on yeast extract-peptone-dextrose agar, suggesting that T6P accumulation in R265tps2 Delta is directly toxic. Characterizations of the cryptococcal hexokinases and trehalose mutants support their linkage to the control of glycolysis in this species. However, unlike C. neoformans, the C. gattii R265tps1 Delta mutant demonstrated, in addition, defects in melanin and capsule production, supporting an influence of T6P on these virulence pathways. Attenuated virulence of the R265tps1 Delta mutant was not due solely to its 37 C growth defect, as shown in worm studies and confirmed by suppressor mutants. Furthermore, an intact trehalose pathway controls protein secretion, mating, and cell wall integrity in C. gattii. Thus, the trehalose synthesis pathway plays a central role in the virulence composites of C. gattii through multiple mechanisms. Deletion of NTH1 had no effect on virulence, but inactivation of the synthesis genes, TPS1 and TPS2, has profound effects on survival of C. gattii in the invertebrate and mammalian hosts. These results highlight the central importance of this pathway in the virulence composites of both pathogenic cryptococcal species. C1 [Ngamskulrungroj, Popchai; Chayakulkeeree, Methee; Toffaletti, Dena; Perfect, John R.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Ngamskulrungroj, Popchai; Meyer, Wieland] Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, Mol Mycol Res Lab,Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Ngamskulrungroj, Popchai; Chayakulkeeree, Methee] Mahidol Univ, Siriraj Hosp, Fac Med, Bangkok 10700, Thailand. [Himmelreich, Uwe] Katholieke Univ Leuven, Fac Med, Biomed NMR Unit MoSAIC, Louvain, Belgium. [Breger, Julia A.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilson, Christabel; Chayakulkeeree, Methee; Djordjevic, Julianne T.] Westmead Hosp, Westmead Millennium Inst, Ctr Infect Dis & Microbiol, Fungal Pathogenesis Res Grp, Westmead, NSW 2145, Australia. [Krockenberger, Mark B.; Malik, Richard] Univ Sydney, Fac Vet Sci, Camperdown, NSW, Australia. [Daniel, Heide-Marie] Catholic Univ Louvain, B-1348 Louvain, Belgium. RP Perfect, JR (reprint author), Duke Univ, Med Ctr, Dept Med, Box 102359, Durham, NC 27710 USA. EM perfe001@mc.duke.edu RI Daniel, Heide-Marie/B-3161-2010; Krockenberger, Mark/B-1683-2012; Meyer, Wieland/G-1204-2015 OI Meyer, Wieland/0000-0001-9933-8340 FU Public Service [AI28388, AI73896] FX We thank the following members of the Duke University Mycological Research Unit: Joseph Heitman, James Fraser, Gary Cox, Tom Rude, and Alexander Idnurm, and thank the members of Andrew Alspaugh's laboratory for their scientific advice.; This work was supported by Public Service Grants AI28388 and AI73896. NR 57 TC 45 Z9 47 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2009 VL 77 IS 10 BP 4584 EP 4596 DI 10.1128/IAI.00565-09 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 496ER UT WOS:000269952800045 PM 19651856 ER PT J AU Corey, KE Servoss, JC Casson, DR Kim, AY Robbins, GK Franzini, J Twitchell, K Loomis, SC Abraczinskas, DR Terella, AM Dienstag, JL Chung, RT AF Corey, Kathleen E. Servoss, Julie C. Casson, Deborah R. Kim, Arthur Y. Robbins, Gregory K. Franzini, Jean Twitchell, Katherine Loomis, Susan C. Abraczinskas, Diane R. Terella, Adam M. Dienstag, Jules L. Chung, Raymond T. TI Pilot Study of Postexposure Prophylaxis for Hepatitis C Virus in Healthcare Workers SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID MEDICAL PERSONNEL; VIRAL CLEARANCE; INFECTION; TRANSMISSION; INTERFERON; RISK; EXPOSURE; HCV AB BACKGROUND AND OBJECTIVE. Hepatitis C virus (HCV) transmission occurs in 0.2%-10% of people after accidental needlestick exposures. However, postexposure prophylaxis is not currently recommended. We sought to determine the safety, tolerability, and acceptance of postexposure prophylaxis with peginterferon alfa-2b in healthcare workers (HCWs) exposed to blood from HCV-infected patients. DESIGN. Open-label pilot trial of peginterferon alfa-2b for HCV postexposure prophylaxis. SETTING. Two academic tertiary-referral centers. METHODS. HCWs exposed to blood from HCV-infected patients were informed of the availability of postexposure prophylaxis. Persons who elected postexposure prophylaxis were given weekly doses of peginterferon alfa-2b for 4 weeks. RESULTS. Among 2,702 HCWs identified with potential exposures to bloodborne pathogens, 213 (7.9%) were exposed to an HCV antibody-positive source. Of 51 HCWs who enrolled in the study, 44 (86%) elected to undergo postexposure prophylaxis (treated group). Seven subjects elected not to undergo postexposure prophylaxis (untreated group). No cases of HCV transmission were observed in either the treated or untreated group, and no cases occurred in the remaining 162 HCWs who did not enroll in this study. No serious adverse events related to a peginterferon alfa-2b regimen were recorded, but minor adverse events were frequent. CONCLUSION. In this pilot study, there was a lower than expected frequency of HCV transmission after accidental occupational exposure. Although peginterferon alfa-2b was safe, because of the lack of HCV transmission in either the treated or untreated groups there is little evidence to support routine postexposure prophylaxis against HCV in HCWs. C1 [Corey, Kathleen E.; Servoss, Julie C.; Casson, Deborah R.; Abraczinskas, Diane R.; Terella, Adam M.; Dienstag, Jules L.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kim, Arthur Y.; Robbins, Gregory K.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Loomis, Susan C.] Massachusetts Gen Hosp, Occupat Hlth Serv, Boston, MA 02114 USA. [Franzini, Jean; Twitchell, Katherine] Brigham & Womens Hosp, Occupat Hlth Serv, Boston, MA 02115 USA. [Corey, Kathleen E.; Servoss, Julie C.; Casson, Deborah R.; Kim, Arthur Y.; Robbins, Gregory K.; Abraczinskas, Diane R.; Terella, Adam M.; Dienstag, Jules L.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org RI Robbins, Gregory/F-7988-2011 FU Schering-Plough; Roche Laboratories; Bristol-Myers Squibb; AASLD/Schering Advanced Hepatology Fellowship Program; Vertex FX Schering-Plough provided partial support, as well as peginterferon alfa-2b, for this trial. R. T. C. reports that he has received grant support from Schering-Plough and from Roche Laboratories. K. E. C. reports that she has received funding from Bristol-Myers Squibb. J. C. S. reports that she has received funding from Bristol-Myers Squibb and from the AASLD/Schering Advanced Hepatology Fellowship Program. J.L.D. reports that he has received research support from Vertex, has served as an ad hoc consultant for Achillion Pharmaceuticals, and is on the scientific advisory board for Metabasis Therapeutics, the clinical advisory board for Nucleonics, the adjudication committee for Schering-Plough Research Institute, the safety monitoring board for Human Genome Sciences, and the ad hoc hepatitis advisory board for Abbott Molecular and Boehringer-Ingelheim. All remaining authors report no conflicts of interest relevant to this article. NR 23 TC 7 Z9 7 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2009 VL 30 IS 10 BP 1000 EP 1005 DI 10.1086/605718 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 492YM UT WOS:000269698800011 PM 19743901 ER PT J AU Essers, JB Lee, JJ Kugathasan, S Stevens, CR Grand, RJ Daly, MJ AF Essers, Jonah B. Lee, Jessica J. Kugathasan, Subra Stevens, Christine R. Grand, Richard J. Daly, Mark J. CA NIDDK IBD Genetics Consortium TI Established Genetic Risk Factors Do Not Distinguish Early and Later Onset Crohn's Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease/*genetics; genetic predisposition to disease; polymorphism; single nucleotide; age of onset; child ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; PEDIATRIC-ONSET; SUSCEPTIBILITY LOCI; HUNTINGTON-DISEASE; ULCERATIVE-COLITIS; AGE; CHILDHOOD; MUTATIONS; PHENOTYPE AB Background: Early-onset disease is frequently examined in genetic studies because it is presumed to contain a more severe subset of patients under a higher influence of genetic effects. In light of the dramatic Success of Crohn's disease (CD) gene discovery efforts, we aimed to characterize the contribution of established common risk variants to pediatric CD. Methods: Using 35 confirmed CD risk alleles, we genotyped 384 parent-child trios (mean age of onset 11.7 years) along with 321 healthy controls. We performed association tests on the independent pediatric cohort and compared results to those previously published.(1) We also computed a weighted CD genetic risk score for each affected person. Six variants not previously validated in children (at 5q33, 1q24, 7p12, 12q12, 8q24, and 1q32) were significantly associated with pediatric CD (P < 0.03). Results: We detected no significant association between risk score and age at onset through age 30. This analysis illustrates that the genetic effect of established CD risk variants is similar in early and later onset CD. Conclusions: These results motivate joint analyses of genome-wide association data in early and late onset cohorts and suggest that, rather than established risk variants, independent variants or environmental exposures should be sought as modulators of age of onset. C1 [Essers, Jonah B.; Lee, Jessica J.; Grand, Richard J.] Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Essers, Jonah B.; Daly, Mark J.] Broad Inst, Cambridge, MA USA. [Essers, Jonah B.; Stevens, Christine R.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kugathasan, Subra] Emory Univ, Sch Med, Atlanta, GA USA. EM jonah.essers@childrens.harvard.edu RI Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 FU NIDDK NIH HHS [P30 DK034854, T32 DK007477, T32 DK007477-25, U01 DK062420] NR 35 TC 23 Z9 23 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2009 VL 15 IS 10 BP 1508 EP 1514 DI 10.1002/ibd.20922 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 503YZ UT WOS:000270580000012 PM 19322901 ER PT J AU Bordeianou, L AF Bordeianou, Liliana TI In Flux on Infliximab: Conflicting Studies on Surgical Outcomes SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID ULCERATIVE-COLITIS; POSTOPERATIVE COMPLICATIONS C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2009 VL 15 IS 10 BP 1605 EP 1606 DI 10.1002/ibd.20891 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 503YZ UT WOS:000270580000023 PM 19177548 ER PT J AU Richard, JCM Kacmarek, RM AF Richard, Jean Christophe Marie Kacmarek, Robert M. TI ICU mechanical ventilators, technological advances vs. user friendliness: the right picture is worth a thousand numbers SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID PRESSURE SUPPORT VENTILATION; SIMULATOR; DISPLAY C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richard, Jean Christophe Marie] Rouen Univ Hosp, Med Intens Care Unit, UPRES EA 3830, Paris, France. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 13 TC 5 Z9 6 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2009 VL 35 IS 10 BP 1662 EP 1663 DI 10.1007/s00134-009-1581-6 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 498VD UT WOS:000270171900003 PM 19639301 ER PT J AU Fritsche, CS Simsch, O Weinberg, EJ Orrick, B Stamm, C Kaazempur-Mofrad, MR Borenstein, JT Hetzer, R Vacanti, JP AF Fritsche, Clemens S. Simsch, Oliver Weinberg, Eli J. Orrick, Brian Stamm, Christof Kaazempur-Mofrad, Mohammad R. Borenstein, Jeffrey T. Hetzer, Roland Vacanti, Joseph P. TI Pulmonary tissue engineering using dual-compartment polymer scaffolds with integrated vascular tree SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article DE Tissue engineering; Lung; Microvascular network; MEMS; Alveolocapillary membrane ID EMBRYONIC STEM-CELLS; EPITHELIAL-CELLS; LUNG-TRANSPLANTATION; MICROFABRICATION; TECHNOLOGIES; CONSTRUCTS; CHANNELS; CULTURE; PROTEIN; LIVER AB Objectives: The persistent shortage of donor organs for lung transplantation illustrates the need for new strategies in organ replacement therapy. Pulmonary tissue engineering aims at developing viable hybrid tissue for patients with chronic respiratory failure. Methods: Dual-chamber polymer constructs that mimic the characteristics of the pulmonary air-blood interface were fabricated by microfabrication techniques using the biocompatible polymer polydimethylsiloxane. One compartment ("vascular chamber") was designed as a capillary network to mimic the pulmonary microvasculature. The other compartment ("parenchymal chamber") was designed to permit gas exchange. Immortalized mouse lung epithelium cells (MLE-12) were cultured on the surface of polystyrene microcarrier beads. These beads were subsequently injected into the parenchymal chamber of the dual-chamber microsystems. The vascular compartment was perfused with cell culture medium in a bioreactor and the construct was maintained in culture for 1 week. Results: The microcarriers evenly distributed MLE-12 cells on the parenchymal compartment surface. Confluent cell layers were confirmed by fluorescent and electron microscopy. Adequate proliferation of MLE-12 cells within the construct was monitored via the DNA content. Viability of the cells was maintained over 1 week. Finally, cellular specificity and functional capacity in situ were demonstrated by immunostaining for proSP-B and proSP-C (alveolar epithelium), and by using MLE-12 cells transfected to overexpress green fluorescent protein. Conclusion: We conclude that functional hybrid microsystems mimicking the basic building plan of alveolar tissue can be engineered in vitro. (Int J Artif Organs 2009; 32: 701-10) C1 [Fritsche, Clemens S.; Simsch, Oliver; Stamm, Christof; Hetzer, Roland] Deutsch Herzzentrum Berlin, Lab Tissue Engn, D-13353 Berlin, Germany. [Fritsche, Clemens S.; Simsch, Oliver; Vacanti, Joseph P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tissue Engn & Organ Fabricat Lab,Dept Surg, Boston, MA USA. [Weinberg, Eli J.; Kaazempur-Mofrad, Mohammad R.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Orrick, Brian; Borenstein, Jeffrey T.] Charles Stark Draper Lab Inc, Cambridge, MA USA. RP Fritsche, CS (reprint author), Deutsch Herzzentrum Berlin, Lab Tissue Engn, Augustenburger Pl 1, D-13353 Berlin, Germany. EM clemens_fritsche@web.de RI Stamm, Christof/J-5719-2014 FU Center for Integration of Medicine and Innovative Technology (US Army) [DAMD17-02-2-0006] FX Support from the Center for Integration of Medicine and Innovative Technology (US Army DAMD17-02-2-0006) is gratefully appreciated. NR 29 TC 10 Z9 11 U1 0 U2 7 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD OCT PY 2009 VL 32 IS 10 BP 701 EP 710 PG 10 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 548UW UT WOS:000273994700001 PM 19943231 ER PT J AU Kotsopoulos, J Tworoger, SS DeVivo, I Hankinson, SE Hunter, DJ Willett, WC Chen, WY AF Kotsopoulos, Joanne Tworoger, Shelley S. DeVivo, Immaculata Hankinson, Susan E. Hunter, David J. Willett, Walter C. Chen, Wendy Y. TI +331G/A variant in the progesterone receptor gene, postmenopausal hormone use and risk of breast cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; progesterone receptor; postmenopausal hormones ID ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; B-ISOFORM; FUNCTIONAL POLYMORPHISM; REPRODUCTIVE FUNCTIONS; MAMMOGRAPHIC DENSITY; OVARIAN-CANCER; MAMMARY-GLAND; NURSES HEALTH; MICE LACKING AB A functional promoter polymorphism in the progesterone receptor (PR) gene previously has been associated with an increased risk of postmenopausal breast cancer. Whether the relationship between genetic variation in PR and risk of breast cancer is modified by postmenopausal hormone (PMH) use is unknown. Thus, we conducted a case-control study nested within the prospective Nurses' Health Study to evaluate if the risk of breast cancer associated with having the +331 A risk allele was modified by PMH use. Genotyping of this SNP was available for 1,664 postmenopausal breast cancer cases and 2,391 controls. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer. Women who were carriers of 1 or both variant A alleles had a 31% increased risk of developing breast cancer (95% CI 1.04-1.65). PMH use significantly modified the association between the +331G/A polymorphism and risk (p-interaction <0.05). Among never users of PMH, women who were variant carriers had a significantly increased risk of breast cancer compared to those with the wild-type genotype (OR = 2.57; 95% CI 1.64-4.02). The +331G/A polymorphism was not associated with breast cancer risk among past (OR = 1.23; 95% CI 0.77-1.97) or current (OR = 1.14; 95% CI 0.84-1.56) PMH users. The data from this large prospective study provide evidence for a 2-fold increased risk of developing postmenopausal breast cancer among never users of PMH with the +331G/A SNP. This finding adds to the evidence that the PR has an important etiologic role in breast cancer and should be evaluated in future studies. (C) 2009 UICC C1 [Kotsopoulos, Joanne; Tworoger, Shelley S.; DeVivo, Immaculata; Hankinson, Susan E.; Hunter, David J.; Willett, Walter C.; Chen, Wendy Y.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Kotsopoulos, Joanne; Tworoger, Shelley S.; DeVivo, Immaculata; Hankinson, Susan E.; Hunter, David J.; Willett, Walter C.; Chen, Wendy Y.] Harvard Univ, Sch Med, Boston, MA USA. [Tworoger, Shelley S.; DeVivo, Immaculata; Hankinson, Susan E.; Hunter, David J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kotsopoulos, J (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM nhjok@channing.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046 FU Canadian Cancer Society supported through an award from the National Cancer Institute of Canada FX The authors thank Dr. Rulla Tamimi for her help with the mammographic density portion of the manuscript, Dr. Aditi Hazra for her help with the interpretation of the genetics data as well its, the,study participants of the Nurses' Health Study for their dedication to this study and their contribution to this research. J.K. is a Research Fellow of the Canadian Cancer Society supported through an award from the National Cancer Institute of Canada. NR 50 TC 8 Z9 8 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 1 PY 2009 VL 125 IS 7 BP 1685 EP 1691 DI 10.1002/ijc.24477 PG 7 WC Oncology SC Oncology GA 491GB UT WOS:000269565400023 PM 19462450 ER PT J AU Lu, XM Hamrahi, VF Tompkins, RG Fischman, AJ AF Lu, Xiao-Ming Hamrahi, Victoria F. Tompkins, Ronald G. Fischman, Alan J. TI Effect of insulin levels on the phosphorylation of specific amino acid residues in IRS-1: Implications for burn-induced insulin resistance SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE insulin receptor substrate-1; phosphorylation; degradation; kinase; MS/MS; SILAC ID TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; CAPLC-Q-TOFMICRO; SERINE PHOSPHORYLATION; SKELETAL-MUSCLE; TYROSINE PHOSPHORYLATION; THERMAL-INJURY; SERINE/THREONINE PHOSPHORYLATION AB Alterations in the phosphorylation and/or degradation of insulin receptor substrate-1 (IRS-1) produced by burn injury may be responsible, at least in part, for burn-induced insulin resistance. In particular, following burn injury, reductions in glucose uptake by skeletal muscle may be secondary to altered abundance and/or phosphorylation of IRS-1. In this study, we performed in vitro experiments with 293 cells transfected with IRS-1. These studies demonstrated that there is a dramatic change in the phosphorylation pattern of Tyr, Ser and Thr residues in IRS-1 as a function of insulin levels. Specifically, Ser and Thr residues in the C-terminal region were phosphorylated only at high insulin levels. SILAC (stable isotope labeling with amino acids in cell culture) followed by sequencing of C-terminal IRS-1 fragments by tandem mass spectrometry demonstrated that there is significant protein cleavage at these sites. These findings suggest that one of the biological roles of the C-terminal region of IRS-1 may be negative modulation of the finely coordinated insulin signaling system. Clearly, this could represent an important factor in insulin resistance, and identification of kinase inhibitors that are responsible for the phosphorylation may foster new lines of research for the development of drugs for treating insulin resistance. C1 [Fischman, Alan J.] Shriners Hosp Children, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fischman, AJ (reprint author), Shriners Hosp Children, Massachusetts Gen Hosp, Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM aajjff@gmail.com FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-14] NR 86 TC 4 Z9 4 U1 0 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD OCT PY 2009 VL 24 IS 4 BP 531 EP 538 DI 10.3892/ijmm_00000262 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 496AW UT WOS:000269941300016 PM 19724894 ER PT J AU Benoit, MM Silvera, VM Nichollas, R Jones, D McGill, T Rahbar, R AF Benoit, Margo McKenna Silvera, V. Michelle Nichollas, Richard Jones, Dwight McGill, Trevor Rahbar, Reza TI Image guidance systems for minimally invasive sinus and skull base surgery in children SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article; Proceedings Paper CT Eastern Section Meeting of the Triological-Society CY JAN 24-25, 2009 CL Boston, MA SP Triol Soc DE Image-guided surgery; Paranasal sinus; Skull base; Endoscopic surgery; Minimally invasive surgery ID COMPUTER-ASSISTED NAVIGATION; MANAGEMENT; EXCISION; CARE AB Objective: The use of image guidance for sinonasal and skull base surgery has been well-characterized in adults but there is limited information on the use of these systems in the pediatric population, despite their widespread use. The aim of this study is to evaluate the use of image guidance systems to facilitate an endoscopic minimally invasive approach to sinonasal and skull base surgery in a pediatric population. Methods: A retrospective cohort study was performed at a tertiary pediatric hospital. Thirty-three children presented with complications of sinusitis, tumors, traumatic, or congenital lesions of the skull base and underwent endoscopic surgery using image guidance from March 2000 to April 2007. Patient variables including diagnosis, extent of disease, and complications were extracted from paper and computer charts. Additional surgical variables including set-up time, accuracy, surgeon satisfaction index and number of uses per case were also reviewed. Results: Twenty-eight patients (85%) underwent sinonasal surgery and five (15%) underwent skull base surgery. Indications included infectious complications of acute sinusitis (N = 15), neoplasms (N = 12), choanal atresia (N = 4), and cerebrospinal fluid leak (N = 2). Thirty-one patients (94%) required only one procedure. No surgical complications were reported. Surgeon satisfaction, mean accuracy and number of uses per procedure increased over time (p < 0.05). Conclusions: Image guidance systems are safe and effective tools that facilitate a minimally invasive approach to sinonasal and skull base surgery in children. Consistent with adult literature, usage and surgeon comfort increased with experience. The additional anatomical information obtained by image guidance systems facilitates a minimally invasive endoscopic approach for sinonasal and skull base pathologies. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Benoit, Margo McKenna] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Silvera, V. Michelle] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Nichollas, Richard] Hop Enfants La Timone, Serv ORL Pediat & Chirurg Cervino Faciale, Marseille, France. [Jones, Dwight; McGill, Trevor; Rahbar, Reza] Childrens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. RP Benoit, MM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Margo_Benoit@meei.harvard.edu NR 21 TC 14 Z9 15 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD OCT PY 2009 VL 73 IS 10 BP 1452 EP 1457 DI 10.1016/j.ijporl.2009.07.017 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 499UQ UT WOS:000270252100029 PM 19695718 ER PT J AU Jin, YP Arita, M Zhang, Q Saban, DR Chauhan, SK Chiang, N Serhan, CN Dana, R AF Jin, Yiping Arita, Makoto Zhang, Qiang Saban, Daniel R. Chauhan, Sunil K. Chiang, Nan Serhan, Charles N. Dana, Reza TI Anti-angiogenesis Effect of the Novel Anti-inflammatory and Pro-resolving Lipid Mediators SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; LIPOXIN A(4); CORNEAL NEOVASCULARIZATION; IN-VIVO; INFLAMMATION; RECEPTOR; LIGAND; RESOLUTION; INHIBITION AB PURPOSE. Resolvins and lipoxins are lipid mediators generated from essential polyunsaturated fatty acids that are the first dual anti-inflammatory and pro-resolving signals identified in the resolution phase of inflammation. Here the authors investigated the potential of aspirin-triggered lipoxin (LX) A4 analog (ATLa), resolving (Rv) D1, and RvE1, in regulating angiogenesis in a murine model. METHODS. ATLa and RvE1 receptor expression was tested in different corneal cell populations by RT-PCR. Corneal neovascularization (CNV) was induced by suture or micropellet (IL1-1 beta, VEGF-A) placement. Mice were then treated with ATLa, RvD1, RvE1, or vehicle, subconjunctivally at 48-hour intervals. Infiltration of neutrophils and macrophages was quantified after immunofluorescence staining. The mRNA expression levels of inflammatory cytokines, VEGFs, and VEGFRs were analyzed by real-time PCR. CNV was evaluated intravitally and morphometrically. RESULTS. The receptors for LXA4, ALX/Fpr-rs-2 and for RvE1, ChemR23 were each expressed by epithelium, stromal keratocytes, and infiltrated CD11b(+) cells in corneas. Compared to the vehicle-treated eye, ATLa-, RvD1-, and RvE1-treated eyes had reduced numbers of infiltrating neutrophils and macrophages and reduced mRNA expression levels of TNF-alpha, IL-1 alpha, IL-1 beta, VEGF-A, VEGF-C, and VEGFR2. Animals treated with these mediators had significantly suppressed suture-induced or IL-1 beta-induced hemangiogenesis (HA) but not lymphangiogenesis. Interestingly, only the application of ATLa significantly suppressed VEGF-A-induced HA. CONCLUSIONS. ATLa, RvE1, and RvD1 all reduce inflammatory corneal HA by early regulation of resolution mechanisms in innate immune responses. In addition, ATLa directly inhibits VEGF-A-mediated angiogenesis and is the most potent inhibitor of NV among this new genus of dual anti-inflammatory and pro-resolving lipid mediators. (Invest Ophthalmol Vis Sci. 2009;50:4743-4752) DOI: 10.1167/iovs.08-2462 C1 [Jin, Yiping; Zhang, Qiang; Saban, Daniel R.; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Jin, Yiping; Zhang, Qiang; Saban, Daniel R.; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Arita, Makoto; Chiang, Nan; Serhan, Charles N.] Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Brigham & Womens Hosp,Sch Med, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health [R01-EY 12963, GM38675 (CNS), P50 DE0169191 (CNS)]; Department of Defense [W81XWH- 07-2-0038]; New England Eye Bank Corneal Transplantation Research Fund; National Institutes of Health/National Center for Research Resources [P20 RR20753] FX Supported by National Institutes of Health Grant R01-EY 12963 (RD); Department of Defense Grant W81XWH- 07-2-0038 (RD); New England Eye Bank Corneal Transplantation Research Fund (RD); National Institutes of Health/National Center for Research Resources P20 RR20753 Planning Grant for Research on Blinding Eye Diseases (RD); and National Institutes of Health Grants GM38675 (CNS) and P50 DE0169191 (CNS). NR 42 TC 78 Z9 85 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2009 VL 50 IS 10 BP 4743 EP 4752 DI 10.1167/iovs.08-2462 PG 10 WC Ophthalmology SC Ophthalmology GA 497XE UT WOS:000270097200031 PM 19407006 ER PT J AU Iliaki, E Poulaki, V Mitsiades, N Mitsiades, CS Miller, JW Gragoudas, ES AF Iliaki, Eirini Poulaki, Vassiliki Mitsiades, Nicholas Mitsiades, Constantine S. Miller, Joan W. Gragoudas, Evangelos S. TI Role of alpha 4 Integrin (CD49d) in the Pathogenesis of Diabetic Retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CELL-DERIVED FACTOR-1-ALPHA; ADHESION MOLECULES; UP-REGULATION; LYMPHOCYTE ADHESION; LEUKOCYTE ADHESION; EXPRESSION; INFLAMMATION; FIBRONECTIN; ENDOTHELIUM; INHIBITION AB PURPOSE. The pathophysiology of diabetic retinopathy is mediated by leukocyte adhesion to the vascular endothelium of the diabetic retina, which results in endothelial injury, blood-retina barrier breakdown, and capillary nonperfusion. Leukocyte adhesion is triggered by the interaction of vascular endothelium adhesion molecules, such as ICAM-1, with leukocyte integrins, such as CD18. Inhibition of ICAM-1/CD18 signaling suppresses but does not completely abolish the cardinal manifestations of diabetic retinopathy, suggesting a role for additional adhesion molecules. Integrin alpha 4 (CD49d), in complex with integrin beta 1, forms very late antigen-4 (VLA-4), which interacts with vascular cell adhesion molecule-1. The authors have now studied the role of integrin alpha 4/CD49d in the pathogenesis of diabetic retinopathy. METHODS. Diabetes mellitus was induced in Long Evans rats with streptozotocin, and an anti-alpha 4 integrin/CD49d neutralizing antibody was injected 5 and 10 days later. Two weeks after streptozotocin administration, vascular leakage was quantified with the Evans Blue technique. Leukostasis was measured with a static adhesion assay ex vivo and the FITC-lectin perfusion method in vivo. Retinal VEGF and TNF-alpha levels and NF-kappa B activity were measured by ELISA. RESULTS. Blockade of alpha 4 integrin/CD49d attenuated the diabetes- induced upregulation of NF-kappa B activation, VEGF, and TNF-alpha protein levels and reduced significantly diabetes-induced leukocyte adhesion and vascular leakage. CONCLUSIONS. These data identify alpha 4 integrin/CD49d as a mediator of leukocyte adhesion and the resultant early signature abnormalities of diabetic retinopathy. Inhibition of this signaling pathway may hold promise for clinical activity in patients with diabetes. (Invest Ophthalmol Vis Sci.2009;50:4898-4904) DOI: 10.1167/iovs.08-2013 C1 [Iliaki, Eirini; Poulaki, Vassiliki; Miller, Joan W.; Gragoudas, Evangelos S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Angiogenesis Lab, Boston, MA 02114 USA. [Iliaki, Eirini; Poulaki, Vassiliki; Miller, Joan W.; Gragoudas, Evangelos S.] Harvard Univ, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. [Mitsiades, Nicholas; Mitsiades, Constantine S.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02114 USA. RP Poulaki, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Angiogenesis Lab, 243 Charles St, Boston, MA 02114 USA. EM poulakiv@gmail.com FU Knights Templar Fellowships; Massachusetts Lions Foundation FX Supported by Knights Templar Fellowships (EI, VP) and the Massachusetts Lions Foundation. NR 39 TC 22 Z9 23 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2009 VL 50 IS 10 BP 4898 EP 4904 DI 10.1167/iovs.08-2013 PG 7 WC Ophthalmology SC Ophthalmology GA 497XE UT WOS:000270097200050 PM 19553613 ER PT J AU Chen, L Sham, CW Chan, AM Francisco, LM Wu, Y Mareninov, S Sharpe, AH Freeman, GJ Yang, XJ Braun, J Gordon, LK AF Chen, Ling Sham, Caroline W. Chan, Ann M. Francisco, Loise M. Wu, Yin Mareninov, Sergey Sharpe, Arlene H. Freeman, Gordon J. Yang, Xian-Jie Braun, Jonathan Gordon, Lynn K. TI Role of the Immune Modulator Programmed Cell Death-1 during Development and Apoptosis of Mouse Retinal Ganglion Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NEUROTROPHIC FACTOR; IN-VIVO; PD-1; DIFFERENTIATION; EXPRESSION; RESPONSES; SURVIVAL; SYNAPSE; CNS; DEGENERATION AB PURPOSE. Mammalian programmed cell death (PD)-1 is a membrane-associated receptor regulating the balance between T-cell activation, tolerance, and immunopathology; however, its role in neurons has not yet been defined. The hypothesis that PD-1 signaling actively promotes retinal ganglion cell (RGC) death within the developing mouse retina was investigated. METHODS. Mature retinal cell types expressing PD-1 were identified by immunofluorescence staining of vertical retina sections; developmental expression was localized by immunostaining and quantified by Western blot analysis. PD-1 involvement in developmental RGC survival was assessed in vitro using retinal explants and in vivo using PD-1 knockout mice. PD-1 ligand gene expression was detected by RT-PCR. RESULTS. PD-1 is expressed in most adult RGCs and undergoes dynamic upregulation during the early postnatal window of retinal cell maturation and physiological programmed cell death (PCD). In vitro blockade of PD-1 signaling during this time selectively increases the survival of RGCs. Furthermore, PD-1-deficient mice show a selective increase in RGC number in the neonatal retina at the peak of developmental RGC death. Lastly, gene expression of the immune PD-1 ligand genes Pdcd1lg1 and Pdcd1lg2 was found throughout postnatal retina maturation. CONCLUSIONS. These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation. (Invest Ophthalmol Vis Sci. 2009; 50: 4941-4948) DOI: 10.1167/iovs.09-3602 C1 [Chen, Ling; Chan, Ann M.; Mareninov, Sergey; Yang, Xian-Jie; Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Chen, Ling] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Sham, Caroline W.; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Francisco, Loise M.; Wu, Yin; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Francisco, Loise M.; Wu, Yin; Sharpe, Arlene H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu OI Vargason, Caroline/0000-0001-6314-8334 FU Research to Prevent Blindness Foundation; National Institutes of Health (NIH) [T32 GM08042, PO1 AI056299]; UCLA Medical Scientist Training Program; NIH/ National Institute of Allergy and Infectious Diseases [RO1 AI021256]; UCLA Immunopathology Training Grant FX Supported by the Research to Prevent Blindness Foundation (LKG); a generous gift from Richard and Barbara Braun (LC); National Institutes of Health (NIH) Grant T32 GM08042, UCLA Medical Scientist Training Program (CWS); NIH/ National Institute of Allergy and Infectious Diseases Grant RO1 AI021256, UCLA Immunopathology Training Grant (CWS); and NIH Grant PO1 AI056299 (AHS, GJF). NR 43 TC 6 Z9 8 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2009 VL 50 IS 10 BP 4941 EP 4948 DI 10.1167/iovs.09-3602 PG 8 WC Ophthalmology SC Ophthalmology GA 497XE UT WOS:000270097200055 PM 19420345 ER PT J AU Morales, SA Mareninov, S Coulam, P Wadehra, M Goodglick, L Braun, J Gordon, LK AF Morales, Shawn A. Mareninov, Sergey Coulam, Paige Wadehra, Madhuri Goodglick, Lee Braun, Jonathan Gordon, Lynn K. TI Functional Consequences of Interactions between FAK and Epithelial Membrane Protein 2 (EMP2) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FOCAL ADHESION KINASE; COLLAGEN GEL CONTRACTION; TYROSINE PHOSPHORYLATION; PROLIFERATIVE VITREORETINOPATHY; SURFACE EXPRESSION; GROWTH-FACTOR; TETRASPANIN FUNCTIONS; ADJUNCTIVE TREATMENT; SIGNALING PATHWAYS; SWISS 3T3-CELLS AB PURPOSE. Collagen gel contraction by ARPE-19 is controlled by epithelial membrane protein 2 (EMP2) through focal adhesion kinase (FAK) activation. The purpose of this study was to test the role of EMP2 in the cellular context of FAK activation. METHODS. The ARPE-19 cell line was recombinantly modified to increase the expression of EMP2 and was used in this study. Quantification of FAK and Src phosphorylation was determined with Western blot analysis of whole cell lysates with the use of specific antibodies for different target sites of phosphorylation. Coimmunoprecipitation of whole cell lysates with an antibody against EMP2, followed by Western blot analysis and identification of FAK, was performed. Focal adhesions and their relationship to EMP2 were identified with immunofluorescence and confocal microscopy. F-actin distribution was identified using fluorescence microscopy, and alpha-smooth muscle actin (alpha-SMA) expression was quantified with Western blot analysis and specific antibodies. Adhesion to collagen type I was determined with a binding assay. RESULTS. EMP2 overexpression led to increased FAK phosphorylation at all measured phosphorylation sites. Coimmunoprecipitation and confocal microscopy provided evidence for a physical association between EMP2 and FAK. Increased EMP2 was also associated with altered distribution of focal adhesions, changes in actin organization, increased alpha-SMA expression, and increased adherence to a collagen-coated surface. CONCLUSIONS. The EMP2-FAK association represents a novel protein-protein interaction, not previously reported, that demonstrates significant functional cellular responses in the context of in vitro models of proliferative vitreoretinopathy (PVR). (Invest Ophthalmol Vis Sci. 2009;50:4949-4956) DOI: 10.1167/iovs.08-3315 C1 [Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Morales, Shawn A.; Coulam, Paige; Wadehra, Madhuri; Goodglick, Lee; Braun, Jonathan] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu FU Veterans Administration Merit Grant; American Health Assistance Foundation; NIH [AI52031, HD48540, EY007026]; Ruzic Foundation FX Supported by Veterans Administration Merit Grant (LKG), the American Health Assistance Foundation (LKG), NIH Grants AI52031 (SAM), HD48540 (JB), and EY007026 (SAM), and the Ruzic Foundation (JB). NR 44 TC 14 Z9 17 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2009 VL 50 IS 10 BP 4949 EP 4956 DI 10.1167/iovs.08-3315 PG 8 WC Ophthalmology SC Ophthalmology GA 497XE UT WOS:000270097200056 PM 19494199 ER PT J AU Nahrendorf, M Keliher, E Panizzi, P Zhang, HW Hembrador, S Figueiredo, JL Aikawa, E Kelly, K Libby, P Weissleder, R AF Nahrendorf, Matthias Keliher, Edmund Panizzi, Peter Zhang, Hanwen Hembrador, Sheena Figueiredo, Jose-Luiz Aikawa, Elena Kelly, Kimberly Libby, Peter Weissleder, Ralph TI F-18-4V for PET-CT Imaging of VCAM-1 Expression in Atherosclerosis SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; inflammation; molecular imaging; PET-CT; VCAM-1 ID CELL-ADHESION MOLECULE-1; POSITRON-EMISSION-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; PLAQUE INFLAMMATION; RABBIT ATHEROMA; IN-VITRO; ACTIVATION; REJECTION; NANOPARTICLE AB OBJECTIVES The aim of this study was to iteratively develop and validate an F-18-labeled small vascular cell adhesion molecule (VCAM)-1 affinity ligand and demonstrate the feasibility of imaging VCAM-1 expression by positron emission tomography-computed tomography (PET-CT) in murine atherosclerotic arteries. BACKGROUND Hybrid PET-CT imaging allows simultaneous assessment of atherosclerotic lesion morphology (CT) and may facilitate early risk assessment in individual patients. The early induction, confinement of expression to atherosclerotic lesions, and accessible position in proximity to the blood pool render the adhesion molecule VCAM-1 an attractive imaging biomarker for inflamed atheroma prone to complication. METHODS A cyclic, a linear, and an oligomer affinity peptide, internalized into endothelial cells by VCAM-1-mediated binding, were initially derivatized with DOTA to determine their binding profiles and pharmacokinetics. The lead compound was then F-18-labeled and tested in atherosclerotic apoE(-/-) mice receiving a high-cholesterol diet as well as wild type murine models of myocardial infarction and heart transplant rejection. RESULTS The tetrameric peptide had the highest affinity and specificity for VCAM-1 (97% inhibition with soluble VCAM-1 in vitro). In vivo PET-CT imaging using F-18-4V showed 0.31 +/- 0.02 SUV in murine atheroma (ex vivo %IDGT 5.9 +/- 1.5). F-18-4V uptake colocalized with atherosclerotic plaques on Oil Red O staining and correlated to mRNA levels of VCAM-1 measured by quantitative reverse transcription polymerase chain reaction (R = 0.79, p = 0.03). Atherosclerotic mice receiving an atorvastatin-enriched diet had significantly lower lesional uptake (p = 0.05). Furthermore, F-18-4V imaging in myocardial ischemia after coronary ligation and in transplanted cardiac allografts undergoing rejection showed high in vivo PET signal in inflamed myocardium and good correlation with ex vivo measurement of VCAM-1 mRNA by quantitative polymerase chain reaction. CONCLUSIONS F-18-4V allows noninvasive PET-CT imaging of VCAM-1 in inflammatory atherosclerosis, has the dynamic range to quantify treatment effects, and correlates with inflammatory gene expression. (J Am Coll Cardiol Img 2009; 2: 1213-22) (C) 2009 by the American College of Cardiology Foundation C1 [Nahrendorf, Matthias; Keliher, Edmund; Figueiredo, Jose-Luiz; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02124 USA. [Nahrendorf, Matthias; Libby, Peter; Weissleder, Ralph] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA. [Nahrendorf, Matthias; Keliher, Edmund; Panizzi, Peter; Zhang, Hanwen; Hembrador, Sheena; Figueiredo, Jose-Luiz; Aikawa, Elena; Kelly, Kimberly; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Nahrendorf, Matthias; Keliher, Edmund; Panizzi, Peter; Zhang, Hanwen; Hembrador, Sheena; Figueiredo, Jose-Luiz; Aikawa, Elena; Kelly, Kimberly; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, CPZN-5206,185 Cambridge St, Boston, MA 02124 USA. EM rweissleder@mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU D.W. Reynolds Foundation [UO1-HL080731, R01-HL078641, R24-CA92782] FX This work was funded in part by the D.W. Reynolds Foundation (to Drs. Libby and Weissleder), UO1-HL080731 (to Dr. Weissleder), R01-HL078641 (to Dr. Weissleder), and R24-CA92782 (to Dr. Weissleder). Drs. Keliher, Panizzi, and Zhang contributed equally to this article. NR 33 TC 101 Z9 106 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD OCT PY 2009 VL 2 IS 10 BP 1213 EP 1222 DI 10.1016/j.jcmg.2009.04.016 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 725OS UT WOS:000287655700011 PM 19833312 ER PT J AU Goodchild, TT Robinson, KA Pang, WX Tondato, F Cui, JH Arrington, J Godwin, L Ungs, M Carlesso, N Weich, N Poznansky, MC Chronos, NAF AF Goodchild, Traci T. Robinson, Keith A. Pang, Wenxin Tondato, Fernando Cui, Jianhua Arrington, Johnail Godwin, Lisa Ungs, Mark Carlesso, Nadia Weich, Nadine Poznansky, Mark C. Chronos, Nicolas A. F. TI Bone Marrow-Derived B Cells Preserve Ventricular Function After Acute Myocardial Infarction SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE stem cells; myocardial infarction; cell therapy; regenerative medicine; myocardial repair ID ENDOTHELIAL PROGENITOR CELLS; HEMATOPOIETIC STEM-CELLS; ISCHEMIC-MYOCARDIUM; HEART-FAILURE; NEOVASCULARIZATION; TRANSPLANTATION; CARDIOMYOCYTES; REGENERATION; IMPLANTATION; ANGIOBLASTS AB Objectives In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction. Background Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes. Methods Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 x 10(6) cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis. Results Fractional ventricular diameter shortening was significantly improved compared with saline (38 +/- 3.2%) when B cells alone were injected fresh (44 +/- 3.0%, p = 0.035), or after overnight culture (51 +/- 2.9%, p < 0.001), or after culture with c-kit+ cells (44 +/- 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 +/- 1.2% vs. 12.6 +/- 2.0%, p = 0.005). Conclusions Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population. (J Am Coll Cardiol Intv 2009; 2:1005-16) (c) 2009 by the American College of Cardiology Foundation C1 [Goodchild, Traci T.; Robinson, Keith A.; Pang, Wenxin; Tondato, Fernando; Cui, Jianhua; Godwin, Lisa; Chronos, Nicolas A. F.] St Josephs Translat Res Inst, Atlanta, GA 30342 USA. [Goodchild, Traci T.; Pang, Wenxin; Arrington, Johnail; Ungs, Mark; Weich, Nadine; Chronos, Nicolas A. F.] AC Therapeut Inc, Norcross, GA USA. [Carlesso, Nadia] Indiana Sch Med, Indianapolis, IN USA. [Poznansky, Mark C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Chronos, NAF (reprint author), St Josephs Translat Res Inst, 5673 Peachtree Dunwoody Rd, Atlanta, GA 30342 USA. EM nchronos@sjha.org FU AC Therapeutics, Inc.; Norcross; Georgia; The Jim Moran Foundation, Deerfield Beach, Florida FX Funding for this project was provided by AC Therapeutics, Norcross, Georgia, and The Jim Moran Foundation, Deerfield Beach, Florida. Drs. Chronos and Ungs are founders of AC Therapeutics and Drs. Goodchild and Pang and Johnail Arrington are or were employees of AC Therapeutics, Inc. Drs. Carless, Poznansky, and Welch are paid consultants for AC Therapeutics, Inc. Grant support for research was provided to Drs. Robinson, Tondato, and Cui by AC Therapeutics, Inc. Drs. Poznansky and Chronos contributed equally to this work.; The authors thank Melissa Moon for her technical assistance and Dr. Kevin Via, SJTRI Senior Research Statistician, for his statistical analysis of raw datasets. They also thank The Jim Moran Foundation for their generous support of this study. NR 31 TC 12 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD OCT PY 2009 VL 2 IS 10 BP 1005 EP 1016 DI 10.1016/j.jcin.2009.08.010 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 613IE UT WOS:000278971800017 PM 19850263 ER PT J AU Bedimo, RJ McGinnis, KA Dunlap, M Rodriguez-Barradas, MC Justice, AC AF Bedimo, Roger J. McGinnis, Kathleen A. Dunlap, Melinda Rodriguez-Barradas, Maria C. Justice, Amy C. TI Incidence of Non-AIDS-Defining Malignancies in HIV-Infected Versus Noninfected Patients in the HAART Era: Impact of Immunosuppression SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 17th International AIDS Conference CY AUG 03-08, 2008 CL Mexico City, MEXICO DE AIDS-defining malignancies; HAART; Incidence; non-AIDS-defining malignancies ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-PAPILLOMAVIRUS INFECTION; NEGATIVE WOMEN; UNITED-STATES; LUNG-CANCER; RISK; COHORT; VETERANS; TRENDS AB Background: The incidence of non-AIDS-defining malignancies (non-ADMs) is reported as unchanged or increasing in the highly active antiretroviral therapy era. Whether incidence of non-ADM is significantly higher in HIV-infected than in HIV-uninfected patients remains unclear. Methods: Incidence rates of malignancies were calculated in a cohort of veterans in care for HIV-infected and age, race, and gender-matched uninfected patients from 1997 to 2004. For HIV-infected patients, CD4 counts closest to first observation date were compared between those with and without cancer. Results: Thirty three thousand four hundred twenty HIV-infected and 66,840 HIV-uninfected patients were followed for a median of 5.1 and 6.4 years. The incidence rate ratio of HIV infected to HIV uninfected was 1.6 (1260 vs. 841 per 100,000 person-years; 95% confidence interval: 1.5 to 1.7). Incidence rate ratio for individual cancers was highest for anal cancer (14.9; confidence interval: 10.1 to 22.1). Among H W-infected patients, median CD4 counts were lower for those with non-ADM (249 vs. 270, P = 0.02), anal cancer (156 vs. 270; P < 0.001), and Hodgkin lymphoma (217 vs. 269; P = 0.03). Prostate cancer was associated with a higher CD4 count (311 vs. 266; P < 0.001). Conclusions: In the highly active antiretroviral therapy era, the incidence of non-ADMs is higher among HIV-infected than HIV-uninfected patients, adjusting for age, race, and gender. Some non-ADMs do not seem to be associated with significantly lower CD4 counts. C1 [Bedimo, Roger J.] UT SW Med Ctr, Dept Med, Vet Affairs N Texas Hlth Care Syst, Dallas, TX 75216 USA. [McGinnis, Kathleen A.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, West Haven, CT 06516 USA. [Justice, Amy C.] Yale Univ, Sch Publ Hlth, West Haven, CT 06516 USA. RP Bedimo, RJ (reprint author), UT SW Med Ctr, Dept Med, Vet Affairs N Texas Hlth Care Syst, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM roger.bedimo@va.gov FU NIAAA NIH HHS [U10 AA013566-09, U10 AA013566, 52U10 AA 13566] NR 33 TC 85 Z9 85 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2009 VL 52 IS 2 BP 203 EP 208 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 499GQ UT WOS:000270206500006 PM 19617846 ER PT J AU Kigozi, IM Dobkin, LM Martin, JN Geng, EH Muyindike, W Emenyonu, NI Bangsberg, DR Hahn, JA AF Kigozi, Isaac M. Dobkin, Loren M. Martin, Jeffrey N. Geng, Elvin H. Muyindike, Winnie Emenyonu, Nneka I. Bangsberg, David R. Hahn, Judith A. TI Late-Disease Stage at Presentation to an HIV Clinic in the Era of Free Antiretroviral Therapy in Sub-Saharan Africa SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; access; sub-Saharan Africa; late presentation ID CD4 CELL COUNTS; LATE DIAGNOSIS; MEDICAL-CARE; HIV-1-INFECTED PATIENTS; SOUTH-AFRICA; COLLABORATIVE ANALYSIS; SEROSTATUS DISCLOSURE; ALCOHOL-CONSUMPTION; INFECTED PERSONS; UNITED-STATES AB Background: Access to free antiretroviral therapy in sub-Saharan Africa has been steadily increasing, and the success of large-scale antiretroviral therapy programs depends on early initiation of HIV care. However, little is known about the stage at which those infected with HIV present for treatment in sub-Saharan Africa. Methods: We conducted a cross-sectional analysis of initial visits to the Immune Suppression Syndrome Clinic of the Mbarara University Teaching Hospital, including patients who had their initial visit between February 2007 and February 2008 (N = 2311). Results: The median age of the patients was 33 years (range 16-81 years), and 64% were female. More than one third (40%) were categorized as late presenters, that is, World Health Organization disease stage 3 or 4. Male gender, age 46-60 years (vs. younger), lower education level, being unemployed, living in a household with others, being unmarried, and lack of spousal HIV status disclosure were independently associated with late presentation, whereas being pregnant, having young children, and consuming alcohol in the prior year were associated with early presentation. Conclusions: Targeted public health interventions to facilitate earlier entry into HIV care are needed, as well as additional study to determine whether late presentation is due to delays in testing vs. delays in accessing care. C1 [Dobkin, Loren M.; Geng, Elvin H.; Hahn, Judith A.] Univ Calif San Francisco, Div Infect Dis, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Muyindike, Winnie] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. [Emenyonu, Nneka I.; Bangsberg, David R.] Harvard Univ, Sch Med, Harvard Initiat Global Hlth, Massachusetts Gen Hosp, Boston, MA USA. RP Hahn, JA (reprint author), Univ Calif San Francisco, Div Infect Dis, San Francisco Gen Hosp, UCSF Box 0811, San Francisco, CA 94143 USA. EM judy.hahn@ucsf.edu FU US National Institutes of Health [R25 MH064712, P30 MH062246, U01 A1069911, P30 A1027763, R01 MH054907]; Starr Foundation AIDS International Scholarship Fund; International AIDS Society HIV Research Trust; East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium; Antiretroviral Treatment in Lower Income Countries (ARTLINC) Collaboration; Mark and Lisa Schwartz FX Supported by the US National Institutes of Health grants R25 MH064712, P30 MH062246, U01 A1069911, P30 A1027763, and R01 MH054907; the Starr Foundation AIDS International Scholarship Fund; the International AIDS Society HIV Research Trust; the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium; the Antiretroviral Treatment in Lower Income Countries (ARTLINC) Collaboration; and Mark and Lisa Schwartz. NR 62 TC 81 Z9 81 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2009 VL 52 IS 2 BP 280 EP 289 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 499GQ UT WOS:000270206500018 PM 19521248 ER PT J AU Mularski, RA Munjas, BA Lorenz, KA Sun, S Robertson, SJ Schmelzer, W Kim, AC Shekelle, PG AF Mularski, Richard A. Munjas, Brett A. Lorenz, Karl A. Sun, Su Robertson, Sandra J. Schmelzer, Wendy Kim, Adina C. Shekelle, Paul G. TI Randomized Controlled Trial of Mindfulness-Based Therapy for Dyspnea in Chronic Obstructive Lung Disease SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID GEORGES RESPIRATORY QUESTIONNAIRE; STRESS REDUCTION PROGRAM; QUALITY-OF-LIFE; PULMONARY-DISEASE; ALTERNATIVE MEDICINE; UNITED-STATES; MANAGEMENT; HEALTH; SCALES; CANCER AB Objectives: Patients with chronic obstructive lung disease (COPD) suffer from significant dyspnea and may benefit from complementary and alternative medicine (CAM) therapies aimed at mitigating symptoms. The objective of this study was to test the efficacy of a mindfulness-based breathing therapy (MBBT) on improving symptoms and health-related quality of life in those with COPD. Design: We conducted a randomized controlled trial of 8-week mindfulness-based breathing therapy (MBBT) compared to support groups to test efficacy on improving symptoms and health-related quality of life in those with COPD. Setting: The setting for this study was an academic-affiliated veterans healthcare system. Subjects: The subjects consisted of 86 patients with COPD. Interventions: MBBT included weekly meetings practicing mindfulness mediation and relaxation response. Outcome measures: The main outcome measure was a post 6-minute-walk test (6MWT) Borg dyspnea assessment. Other outcome measures included health-related quality of life measures, 6MWT distance, symptom scores, exacerbation rates, and measures of stress and mindfulness. Analysis of covariance compared differences in outcomes between groups; paired t test evaluated changes within groups. Results: Participants were predominantly elderly men with moderate to severe COPD. We found no improvements in dyspnea (post 6MWT Borg difference between the MBBT and support group was 0.3 (95% confidence interval [CI]: -1.1, 1.7). We found no differences between groups in almost all other outcome measures by either intention-to-treat analysis or within the subset that completed assigned group sessions. For the physical summary scale of the generic Short Form-36 for Veterans, the difference between outcomes favored the support group (4.3, 95% CI: 0.4, 8.1). Participant retention was low compared to mind-body trials that randomize from CAM wait lists. Conclusions: This trial found no measurable improvements in patients with COPD receiving a mindfulness-based breathing CAM therapy compared to a support group, suggesting that this intervention is unlikely to be an important therapeutic option for those with moderate-to-severe COPD. C1 [Mularski, Richard A.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97227 USA. [Mularski, Richard A.; Munjas, Brett A.; Lorenz, Karl A.; Sun, Su; Robertson, Sandra J.; Schmelzer, Wendy; Kim, Adina C.; Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Mularski, RA (reprint author), Kaiser Permanente NW, Ctr Hlth Res, 3800 N Interstate,WIN 1060, Portland, OR 97227 USA. EM Richard.A.Mularski@kpchr.org FU VA HSR&D Career Development Award FX ClinicalTrials.gov Identifier NCT00243282 NR 54 TC 24 Z9 24 U1 2 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT PY 2009 VL 15 IS 10 BP 1083 EP 1090 DI 10.1089/acm.2009.0037 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 509OP UT WOS:000271027700008 PM 19848546 ER PT J AU Jones, KM Whitbourne, SK Whitbourne, SB Skultety, KM AF Jones, Kelly M. Whitbourne, Susan Krauss Whitbourne, Stacey B. Skultety, Karyn M. TI Identity Processes and Memory Controllability in Middle and Later Adulthood SO JOURNAL OF APPLIED GERONTOLOGY LA English DT Article DE memory controllability; identity processes; adulthood ID SELF-EFFICACY; CONTROL BELIEFS; OLDER ADULTS; PERFORMANCE; METAMEMORY; COMPLAINTS; POPULATION; ESTEEM; ROLES; AGE AB Memory is a salient area of functioning in adulthood known to be influenced by beliefs about performance. To date, individual variations in memory beliefs have not been systematically examined. The present study used hierarchical linear regressions to examine the relationship between Memory Controllability Index (MCI) subscales and identity processes in 250 adults (M = 58.01, 40 to 91 years), controlling for age, gender, and self-rated health. The ability to integrate age-related changes into identity was positively related to MCI scales measuring assessment of ability, potential to improve memory, and belief in the value of using memory strategies. The identity scale measuring negative age-related changes was related to lower memory self-assessment, ability to improve, and the belief that memory decline is inevitable. Contrary to expectation, the tendency to resist making changes in identity was not related to controllability. Findings support the utility of understanding memory-related beliefs in middle and later adulthood in terms of identity processes. C1 [Jones, Kelly M.; Whitbourne, Susan Krauss] Univ Massachusetts, Amherst, MA 01003 USA. [Whitbourne, Stacey B.] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston VA Med Ctr, Boston, MA 02215 USA. [Skultety, Karyn M.] Inst Aging, San Francisco, CA USA. RP Jones, KM (reprint author), Univ Massachusetts, Amherst, MA 01003 USA. NR 32 TC 1 Z9 1 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0733-4648 J9 J APPL GERONTOL JI J. Appl. Gerontol. PD OCT PY 2009 VL 28 IS 5 BP 582 EP 599 DI 10.1177/0733464808330823 PG 18 WC Gerontology SC Geriatrics & Gerontology GA 493BS UT WOS:000269708700003 ER PT J AU Anello, A Reichenberg, A Luo, XD Schmeidler, J Hollander, E Smith, CJ Puleo, CM Kryzak, LA Silverman, JM AF Anello, Alene Reichenberg, Abraham Luo, Xiaodong Schmeidler, James Hollander, Eric Smith, Christopher J. Puleo, Connor M. Kryzak, Lauren A. Silverman, Jeremy M. TI Brief Report: Parental Age and the Sex Ratio in Autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Paternal age; Maternal age; Sex ratio; Genetics; Genomic anomalies; Copy number variants ID PERVASIVE DEVELOPMENTAL DISORDERS; PATERNAL-AGE; SPECTRUM DISORDER; RISK; CHROMOSOME; LINKAGE; BIRTH; DAMAGE; LOCI AB The male-to-female (M:F) ratio for autism spectrum disorders (ASD), typically about 4:1, appears to decrease with increasing paternal age, but this relationship has not been systematically tested. With 393 ASD cases from families with two or more ASD cases, we categorized paternal age into five age groups (< 30, 30-34, 35-39, 40-44, 45+) and found that the M:F ratio was significantly decreased with increasing paternal age groups and remained so after also adjusting for maternal age. No significant relationship between maternal age group and the M:F ratio was observed. This study suggests that the M:F ratio is reduced with increasing paternal age consistent with de novo genetic or genomic anomalies arising more frequently as men age and then conceive children. C1 [Reichenberg, Abraham; Luo, Xiaodong; Schmeidler, James; Hollander, Eric; Smith, Christopher J.; Puleo, Connor M.; Kryzak, Lauren A.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Anello, Alene] Harvard Univ, Cambridge, MA 02138 USA. RP Silverman, JM (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM jeremy.silverman@mssm.edu FU NIMH NIH HHS [U54 MH066673-05, MH-066673, MH64547, U54 MH066673, R01 MH064547-05, R01 MH064547] NR 28 TC 19 Z9 19 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD OCT PY 2009 VL 39 IS 10 BP 1487 EP 1492 DI 10.1007/s10803-009-0755-y PG 6 WC Psychology, Developmental SC Psychology GA 495TM UT WOS:000269917900011 PM 19452267 ER PT J AU O'Cleirigh, C Skeer, M Mayer, KH Safren, SA AF O'Cleirigh, Conall Skeer, Margie Mayer, Kenneth H. Safren, Steven A. TI Functional impairment and health care utilization among HIV-infected men who have sex with men: the relationship with depression and post-traumatic stress SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE HIV; Health related quality of life; Health care utilization; Depression; Post-traumatic stress ID QUALITY-OF-LIFE; HUMAN-IMMUNODEFICIENCY-VIRUS; SUBSTANCE USE DISORDERS; UNITED-STATES; SOCIAL SUPPORT; POSITIVE WOMEN; PROGRESSION; HIV/AIDS; TRAUMA; IMPACT AB This study examined the relationship of post-traumatic and depressive symptom severity with measures of health-related quality of life (HRQOL), and health care utilization in a sample of 503 HIV-infected men who have sex with men (MSM) recruited in their primary HIV care setting. Participants completed computer assisted assessments of mood and anxiety, HRQOL, and HIV treatment. Peripheral blood CD4 (T helper) lymphocyte count, plasma HIV RNA concentration, and number of medical appointments were extracted from an electronic medical record. Controlling for demographics, disease stage, and antiretroviral medication, post-traumatic stress and depression symptoms accounted for significant variation in general health estimates, and in pain, role, and work-related impairment. Additionally, in multivariable models, post-traumatic stress and depression severity accounted for significant variation in health care utilization whereas symptoms and indices of HIV disease progression did not. These results extend the current research by providing evidence of the relationship between post-traumatic stress and depression symptom severity with measures of functional impairment and health care utilization in a relatively healthy, urban cohort of HIV-infected MSM. C1 [O'Cleirigh, Conall; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [O'Cleirigh, Conall; Skeer, Margie; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Boston, MA USA. [O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Skeer, Margie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI USA. RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,BS 07B, Boston, MA 02114 USA. EM cocleirigh@partners.org FU NIMH NIH HHS [R01 MH068746, 5R01MH068746-05]; PHS HHS [H97HA01293] NR 59 TC 32 Z9 32 U1 3 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD OCT PY 2009 VL 32 IS 5 BP 466 EP 477 DI 10.1007/s10865-009-9217-4 PG 12 WC Psychology, Clinical SC Psychology GA 495RN UT WOS:000269912800006 PM 19526337 ER PT J AU Weinand, C Xu, JW Peretti, GM Bonassar, LJ Gill, TJ AF Weinand, Christian Xu, Jian Wei Peretti, Giuseppe M. Bonassar, Lawrence J. Gill, Thomas J. TI Conditions Affecting Cell Seeding Onto Three-Dimensional Scaffolds for Cellular-Based Biodegradable Implants SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE dynamic-oscillating seeding; chondrocyte; cell labeling; tissue engineering; implant; in vivo ID TISSUE-ENGINEERED CARTILAGE; MECHANICAL-PROPERTIES; HYDROSTATIC-PRESSURE; ARTICULAR-CARTILAGE; FLOW BIOREACTOR; CHONDROCYTE; POLYMER; CULTIVATION; EXPRESSION; MODEL AB Seeding cells efficiently and uniformly onto three-dimensional scaffolds is a key element for engineering tissues, particularly when only a low-number of cells is available for tissue repair and regeneration. The aim of this study was to evaluate three seeding techniques on two biocompatible scaffolds in vitro using chondrocytes as follows: (1) static; (2) modified centrifugal cell immobilization (CCI); and (3) dynamic oscillating motion. Five milliliters of media containing 5, 10, or 25 million articular, auricular, or costal chondrocytes were used to seed porous PLGA scaffolds and sections of devitalized cartilage. The dynamic oscillating technique resulted in up to 150% higher cellular load at 7 days than CCI seeding. Cell distribution was more homogeneous throughout the scaffold under dynamic conditions versus more sporadic and dispersed cell concentrations on the scaffolds when using either the static or the modified CCI technique. Cell load and distribution, when using a low numbers of chondrocytes at one and two million cells per milliliter, was comparable to that using the much higher number, especially under dynamic seeding conditions. The seeded scaffolds were used as implants to achieve cellular bonding between two devitalized meniscus discs. The constructs were implanted subcutaneously in nude mice for 12 weeks and analyzed histologically. Implants seeded with auricular chondrocytes showed qualitative more integration into native meniscus tissue than articular and costal cell implants. We conclude the dynamic oscillating seeding technique is an efficient technique for seeding low-cell numbers onto scaffolds resulting in consistent and uniform cell distribution throughout porous PLGA scaffolds. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 91B: 80-87 2009 C1 [Weinand, Christian; Xu, Jian Wei; Peretti, Giuseppe M.; Gill, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02115 USA. [Bonassar, Lawrence J.] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. [Peretti, Giuseppe M.] Univ Vita Salute, Osped San Raffaele, Milan, Italy. RP Weinand, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02115 USA. EM chwscot@yahoo.corn RI Bonassar, Lawrence/C-2103-2016; Peretti, Giuseppe/K-6358-2016 OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 NR 20 TC 24 Z9 28 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD OCT PY 2009 VL 91B IS 1 BP 80 EP 87 DI 10.1002/jbm.b.31376 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 495MM UT WOS:000269897100010 PM 19388093 ER PT J AU Watts, NB Lewiecki, EM Bonnick, SL Laster, AJ Binkley, N Blank, RD Geusens, PP Miller, PD Petak, SM Recker, RR Saag, KG Schousboe, J Siris, ES Bilezikian, JP AF Watts, Nelson B. Lewiecki, E. Michael Bonnick, Sydney L. Laster, Andrew J. Binkley, Neil Blank, Robert D. Geusens, Piet P. Miller, Paul D. Petak, Steven M. Recker, Robert R. Saag, Kenneth G. Schousboe, John Siris, Ethel S. Bilezikian, John P. TI Clinical Value of Monitoring BMD in Patients Treated With Bisphosphonates for Osteoporosis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID BONE-MINERAL DENSITY; FRACTURE INTERVENTION TRIAL; POSTMENOPAUSAL OSTEOPOROSIS; VERTEBRAL FRACTURES; RANDOMIZED-TRIAL; TURNOVER MARKERS; WOMEN; ALENDRONATE; THERAPY; RISK C1 [Watts, Nelson B.] Univ Cincinnati, Bone Hlth & Osteoporosis Ctr, Cincinnati, OH 45219 USA. [Lewiecki, E. Michael] Univ New Mexico, Sch Med, New Mexico Clin Res & Osteoporosis Ctr, Albuquerque, NM 87131 USA. [Bonnick, Sydney L.] Clin Res Ctr N Texas, Denton, TX USA. [Laster, Andrew J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Blank, Robert D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Sect Endocrinol Diabet & Metab, Madison, WI USA. [Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Geusens, Piet P.] Maastricht Univ, Med Ctr, Dept Internal Med, Subdiv Rheumatol, Maastricht, Netherlands. [Geusens, Piet P.] Univ Hasselt, Biomed Res Inst, Hasselt, Belgium. [Miller, Paul D.] Colorado Ctr Bone Res, Lakewood, CO USA. [Petak, Steven M.] Texas Inst Reprod Med & Endocrinol, Houston, TX USA. [Recker, Robert R.] Creighton Univ, Sch Med, Osteoporosis Res Ctr, Omaha, NE USA. [Saag, Kenneth G.] Univ Alabama Birmingham, Ctr Educ & Res Therapeut Musculoskeletal Disorder, Birmingham, AL USA. [Saag, Kenneth G.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Ctr Outcomes Effectiveness Res & Educ, Birmingham, AL 35294 USA. [Schousboe, John] Univ Minnesota, Div Hlth Pol & Management, Pk Nicollet Hlth Serv, Minneapolis, MN USA. [Siris, Ethel S.] Columbia Univ, Med Ctr, Tony Stabile Osteoporosis Ctr, New York, NY USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, Dept Med, Div Endocrinol, New York, NY USA. RP Watts, NB (reprint author), Univ Cincinnati, Bone Hlth & Osteoporosis Ctr, 222 Piedmont Rd,Suite 6300, Cincinnati, OH 45219 USA. EM nelson.watts@uc.edu OI Blank, Robert Daniel/0000-0003-2950-1944 FU AHRQ HHS [U18 HS016956] NR 31 TC 29 Z9 30 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2009 VL 24 IS 10 BP 1643 EP 1646 DI 10.1359/JBMR.090818 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 503HC UT WOS:000270523300002 PM 19712042 ER PT J AU Burnett-Bowie, SAM Henao, MP Dere, ME Lee, H Leder, BZ AF Burnett-Bowie, Sherri-Ann M. Henao, Maria P. Dere, Melissa E. Lee, Hang Leder, Benjamin Z. TI Effects of hPTH(1-34) Infusion on Circulating Serum Phosphate, 1,25-Dihydroxyvitamin D, and FGF23 Levels in Healthy Men SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibroblast growth factor 23; phosphate; 1,25-dihydroxyvitamin D; PTH ID FIBROBLAST GROWTH FACTOR-23; PARATHYROID-HORMONE; PRIMARY HYPERPARATHYROIDISM; SKELETAL SENSITIVITY; DIETARY PHOSPHATE; VITAMIN-D; FGF-23; FIBROBLAST-GROWTH-FACTOR-23; METABOLISM; OSTEOMALACIA AB Fibroblast growth factor 23 (FGF23) promotes phosphaturia and suppresses 1,25-dihydroxyvitamin D [1,25(OH)(2)D] production. PTH also promotes phosphaturia, but, in contrast, stimulates 1,25(OH)(2)D production. The relationship between FGF23 and PTH is unclear, and the acute effect of pharmacologically dosed PTH on FGF23 secretion is unknown. Twenty healthy men were infused with human PTH(1-34) [hPTH(1-34)] at 44 ng/kg/h for 24 h. Compared with baseline, FGF23, 1,25(OH)(2)D, ionized calcium (iCa), and serum N-telopeptide (NTX) increased significantly over the 1.8-h hPTH(1-34) infusion (p < 0.0001), whereas serum phosphate (PO(4)) transiently increased and then returned to baseline. FGF23 increased from 35 +/- 10 pg/ml at baseline to 53 +/- 20 pg/ml at 18 h (p = 0.0002); 1,25(OH)(2)D increased from 36 +/- 16 pg/ml at baseline to 80 +/- 33 pg/ml at 18 h (p < 0.0001); iCa increased from 1.23 +/- 0.03 mM at baseline to 1.46 +/- 0.05 mM at hour 18 (p < 0.0001.); and NTX increased from 17 +/- 4 nM BCE at baseline to 28 +/- 8 nM BCE at peak (P < 0.0001) PO(4) was 3.3 +/- 0.6 mg/dl at baseline, transiently rose to 3.7 +/- 0.4 mg/dl at hour 6 (p = 0.016), and then returned to 3.4 +/- 0.5 mg/dl at hour 12 (p = 0.651). hPTH(1-34) infusion increases endogenous 1,25(OH)(2)D and FGF23 within 18 h in healthy men. Whereas it is possible that the rise in PO(4) contributed to the observed increase in FGF23, the increase in 1,25(OH)(2)D was more substantial and longer sustained than the change in serum phosphate. Given prior data that suggest that neither PTH nor calcium stimulate FGF23 secretion, these data support the assertion that 1,25(OH)(2)D is a potent physiologic stimulator of FGF23 secretion. J Bone Miner Res 2009;24:1681-1685. Published online on April 27, 2009; doi: 10.1359/JBMR.090406 C1 [Burnett-Bowie, Sherri-Ann M.; Henao, Maria P.; Dere, Melissa E.; Lee, Hang; Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Burnett-Bowie, SAM (reprint author), MPH, 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, K23-DK-073356-01, MOI.-RR-01066]; NIGH Physician-Scientist Development Award FX We are grateful to the staff of the MGH Mallinckrodt GCRC for the implementation of the study protocol. This work was supported by National Institute of Health Grants K23-RR-161310 (to B.Z.L.), K23-DK-073356-01 (to S.M.B.), and MOI.-RR-01066 (to the Mallinckrodt GCRC) and NIGH Physician-Scientist Development Award (to S.M.B.). NR 28 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2009 VL 24 IS 10 BP 1681 EP 1685 DI 10.1359/JBMR.090406 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 503HC UT WOS:000270523300008 PM 19419295 ER PT J AU Tondo, C Forleo, GB Pappalardo, A Heist, EK Avella, A Laurenzi, F De Girolamo, P Bencardino, G Dello Russo, A Casella, M Barret, C Ruskin, JN Mansour, M AF Tondo, C. Forleo, G. B. Pappalardo, A. Heist, E. K. Avella, A. Laurenzi, F. De Girolamo, P. Bencardino, G. Dello Russo, A. Casella, M. Barret, C. Ruskin, J. N. Mansour, M. TI A COMBINED CRYOENERGY AND RADIOFREQUENCY APPROACH TO CATHETER ABLATION OF PERSISTENT ATRIAL FIBRILLATION: PRELIMINARY RESULTS FROM A PILOT STUDY SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Meeting Abstract CT 11th International Workshop on Cardiac Arrhythmias CY OCT 04-07, 2009 CL Venice, ITALY C1 [Tondo, C.; Forleo, G. B.; Pappalardo, A.; Avella, A.; Laurenzi, F.; De Girolamo, P.; Bencardino, G.; Dello Russo, A.; Casella, M.] Univ Cattolica Sacro Cuore, St Camillo Forlanini Hosp, Cardiac Arrhythmia & Heart Failure Res Inst, I-00168 Rome, Italy. [Heist, E. K.; Barret, C.; Ruskin, J. N.; Mansour, M.] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. RI Forleo, Giovanni/G-8788-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2009 VL 20 BP S27 EP S28 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 498XO UT WOS:000270179400077 ER PT J AU King, DR Vlahakes, GJ Johri, AM Sheikh, AY AF King, David R. Vlahakes, Gus J. Johri, Amer M. Sheikh, Ahmad Y. TI Postpericardiotomy syndrome from transdiaphragmatic pericardial window following trauma: first description and review of the literature SO JOURNAL OF CARDIOVASCULAR MEDICINE LA English DT Article DE pericardial window; transdiaphragmatic; traumatic heart injury ID MYOCARDIAL-INFARCTION SYNDROME; ANTI-HEART ANTIBODIES; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; RECURRENT; DIAGNOSIS; TAMPONADE AB Diagnostic pericardial window (by either subxyphoid or transdiaphragmatic approach) is commonly utilized to exclude traumatic cardiac injury. Although regarded as a low-risk procedure, rare complications such as bacterial pericarditis, iatrogenic cardiac injury, cardiac herniation and postpericardiotomy syndrome can occur. We report the first description of postpericardiotomy syndrome following transdiaphragmatic pericardial window. J Cardiovasc Med 10:806-809 (C) 2009 Italian Federation of Cardiology. C1 [King, David R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02141 USA. [Vlahakes, Gus J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiothorac Surg, Boston, MA 02141 USA. [Johri, Amer M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cardiac Ultrasound, Boston, MA 02141 USA. [Sheikh, Ahmad Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02141 USA. RP King, DR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM Dking3@partners.org OI King, David/0000-0003-1028-1478 NR 27 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1558-2027 J9 J CARDIOVASC MED JI J. Cardiovasc. Med. PD OCT PY 2009 VL 10 IS 10 BP 806 EP 809 DI 10.2459/JCM.0b013e32832d7239 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 497GN UT WOS:000270046400014 PM 19606058 ER PT J AU Utikal, J Maherali, N Kulalert, W Hochedlinger, K AF Utikal, Jochen Maherali, Nimet Kulalert, Warakorn Hochedlinger, Konrad TI Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE Reprogramming; iPS cell; Melanocyte; Sox2 ID HUMAN SOMATIC-CELLS; HUMAN FIBROBLASTS; DEFINED FACTORS; GENERATION; MOUSE; ADULT; INDUCTION; SYSTEM; DIFFERENTIATION; NEURONS AB Induced pluripotent stem cells (iPSCs) have been derived at low frequencies from different cell types through ectopic expression of the transcription factors Oct4 and Sox2, combined with either Klf4 and c-Myc or Lin28 and Nanog. In order to generate iPSCs more effectively, it will be crucial to identify somatic cells that are easily accessible and possibly require fewer factors for conversion into iPSCs. Here, we show that both human and mouse melanocytes give rise to iPSCs at higher efficiencies than fibroblasts. Moreover, we demonstrate that a mouse malignant melanoma cell line, which has previously been reprogrammed into embryonic stem cells by nuclear transfer, remains equally amenable to reprogramming into iPSCs by these transcription factors. In contrast to skin fibroblasts, melanocytes and melanoma cells did not require ectopic Sox2 expression for conversion into iPSCs. iPSC lines from melanocytic cells expressed pluripotency markers, formed teratomas and contributed to viable chimeric mice with germ line transmission. Our results identify skin melanocytes as an alternative source for deriving patient-specific iPSCs at increased efficiency and with fewer genetic elements. In addition, our results suggest that cancer cells remain susceptible to transcription factor-mediated reprogramming, which should facilitate the study of epigenetic changes in human cancer. C1 [Utikal, Jochen; Maherali, Nimet; Kulalert, Warakorn; Hochedlinger, Konrad] Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Utikal, Jochen; Maherali, Nimet; Kulalert, Warakorn; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Utikal, Jochen] Univ Heidelberg, Dept Dermatol Venereol & Allergol, Univ Med Ctr Mannheim, D-68135 Mannheim, Germany. [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu OI Utikal, Jochen/0000-0001-5316-0241 FU Dr Mildred Scheel Foundation for Cancer Research; Natural Sciences and Engineering Research Council of Canada; Alberta Scholarships; NIH Director's Innovator Award; Harvard Stem Cell Institute; V Foundation and the Kimmel Foundation FX We thank Matthias Stadtfeld for critical review of the manuscript. We also thank Laura Prickett, Kathryn E. Folz-Donahue for help with FACS analysis and Patricia Follett for performing blastocyst injections. J.U. was supported by the Dr Mildred Scheel Foundation for Cancer Research. N.M. was supported by a graduate scholarship from the Natural Sciences and Engineering Research Council of Canada and a Sir James Lougheed Award from Alberta Scholarships. K. H. was supported by the NIH Director's Innovator Award, the Harvard Stem Cell Institute, the V Foundation and the Kimmel Foundation. This study has been approved by the MGH animal and biosafety committees. Deposited in PMC for release after 12 months. NR 43 TC 156 Z9 165 U1 4 U2 20 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT PY 2009 VL 122 IS 19 BP 3502 EP 3510 DI 10.1242/jcs.054783 PG 9 WC Cell Biology SC Cell Biology GA 494TK UT WOS:000269839900009 PM 19723802 ER PT J AU Nicosia, RF AF Nicosia, R. F. TI The aortic ring model of angiogenesis: a quarter century of search and discovery SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Review DE neovascularization; endothelial cells; mural cells; angiogenic factors; integrins; proteolytic enzymes; fibronectin; laminin; collagen; fibrin ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; ARG-GLY-ASP; 3-DIMENSIONAL EXTRACELLULAR-MATRIX; VASCULAR-PERMEABILITY FACTOR; RECEPTOR TYROSINE KINASES; FACTOR INDUCE EXPRESSION; TOLL-LIKE RECEPTORS; COLLAGEN TYPE-I; RAT AORTA AB The aortic ring model has become one of the most widely used methods to study angiogenesis and its mechanisms. Many factors have contributed to its popularity including reproducibility, cost effectiveness, ease of use and good correlation with in vivo studies. In this system aortic rings embedded in biomatrix gels and cultured under chemically defined conditions generate arborizing vascular outgrowths which can be stimulated or inhibited with angiogenic regulators. Originally based on the rat aorta, the aortic ring model was later adapted to the mouse for the evaluation of specific molecular alterations in genetically modified animals. Viral transduction of the aortic rings has enabled investigators to overexpress genes of interest in the aortic cultures. Experiments on angiogenic mechanisms have demonstrated that formation of neovessels in aortic cultures is regulated by macrophages, pericytes and fibroblasts through a complex molecular cascade involving growth factors, inflammatory cytokines, axonal guidance cues, extracellular matrix (ECM) molecules and matrix-degrading proteolytic enzymes. These studies have shown that endothelial sprouting can be effectively blocked by depleting the aortic explants of macrophages or by interfering with the angiogenic cascade at multiple levels including growth factor signalling, cell adhesion and proteolytic degradation of the ECM. In this paper, we review the literature in this field and retrace the journey from our first morphological descriptions of the aortic outgrowths to the latest breakthroughs in the cellular and molecular regulation of aortic vessel growth and regression. C1 [Nicosia, R. F.] VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA 98108 USA. [Nicosia, R. F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv S 113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@va.gov RI Perez , Claudio Alejandro/F-8310-2010; Xiao, Yang/B-5668-2012 OI Perez , Claudio Alejandro/0000-0001-9688-184X; FU Smith Charitable Trust; National Institutes of Health [HL52585]; Department of Veterans affairs FX I wish to thank all the postdoctoral fellows, technicians and collaborators who over the years have contributed to our studies on the aortic ring model and whose names are cited in the reference list. I am particularly grateful to Alfred C. Aplin, whose molecular expertise has been essential for the advances we made in recent years and who has graciously helped me with the references and the figures of this paper. I am also indebted to the W.W. Smith Charitable Trust, which funded my first studies, and the National Institutes of Health (HL52585) and the Department of Veterans affairs for their continuous support. NR 247 TC 41 Z9 41 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD OCT PY 2009 VL 13 IS 10 BP 4113 EP 4136 DI 10.1111/j.1582-4934.2009.00891.x PG 24 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 551BX UT WOS:000274181900004 PM 19725916 ER PT J AU Kwok, S Rittling, SR Partridge, NC Benson, CS Thiyagaraj, M Srinivasan, N Selvamurugan, N AF Kwok, Sukyee Rittling, Susan R. Partridge, Nicola C. Benson, Chellakkan S. Thiyagaraj, Mayuranathan Srinivasan, Narasimhan Selvamurugan, Nagarajan TI Transforming Growth Factor-beta 1 Regulation of ATF-3 and Identification of ATF-3 Target Genes in Breast Cancer Cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE TGF-B; ATF-3; CYCLIN A1; MMP-13 ID GROWTH-FACTOR-BETA; TRANSCRIPTION FACTORS; RETINOBLASTOMA GENE; SIGNALING PATHWAYS; BONE METASTASES; STRESS-RESPONSE; EXPRESSION; RUNX2; COLLAGENASE-3; TUMOR AB Transforming growth factor-beta 1 (TGF-beta 1) is a crucial molecule for stimulation of breast cancer invasion and formation of bone metastases. The molecular mechanisms of how TGF-beta 1 mediates these effects have yet to be completely determined. We have found that activating transcription factor-3 (ATF-3) is strongly stimulated and its level is sustained by TGF-beta 1 in highly invasive and metastatic human breast cancer (MDA-MB231) and in mouse mammary pad tumor cells (r3T). ATF-3 is also overexpressed in human primary breast cancer tissue. Overexpression of ATF-3 increased normal human mammary epithelial cell number and DNA synthesis suggesting a role for ATF-3 in cell proliferation. The functional role of ATF-3 in breast cancer progression was determined by the RNA interference technique. Knockdown of ATF-3 by ATF-3 shRNA in MDA-MB231 cells decreased expression of cell cycle gene, cyclin A1 in MDA-MB231 cells. ATF-3 shRNA also decreased expression of an invasive and metastatic gene, matrix metalloproteinase-13 (MMP-13; collagenase-3) in these cells. Chromatin immunoprecipitation experiments identified the direct physical interaction of ATF-3 protein on the human MMP-13 promoter. Thus, the dysregulation of ATF-3 by TGF-beta 1 is likely to activate cyclin A1 and MMP-13 genes in breast cancer cells and that would be key to the subsequent cancer cell invasion and metastasis. J. Cell. Biochem. 108: 408-414, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Benson, Chellakkan S.; Thiyagaraj, Mayuranathan; Srinivasan, Narasimhan; Selvamurugan, Nagarajan] Univ Madras Taramani, Dr ALM Post Grad Inst Basic Med Sci, Dept Endocrinol, Madras 600113, Tamil Nadu, India. [Rittling, Susan R.] Forsyth Inst, Boston, MA 02115 USA. [Kwok, Sukyee; Partridge, Nicola C.] UMDNJ, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA. RP Selvamurugan, N (reprint author), Univ Madras Taramani, Dr ALM Post Grad Inst Basic Med Sci, Dept Endocrinol, Madras 600113, Tamil Nadu, India. EM selvamn2@yahoo.com OI Chellakkan Selvanesan, Benson/0000-0001-8013-1294; Partridge, Nicola/0000-0002-5406-4814 NR 33 TC 8 Z9 8 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 1 PY 2009 VL 108 IS 2 BP 408 EP 414 DI 10.1002/jcb.22267 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 502EM UT WOS:000270438000009 PM 19582787 ER PT J AU Grant, PE Roche-Labarbe, N Surova, A Themelis, G Selb, J Warren, EK Krishnamoorthy, KS Boas, DA Franceschini, MA AF Grant, P. Ellen Roche-Labarbe, Nadege Surova, Andrea Themelis, George Selb, Juliette Warren, Elizabeth K. Krishnamoorthy, Kalpathy S. Boas, David A. Franceschini, Maria Angela TI Increased cerebral blood volume and oxygen consumption in neonatal brain injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE NIRS (near infrared spectroscopy); hypoxic ischemic injury; stroke; neonate; CBV (cerebral blood volume); CMRO(2) (cerebral metabolic rate of oxygen consumption) ID NEAR-INFRARED SPECTROSCOPY; AMPLITUDE-INTEGRATED ELECTROENCEPHALOGRAPHY; NEWBORN-INFANTS; RESOLVED SPECTROSCOPY; ELECTRICAL-ACTIVITY; ENCEPHALOPATHY; HEMODYNAMICS; HEMOGLOBIN; SATURATION; RESPONSES AB With the increasing interest in treatments for neonatal brain injury, bedside methods for detecting and assessing injury status and evolution are needed. We aimed to determine whether cerebral tissue oxygenation (StO(2)), cerebral blood volume (CBV), and estimates of relative cerebral oxygen consumption (rCMRO(2)) determined by bedside frequency-domain near-infrared spectroscopy (FD-NIRS) have the potential to distinguish neonates with brain injury from those with non-brain issues and healthy controls. We recruited 43 neonates <= 15 days old and >33 weeks gestational age (GA): 14 with imaging evidence of brain injury, 29 without suspicion of brain injury (4 unstable, 6 stable, and 19 healthy). A multivariate analysis of variance with Newman-Keuls post hoc comparisons confirmed group similarity for GA and age at measurement. StO(2) was significantly higher in brain injured compared with unstable neonates, but not statistically different from stable or healthy neonates. Brain-injured neonates were distinguished from all others by significant increases in CBV and rCMRO(2). In conclusion, although NIRS measures of StO(2) alone may be insensitive to evolving brain injury, increased CBV and rCMRO(2) seem to be useful for detecting neonatal brain injury and suggest increased neuronal activity and metabolism occurs acutely in evolving brain injury. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1704-1713; doi:10.1038/jcbfm.2009.90; published online 15 July 2009 C1 [Grant, P. Ellen] Childrens Hosp Boston, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA. [Grant, P. Ellen; Roche-Labarbe, Nadege; Surova, Andrea; Themelis, George; Selb, Juliette; Boas, David A.; Franceschini, Maria Angela] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Selb, Juliette; Boas, David A.; Franceschini, Maria Angela] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Warren, Elizabeth K.] Massachusetts Gen Hosp, Neonatal Intens Care Unit, Boston, MA 02114 USA. [Krishnamoorthy, Kalpathy S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Krishnamoorthy, Kalpathy S.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Grant, PE (reprint author), Childrens Hosp Boston, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Wolbach 303,300 Longwood Ave, Boston, MA 02115 USA. EM ellen.grant@childrens.harvard.edu RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 FU National Institute of Health and Massachusetts General Hospital [K23NS42758]; Claflin Award [RO1-HD42908]; MGH interim FX Funding sources were National Institute of Health and Massachusetts General Hospital: grant numbers K23NS42758 and Claflin Award (PE Grant); grant numbers, RO1-HD42908, Claflin Award, and MGH interim support (MA Franceschini). The authors declare no conflict of interest. The authors sincerely thank the following for their assistance: Kara Arvin, Robert Insoft, Joe Mandeville, Sol Diamond, Sara Barnett, Sonal Thaker, Eleni Themelis, Tina Chaves, Shalini Nadgir, Weichen Wu, as well as all the nurses and staff at MGH involved with neonatal care. NR 37 TC 38 Z9 41 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 IS 10 BP 1704 EP 1713 DI 10.1038/jcbfm.2009.90 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 502SE UT WOS:000270479600008 PM 19675563 ER PT J AU Badgaiyan, R Fischman, A AF Badgaiyan, R. Fischman, A. TI Study of human emotional processing using molecular imaging SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Badgaiyan, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Badgaiyan, R.] Harvard Univ, Sch Med, Boston, MA USA. [Badgaiyan, R.; Fischman, A.] Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S588 EP S588 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900722 ER PT J AU Eikermann-Haerter, K Wang, Y Ferrari, MD Van Den Maagdenberg, AMJM Moskowitz, MA Ayata, C AF Eikermann-Haerter, K. Wang, Y. Ferrari, M. D. Van Den Maagdenberg, A. M. J. M. Moskowitz, M. A. Ayata, C. TI Facilitated subcortical propagation of cortical spreading depression in familial hemiplegic migraine type 1 mutant mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Eikermann-Haerter, K.; Wang, Y.; Moskowitz, M. A.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Van Den Maagdenberg, A. M. J. M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S291 EP S292 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900353 ER PT J AU Eikermann-Haerter, K Wang, Y Dilekoz, E Arboleda-Velasquez, JF Artavanis-Tsakonas, S Joutel, A Moskowitz, MA Ayata, C AF Eikermann-Haerter, K. Wang, Y. Dilekoz, E. Arboleda-Velasquez, J. F. Artavanis-Tsakonas, S. Joutel, A. Moskowitz, M. A. Ayata, C. TI Increased susceptibility to cortical spreading depression in cadasil mutant mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Eikermann-Haerter, K.; Wang, Y.; Dilekoz, E.; Moskowitz, M. A.; Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Arboleda-Velasquez, J. F.; Artavanis-Tsakonas, S.] Harvard Univ, Sch Med, Boston, MA USA. [Joutel, A.] Univ Paris 07, Fac Med, Paris, France. [Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S53 EP S53 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900059 ER PT J AU Hoffmann, U Kudo, C Dilekoz, E Moskowitz, MA Ayata, C AF Hoffmann, U. Kudo, C. Dilekoz, E. Moskowitz, M. A. Ayata, C. TI Gabapentin acutely suppresses cortical spreading depression in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Hoffmann, U.; Kudo, C.; Dilekoz, E.; Moskowitz, M. A.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Kudo, C.] Osaka Univ, Grad Sch Dent, Dept Dent Anesthesiol, Osaka, Japan. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Charlestown, MA USA. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S290 EP S291 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900352 ER PT J AU Kronenberg, G Balkaya, M Prinz, V Gertz, K Ji, S Hoertnagl, H Waebert, C Stumm, R Endres, M AF Kronenberg, G. Balkaya, M. Prinz, V. Gertz, K. Ji, S. Hoertnagl, H. Waebert, C. Stumm, R. Endres, M. TI Beyond post-stroke depression: effects of delayed cipramil treatment on secondary exofocal postischemic degeneration and long-term stroke outcome SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Kronenberg, G.; Balkaya, M.; Prinz, V.; Gertz, K.; Ji, S.] Charite, Ctr Stroke Res Berlin, D-13353 Berlin, Germany. [Kronenberg, G.] Charite, Dept Psychiat, D-13353 Berlin, Germany. [Hoertnagl, H.] Charite, Inst Pharmacol & Toxicol, D-13353 Berlin, Germany. [Waebert, C.] Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp, Charlestown, MA USA. [Stumm, R.] Otto Von Guericke Univ, Inst Pharmacol & Toxicol, Magdeburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S77 EP S78 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900085 ER PT J AU Kudo, C Eikermann-Haerter, K Yuzawa, I Qin, T Liu, C Gu, Y Niwa, H Waeber, C Moskowitz, MA Sims, JR Ayata, C AF Kudo, C. Eikermann-Haerter, K. Yuzawa, I. Qin, T. Liu, C. Gu, Y. Niwa, H. Waeber, C. Moskowitz, M. A. Sims, J. R. Ayata, C. TI Chronic cerebral hypoperfusion model in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Kudo, C.; Eikermann-Haerter, K.; Yuzawa, I.; Qin, T.; Gu, Y.; Waeber, C.; Moskowitz, M. A.; Sims, J. R.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Kudo, C.; Niwa, H.] Osaka Univ, Grad Sch Dent, Dept Dent Anesthesiol, Osaka, Japan. [Liu, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sims, J. R.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv,Dept Neurol, Charlestown, MA USA. [Sims, J. R.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S409 EP S410 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900495 ER PT J AU Lee, JH Eikermann-Haerter, K Joutel, A Moskowitz, MA Ayata, C AF Lee, J. H. Eikermann-Haerter, K. Joutel, A. Moskowitz, M. A. Ayata, C. TI Enlarged infarcts in mice expressing the archetypal NOTCH3 R90C cadasil mutation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism ID AUTOSOMAL-DOMINANT ARTERIOPATHY; SUBCORTICAL INFARCTS; LEUKOENCEPHALOPATHY C1 [Lee, J. H.; Eikermann-Haerter, K.; Moskowitz, M. A.; Ayata, C.] Harvard Univ, Sch Med, Stroke & Neurovascular Regulat Lab, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA USA. [Joutel, A.] Univ Paris 07, Fac Med, Paris, France. [Ayata, C.] Harvard Univ, Sch Med, Stroke Serv, Charlestown, MA USA. [Ayata, C.] Harvard Univ, Sch Med, Neurosci Intens Care Unit, Dept Neurol, Charlestown, MA USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S253 EP S254 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900306 ER PT J AU Liu, PK You, Z Liu, CH AF Liu, P. K. You, Z. Liu, C. H. TI Brain probes for MRI of de novo neural progenitor cells in live brains after global cerebral ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Liu, P. K.; You, Z.; Liu, C. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S376 EP S376 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900453 ER PT J AU Normandin, MD Badgaiyan, RD Morris, ED AF Normandin, M. D. Badgaiyan, R. D. Morris, E. D. TI Spatio-temporal mapping of neurotransmitter activation using a linearization of the parametric ntPET model SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Normandin, M. D.; Morris, E. D.] Indiana Univ, Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. [Normandin, M. D.; Morris, E. D.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Badgaiyan, R. D.] Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. [Morris, E. D.] Indiana Univ Purdue Univ, Dept Biomed Engn, Purdue Sch Engn & Technol, Indianapolis, IN 46202 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S319 EP S320 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900389 ER PT J AU Radhakrishnan, H Thakur, K Wu, W Ruvinskaya, S Marota, J Boas, D Franceschini, MA AF Radhakrishnan, H. Thakur, K. Wu, W. Ruvinskaya, S. Marota, J. Boas, D. Franceschini, M. A. TI Effect of different anesthetics on neurovascular coupling SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism ID SOMATOSENSORY CORTEX; BLOOD-FLOW; ACTIVATION; RAT C1 [Radhakrishnan, H.; Thakur, K.; Wu, W.; Ruvinskaya, S.; Marota, J.; Boas, D.; Franceschini, M. A.] Massachusetts Gen Hosp, Radiol Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S187 EP S188 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900221 ER PT J AU Sakadzic, S Srinivasan, VJ Yaseen, MA Devor, A Ayata, C Boas, DA AF Sakadzic, S. Srinivasan, V. J. Yaseen, M. A. Devor, A. Ayata, C. Boas, D. A. TI Two-photon measurement and modeling of NADH emission changes in cortex during hypoxia, cortical spreading depression, and functional activation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Sakadzic, S.; Srinivasan, V. J.; Yaseen, M. A.; Devor, A.; Boas, D. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinuola A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA USA. [Devor, A.] Univ Calif San Diego, Dept Neurosci & Radiol, San Diego, CA 92103 USA. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Charlestown, MA USA. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neurosci Intens Care Unit, Charlestown, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S383 EP S383 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900461 ER PT J AU Shetty, N Ratai, E Herbert, M AF Shetty, N. Ratai, E. Herbert, M. TI Need and opportunities for imaging investigation of metabolism and perfusion abnormalities in autism spectrum disorders and their relationship SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Shetty, N.; Ratai, E.; Herbert, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, TRANSCEND Res Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S577 EP S577 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900708 ER PT J AU Shim, WH Baek, KY Rosen, B Jeong, JS Kim, YR AF Shim, W. H. Baek, K. Y. Rosen, B. Jeong, J. S. Kim, Y. R. TI Comparison between BOLD and CBV fluctuations using partial directed coherence in rat brains during rest SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Shim, W. H.; Baek, K. Y.; Jeong, J. S.] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. [Rosen, B.; Kim, Y. R.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RI Jeong, Jaeseung /C-1620-2011 NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S610 EP S612 PG 3 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900746 ER PT J AU Shin, HK Huang, PL Hong, KW Kim, CD Ayata, C AF Shin, H. K. Huang, P. L. Hong, K. W. Kim, C. D. Ayata, C. TI Endothelial dysfunction abrogates the beneficial effects of normobaric hyperoxia on cerebral perfusion and tissue outcome after focal cerebral ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Shin, H. K.] Pusan Natl Univ, Sch Oriental Med, Div Meridian & Struct Med, Yangsan Si, South Korea. [Shin, H. K.; Hong, K. W.; Kim, C. D.] Pusan Natl Univ, MRC Ischem Tissue Regenerat, Yangsan Si, South Korea. [Huang, P. L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Huang, P. L.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. [Ayata, C.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Charlestown, MA USA. [Ayata, C.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S175 EP S176 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900206 ER PT J AU Srinivasan, V Sakadzic, S Gorczynska, I Yaseen, A Fujimoto, J Boas, D AF Srinivasan, V. Sakadzic, S. Gorczynska, I. Yaseen, A. Fujimoto, J. Boas, D. TI Depth-resolved microscopy of cerebral blood flow and volume during somatosensory stimulation with doppler optical coherence tomography SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Srinivasan, V.; Sakadzic, S.; Yaseen, A.; Boas, D.] Harvard Univ, Massachusetts Gen Hosp, Photon Migrat Imaging Lab,Med Sch,MGH, MIT HMS Athinuola A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gorczynska, I.; Fujimoto, J.] MIT, Dept Elect Engn, Cambridge, MA 02139 USA. [Gorczynska, I.; Fujimoto, J.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S111 EP S112 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900122 ER PT J AU Stetler, R Cao, G Yanqin, G Zhang, F Wang, S Weng, Z Vosler, P Zhang, L Chen, J AF Stetler, R. Cao, G. Yanqin, G. Zhang, F. Wang, S. Weng, Z. Vosler, P. Zhang, L. Chen, J. TI Critical role of serine-specific phosphorylation in the activation of HSP27 and its neuroprotective effect against ischemic neuronal injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Stetler, R.; Cao, G.; Zhang, F.; Wang, S.; Weng, Z.; Vosler, P.; Zhang, L.; Chen, J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Stetler, R.; Cao, G.; Zhang, F.; Wang, S.; Chen, J.] Vet Affairs Pittsburgh Hlth Care Syst, Educ & Clin Ctr, Pittsburgh, PA USA. [Stetler, R.; Cao, G.; Yanqin, G.; Chen, J.] Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S440 EP S441 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900533 ER PT J AU Sukhotinsky, I Xu, J Sims, JR Ayata, C AF Sukhotinsky, I. Xu, J. Sims, J. R. Ayata, C. TI Cortical spreading depression recovery is modulated by tissue perfusion pressure rather than oxygenation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Sukhotinsky, I.; Xu, J.; Sims, J. R.; Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovascr Regulat Lab, Boston, MA USA. [Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA USA. [Ayata, C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Intens Care Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S293 EP S294 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900355 ER PT J AU Yaseen, M Srinivasan, V Sakadziae, S Vinogradov, S Ayata, C Boas, D AF Yaseen, M. Srinivasan, V. Sakadziae, S. Vinogradov, S. Ayata, C. Boas, D. TI Monitoring oxygen partial pressure in cerebral microvasculature with high spatial resolution using phosphorescence lifetime imaging SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Yaseen, M.; Srinivasan, V.; Sakadziae, S.; Boas, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Photon Migrat Imaging Lab, Athinuola A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA USA. [Vinogradov, S.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Charlestown, MA USA. [Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neurosci Intens Care Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S382 EP S382 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900460 ER PT J AU Yuzawa, I Shin, HK Sakadzic, S Boas, DA Ay, H Ayata, C AF Yuzawa, I. Shin, H. K. Sakadzic, S. Boas, D. A. Ay, H. Ayata, C. TI Mild induced hypertension improves blood flow via external carotid collaterals in combined distal middle cerebral and carotid occlusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Yuzawa, I.; Ayata, C.] Massachusetts Gen Hosp, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Shin, H. K.] Pusan Natl Univ, Sch Oriental Med, Div Meridian & Struct Med, Yangsan Si, South Korea. [Shin, H. K.] Pusan Natl Univ, Sch Med, MRC Ischem Tissue Regenerat, Yangsan Si, South Korea. [Sakadzic, S.; Boas, D. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH MIT HMS Athinuola A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Ay, H.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Charlestown, MA USA. [Ay, H.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S400 EP S400 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900482 ER PT J AU Yuzawa, I Eikermann-Haerter, K Sakadzic, S Boas, DA Moskowitz, MA Ayata, C AF Yuzawa, I. Eikermann-Haerter, K. Sakadzic, S. Boas, D. A. Moskowitz, M. A. Ayata, C. TI Combined laser speckle and multispectral reflectance imaging of cortical spreading depression in wild type and familial hemiplegic migraine 1 mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Yuzawa, I.; Eikermann-Haerter, K.; Moskowitz, M. A.; Ayata, C.] Massachusetts Gen Hosp, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Boas, D. A.; Ayata, C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Boas, D. A.; Ayata, C.] Harvard Univ, Sch Med, Neurosci Intens Care Unit, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA USA. [Sakadzic, S.; Boas, D. A.] MGH MIT HMS Athinuola A Martinos Ctr Biomed Imagi, Dept Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S54 EP S56 PG 3 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900061 ER PT J AU Zhang, F Wang, S Luo, Y Ji, X Memoto, EM Chen, J AF Zhang, F. Wang, S. Luo, Y. Ji, X. Memoto, E. M. Chen, J. TI When hypothermia meets hypotension and hyperglycemia: the diverse effects of adenosine 5 '-monophosphate on cerebral ischemia in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism ID MILD HYPOTHERMIA C1 [Zhang, F.; Wang, S.; Chen, J.] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA USA. [Zhang, F.; Chen, J.] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Luo, Y.; Ji, X.] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Dis Res Inst, Beijing, Peoples R China. [Luo, Y.; Ji, X.] Minist Educ, Key Lab Neurodegenerat Dis, Beijing, Peoples R China. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S181 EP S182 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900213 ER PT J AU Wilens, TE AF Wilens, Timothy E. TI Combined Pharmacotherapy in Pediatric Psychopharmacology: Friend or Foe? SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org NR 3 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2009 VL 19 IS 5 BP 483 EP 484 DI 10.1089/cap.2009.19501 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 514KC UT WOS:000271392100001 PM 19877971 ER PT J AU Wilens, TE Hammerness, P Utzinger, L Schillinger, M Georgiopoulous, A Doyle, RL Martelon, M Brodziak, K AF Wilens, Timothy E. Hammerness, Paul Utzinger, Linsey Schillinger, Mary Georgiopoulous, Anna Doyle, Robert L. Martelon, MaryKate Brodziak, Kerry TI An Open Study of Adjunct OROS-Methylphenidate in Children and Adolescents Who Are Atomoxetine Partial Responders: I. Effectiveness SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; BEHAVIOR RATING INVENTORY; EXECUTIVE FUNCTION; ADHD; PHARMACOTHERAPY; COMBINATION; PERFORMANCE; STIMULANTS AB Objective: This study evaluated the effectiveness of adding OROS methylphenidate (MPH) to children who are partial responders to atomoxetine (ATMX) in the treatment of attention-deficit/hyperactivity disorder (ADHD). Methods: This is a two-phase, 7-week, open study in children aged 6-17 years. Phase I initiated ATMX for a minimum of 4 weeks. Phase II entered partial responders to ATMX and added up to 54mg of OROS MPH to their regimen. Subjects were assessed on multiple outcomes, including ADHD, executive functioning, and adverse effects. All analyses were intent to treat, with last observation carried forward. Results: Fifty subjects who were partial responders to ATMX were treated with the combination therapy, with 41 subjects completing the entire protocol. There was a 40% reduction in their ADHD Rating Scale from the start of phase II through the end of study (from 21.14 +/- 9.9 to 12.8 +/- 9.7, t = 6.5, p<0.0001). In addition, there was a clinically significant reduction in the Clinical Global Index of ADHD severity from moderate to mild ADHD(start of phase II, 3.7; end of phase II, 2.7, 27%, t = 6.5, p<0.0001), as well as improvements in executive functioning. Conclusion: These results suggest that OROS MPH added to the regimen of partial responders to ATMX improves ADHD and executive functioning, necessitating further controlled trials. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU Ortho-McNeil Pediatrics FX Funding for this study was made through an investigator-initiated grant from Ortho-McNeil Pediatrics. NR 46 TC 25 Z9 25 U1 2 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2009 VL 19 IS 5 BP 485 EP 492 DI 10.1089/cap.2008.0125 PG 8 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 514KC UT WOS:000271392100002 PM 19877972 ER PT J AU Hammerness, P Georgiopoulos, A Doyle, RL Utzinger, L Schillinger, M Martelon, M Brodziak, K Biederman, J Wilens, TE AF Hammerness, Paul Georgiopoulos, Anna Doyle, Robert L. Utzinger, Linsey Schillinger, Mary Martelon, MaryKate Brodziak, Kerry Biederman, Joseph Wilens, Timothy E. TI An Open Study of Adjunct OROS-Methylphenidate in Children Who Are Atomoxetine Partial Responders: II. Tolerability and Pharmacokinetics SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; SALTS EXTENDED-RELEASE; DRUG-INTERACTIONS; DOSE-RESPONSE; SHORT-TERM; ADOLESCENTS; FORMULATIONS; SCHOOL; TRIAL AB Objective: The aim of this study was to evaluate the tolerability of adding OROS methylphenidate (MPH) to children who are partial responders to atomoxetine (ATMX) in the treatment of attention-deficit/hyperactivity disorder (ADHD). Methods: This was a two-phase, 7-week, open study in children aged 6-17 years. Phase 1 initiated ATMX for a minimum of 4 weeks. Phase 2 entered partial responders to ATMX and added OROS MPH to their regimen. Safety was assessed using blood pressure and heart rate measurements, electrocardiogram readings, AEs, laboratories, and ATMX levels. Results: Fifty subjects who were partial responders to ATMX received the combination therapy, with 41 subjects completing the entire protocol. As reported elsewhere (Wilens et al., 2009), OROS MPH added to partial responders of ATMX was accompanied by a 40% reduction in the ADHD rating scale score and improvements in executive functioning. However, the combination of ATMX plus OROS MPH was associated with greater rates of insomnia, irritability, and loss of appetite compared to ATMX alone. A small significant increase in diastolic blood pressure was observed during adjunctive OROS MPH, with no clinically meaningful changes in electrocardiogram (ECG) parameters during the study. ATMX levels and liver function tests did not significantly change during the combination treatment. Conclusion: Adjunct OROS MPH in ATMX partial responders yielded an additive adverse effect burden in this short-term study. Further controlled research with larger samples of children is warranted. C1 [Hammerness, Paul; Georgiopoulos, Anna; Doyle, Robert L.; Utzinger, Linsey; Schillinger, Mary; Martelon, MaryKate; Brodziak, Kerry; Biederman, Joseph; Wilens, Timothy E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU Ortho-McNeil Pediatrics FX Funding for this study was made through an investigator-initiated grant (T. Wilens) from Ortho-McNeil Pediatrics. NR 31 TC 21 Z9 21 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2009 VL 19 IS 5 BP 493 EP 499 DI 10.1089/cap.2008.0126 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 514KC UT WOS:000271392100003 PM 19877973 ER PT J AU Spencer, TJ Greenbaum, M Ginsberg, LD Murphy, WR AF Spencer, Thomas J. Greenbaum, Michael Ginsberg, Lawrence D. Murphy, William Rory TI Safety and Effectiveness of Coadministration of Guanfacine Extended Release and Psychostimulants in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; PHASE-I; CLONIDINE; ADHD; METHYLPHENIDATE; COMBINATION; QUESTIONS; SYMPTOMS AB Objective: The aim of this study was to evaluate the safety and effectiveness of guanfacine extended release (GXR) administered concomitantly with psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and suboptimal response to a psychostimulant alone. Design and Methods: This was a multicenter, open-label, 9-week, dose-escalation study of 75 subjects with ADHD treated with methylphenidate (MPH) or amphetamine (AMP) alone for at least 1 month, yet with suboptimal control of ADHD symptoms. Sixty-three subjects (84.0%) completed the study. Patients received GXR in addition to their psychostimulant. Starting with 1 mg/day, GXR was increased weekly to the highest tolerated dose (1, 2, 3, or 4 mg/day), which was maintained through week 6. GXR was then titrated downward in 1-mg weekly decrements from week 7 through week 9. Psychostimulant treatment regimens were continued until at least week 7. Main Outcome Measures: Safety assessments included adverse events (AEs), vital signs, physical examination, clinical laboratory tests, the Pediatric Daytime Sleepiness Scale, and the Pittsburgh Side Effects Rating Scale. Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV), the Conners' Parent Rating Scale-Revised Short Form, Clinical Global Impressions, Parent Global Assessment, and Child Health Questionnaire-Parent Form. Results: The most common treatment-related AEs were upper abdominal pain (25.3%), fatigue (24.0%), irritability (22.7%), headache (20.0%), and somnolence (18.7%). Most AEs were mild to moderate in severity. Investigator-rated AEs due to blood pressure decreases, heart rate, or electrocardiogram findings were infrequent. Mean changes from baseline (psychostimulant monotherapy just prior to receiving GXR) to end point in ADHD-RS-IV total score were statistically significant overall: -16.1 (p<0.0001). Significant improvement in both subscales of the ADHD-RS-IV was observed. Improvement of symptoms was observed in a majority of subjects. Conclusion: Coadministration of GXR and MPH or AMP was generally safe and associated with statistically significant and clinically meaningful ADHD symptom improvement in children and adolescents. C1 [Spencer, Thomas J.] Massachusetts Gen Hosp, Clin & Res Program, Boston, MA 02114 USA. [Spencer, Thomas J.] Harvard Univ, Sch Med, Clin & Res Program, Boston, MA 02114 USA. [Greenbaum, Michael] Capstone Clin Res, Libertyville, IL USA. [Ginsberg, Lawrence D.] Red Oak Psychiat Associates, Houston, TX USA. [Murphy, William Rory] Psychiat Associates, Overland Pk, KS USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Clin & Res Program, 55 Fruit St,WAW6A, Boston, MA 02114 USA. EM tspencer@partners.org RI Andrade, Rubian/Q-2938-2016 FU Shire Development Inc FX This study was supported by Shire Development Inc. NR 31 TC 51 Z9 53 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2009 VL 19 IS 5 BP 501 EP 510 DI 10.1089/cap.2008.0152 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 514KC UT WOS:000271392100004 PM 19877974 ER PT J AU Potter, MP Liu, HY Monuteaux, MC Henderson, CS Wozniak, J Wilens, TE Biederman, J AF Potter, Mona P. Liu, Howard Y. Monuteaux, Michael C. Henderson, Carly S. Wozniak, Janet Wilens, Timothy E. Biederman, Joseph TI Prescribing Patterns for Treatment of Pediatric Bipolar Disorder in a Specialty Clinic SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ADJUNCTIVE ANTIPSYCHOTIC TREATMENT; SUBSTANCE USE DISORDERS; FAMILIAL RISK ANALYSIS; LABEL TREATMENT TRIAL; DIVALPROEX SODIUM; DOUBLE-BLIND; ADOLESCENT MANIA; I-DISORDER; JUVENILE MANIA AB Objective: The aim of this study was to describe prescribing practices in the treatment of pediatric bipolar disorder in a university practice setting. Method: A retrospective chart review was performed on 53 youths diagnosed using Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV), criteria with bipolar spectrum disorder under the active care of child psychiatrists practicing in a pediatric psychopharmacology specialty clinic. Current medications, doses, and related adverse events were recorded. Clinicians were asked to provide a target disorder (bipolar mania/mixed state, depression, attention deficit hyperactivity disorder [ADHD], or anxiety) for each medication to the best of their ability. The Clinical Global Impressions-Severity (CGI-S) scale was used to measure severity of each disorder before treatment and the Clinical Global Impressions-Improvement (CGI-I) was used to quantify the magnitude of improvement with treatment. Meaningful improvement of the disorder was defined by CGI-I score of 1 or 2. Results: The mean number of psychotropic medications per patient was 3.0 +/- 1.6. A total of 68% of patients were treated for co-morbid disorders; 23% of patients were treated with monotherapy, primarily with second-generation antipsychotics. Mania improved in 80% of cases, mixed state improved in 57% of cases, ADHD improved in 56% of cases, anxiety improved in 61% of cases, and depression improved in 90% of cases. Conclusion: The management of pediatric bipolar disorder often requires multiple medications. For the treatment of mania/ mixed states, clinicians prescribed second-generation antipsychotics more frequently than mood stabilizers, especially in the context of monotherapy. Co-morbidity was a frequent problem with moderate success obtained with combined pharmacotherapy approaches. Further psychosocial strategies to augment pharmacotherapy may improve outcome while reducing the medication burden in pediatric bipolar disorder. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Clin Program,Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Program, Dept Psychiat, Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Clin Program,Pediat Psychopharmacol & Adult ADHD, 55 Fruit St,YAW 6A-6900, Boston, MA 02114 USA. EM jbiederman@partners.org NR 86 TC 12 Z9 12 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2009 VL 19 IS 5 BP 529 EP 538 DI 10.1089/cap.2008.0142 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 514KC UT WOS:000271392100007 PM 19877977 ER PT J AU Wozniak, J Mick, E Waxmonsky, J Kotarski, M Hantsoo, L Biederman, J AF Wozniak, Janet Mick, Eric Waxmonsky, James Kotarski, Meghan Hantsoo, Liisa Biederman, Joseph TI Comparison of Open-Label, 8-Week Trials of Olanzapine Monotherapy and Topiramate Augmentation of Olanzapine for the Treatment of Pediatric Bipolar Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MANIA RATING-SCALE; DOUBLE-BLIND; WEIGHT-GAIN; ATYPICAL ANTIPSYCHOTICS; MOOD STABILIZERS; ADOLESCENT MANIA; I DISORDER; CHILDREN; RISPERIDONE AB Background: The aim of this study was to test the efficacy and safety of olanzapine+topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents. Method: Subjects (N = 40) were outpatients of both sexes, 6-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of > 15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n = 17) or olanzapine+topiramate (n = 23). Results: Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS = 26.7 +/- 9.5; end-point YMRS = 18.2 +/- 12.5, p = 0.04) and olanzapine+topiramate (baseline YMRS = 31.3 +/- 7.9; end-point YMRS = 20.4 +/- 11.4, p = 0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions-Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3 +/- 2.1 kg and the weight gain in the olanzapine+topiramate group was statistically significantly lower, 2.6 +/- 3.6 kg. Conclusions: Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania. C1 [Wozniak, Janet] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr Outpatient Care YAW 6900, Pediat Psychopharmacol Res Dept,Dept Psychiat, Boston, MA 02114 USA. RP Wozniak, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr Outpatient Care YAW 6900, Pediat Psychopharmacol Res Dept,Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM jwozniak@partners.org OI Mick, Eric/0000-0001-8505-8145 FU Stanley Medical Research Institute; Stanley Foundation FX This work was supported by a center grant from the Stanley Medical Research Institute and a grant from the Stanley Foundation. NR 41 TC 24 Z9 25 U1 2 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2009 VL 19 IS 5 BP 539 EP 545 DI 10.1089/cap.2009.0042 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 514KC UT WOS:000271392100008 PM 19877978 ER PT J AU Wright, MJ Woo, E Schmitter-Edgecombe, M Hinkin, CH Miller, EN Gooding, AL AF Wright, Matthew J. Woo, Ellen Schmitter-Edgecombe, Maureen Hinkin, Charles H. Miller, Eric N. Gooding, Amanda L. TI The Item-Specific Deficit Approach to evaluating verbal memory dysfunction: Rationale, psychometrics, and application SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Memory; Psychometrics; Brain injury; Traumatic brain injury; Human immunodeficiency virus ID TRAUMATIC BRAIN-INJURY; NEUROPSYCHOLOGICAL TEST-PERFORMANCE; HIV-ASSOCIATED DEMENTIA; TEMPORAL-LOBE EPILEPSY; CLOSED-HEAD INJURY; EPISODIC MEMORY; PARKINSONS-DISEASE; LEARNING TEST; LONG-TERM; RETRIEVAL DEFICITS AB In the current study, we introduce the Item-Specific Deficit Approach (ISDA), a novel method for characterizing memory process deficits in list-learning data. To meet this objective, we applied the ISDA to California Verbal Learning Test (CVLT) data collected from a sample of 132 participants (53 healthy participants and 79 neurologically compromised participants). Overall, the ISDA indices measuring encoding, consolidation, and retrieval deficits demonstrated advantages over some traditional indices and indicated acceptable reliability and validity. Currently, the ISDA is intended for experimental use, although further research may support its utility for characterizing memory impairments in clinical assessments. C1 [Wright, Matthew J.; Woo, Ellen; Hinkin, Charles H.; Miller, Eric N.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Woo, Ellen] Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Los Angeles, CA USA. [Schmitter-Edgecombe, Maureen] Washington State Univ, Pullman, WA 99164 USA. [Hinkin, Charles H.; Gooding, Amanda L.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Miller, Eric N.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Wright, MJ (reprint author), Harbor UCLA Med Ctr, 1000 W Carson St,D-2 Annex,5,Box 495, Torrance, CA 90509 USA. EM mwright@labiomed.org FU Marchionne Memorial Doctoral Fellowship (Washington State University); National Institutes of Health [R03 HD35838, R01 NS47690, R01 MH585522, T32 MH019535] FX Special thanks go to Anna Curren and for her assistance. This work was supported by a Marchionne Memorial Doctoral Fellowship (Washington State University) as well as National Institutes of Health funding (R03 HD35838, R01 NS47690, R01 MH585522, and T32 MH019535). Profitable use of the item-specific deficit approach (ISDA) is under the protection of U.S. Patent No. 60/862,837. NR 68 TC 11 Z9 11 U1 3 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 2009 VL 31 IS 7 BP 790 EP 802 DI 10.1080/13803390802508918 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 500AS UT WOS:000270270000002 PM 19142773 ER PT J AU Richards, JS Peng, J Amdur, RL Mikuls, TR Hooker, RS Michaud, K Reimold, AM Cannon, GW Caplan, L Johnson, D Hines, AE Kerr, GS AF Richards, J. Steuart Peng, Justin Amdur, Richard L. Mikuls, Ted R. Hooker, Roderick S. Michaud, Kaleb Reimold, Andreas M. Cannon, Grant W. Caplan, Liron Johnson, Dannette Hines, Anne E. Kerr, Gail S. TI Dual-Energy X-Ray Absorptiometry and Evaluation of the Osteoporosis Self-Assessment Tool in Men With Rheumatoid Arthritis SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE Dual-energy X-ray absorptiometry; osteoporosis; Osteoporosis Self-Assessment Tool; rheumatoid arthritis ID ASSESSMENT SCREENING TOOL; AFRICAN-AMERICAN MEN; BONE DENSITOMETRY; BODY-COMPOSITION; RISK; WOMEN; ASSOCIATION; PERFORMANCE; VALIDATION; VETERANS AB Males with rheumatoid arthritis (RA) are at risk for osteoporosis but. infrequently undergo dual-energy X-ray absorptiometry (DXA). We examined the frequency of DXA in males enrolled in the Veterans Affairs Rheumatoid Arthritis Registry. The Osteoporosis Self-Assessment Tool (OST) index, a formula using a-e and weight, was calculated for all subjects. DXA was performed on 282 (35.5%) of the males who were younger (p < 0.01), had lower mean OST index score (p < 0.05), and were more likely to have been prescribed prednisone (p < 0.01) than subjects without DXA. Low bone mass (T-score < -1) was present in 73% of subjects with DXA; 37% of subjects with low-risk OST index scores had normal bone mineral density (BMD) compared with 5.6% of those with high-risk OST index scores (p < 0.01). There was a significant but modest correlation between BMD and the OST index (r = 0.17, p < 0.01). No OST score had a sensitivity and specificity of more than 80%. Association between OST index and BMD was strongest in non-Hispanic whites, subjects older than 60 yr, and smokers. DXA was underutilized in males with RA. The OST index correlated with low bone mass but could not reliably predict osteoporosis in this population. C1 [Richards, J. Steuart; Peng, Justin; Kerr, Gail S.] Washington DC VA Med Ctr, Rheumatol Sect, Washington, DC USA. [Richards, J. Steuart; Peng, Justin; Kerr, Gail S.] Georgetown Univ, Dept Med, Washington, DC USA. [Amdur, Richard L.] Washington DC VA Med Ctr, Res Serv, Washington, DC USA. [Amdur, Richard L.] Georgetown Univ, Dept Psychiat, Washington, DC USA. [Mikuls, Ted R.; Michaud, Kaleb] Omaha VA Med Ctr, Rheumatol Sect, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Rheumatol Sect, Omaha, NE 68182 USA. [Hooker, Roderick S.; Reimold, Andreas M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Hooker, Roderick S.; Reimold, Andreas M.] VA N Texas Hlth Care Syst, Rheumatol Sect, Dallas, TX USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Cannon, Grant W.] George E Wahlen VA Med Ctr, Rheumatol Sect, Salt Lake City, UT USA. [Caplan, Liron; Hines, Anne E.] Univ Colorado, Denver, CO 80202 USA. [Caplan, Liron; Hines, Anne E.] Denver VA Med Ctr, Rheumatol Sect, Denver, CO USA. [Johnson, Dannette] Univ Mississippi, Jackson, MI USA. [Johnson, Dannette] MS VA Med Ctr, Jackson, MI USA. RP Richards, JS (reprint author), Vet Affairs Med Ctr, Rheumatol Sect, 151K,50 Irving St NW, Washington, DC 20422 USA. EM john.richards1@va.gov FU Veterans Health Administration; Abbott Laboratories; Bristol-Myers Squibb FX This work and the VARA project are also supported in part by the Health Services Research and Development Program of the Veterans Health Administration and unrestricted support front Abbott Laboratories and Bristol-Myers Squibb. NR 24 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD OCT-DEC PY 2009 VL 12 IS 4 BP 434 EP 440 DI 10.1016/j.jocd.2009.06.003 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 519UG UT WOS:000271793600004 PM 19775920 ER PT J AU Gerchman, F Tong, J Utzschneider, KM Zraika, S Udayasankar, J McNeely, MJ Carr, DB Leonetti, DL Young, BA de Boer, IH Boyko, EJ Fujimoto, WY Kahn, SE AF Gerchman, Fernando Tong, Jenny Utzschneider, Kristina M. Zraika, Sakeneh Udayasankar, Jayalakshmi McNeely, Marguerite J. Carr, Darcy B. Leonetti, Donna L. Young, Bessie A. de Boer, Ian H. Boyko, Edward J. Fujimoto, Wilfred Y. Kahn, Steven E. TI Body Mass Index Is Associated with Increased Creatinine Clearance by a Mechanism Independent of Body Fat Distribution SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHRONIC KIDNEY-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; GLOMERULAR-FILTRATION-RATE; JAPANESE-AMERICAN MEN; STAGE RENAL-DISEASE; VISCERAL ADIPOSITY; METABOLIC SYNDROME; INSULIN-RESISTANCE; SEVERE OBESITY; SURFACE AREA AB Context: Although obesity has been, in general, associated with glomerular hyperfiltration, visceral adiposity has been suggested to be associated with reduced glomerular filtration. Objective: The aim of the study was to evaluate the differential effects of obesity and body fat distribution on glomerular filtration. Design and Setting: We conducted a cross-sectional study of the Japanese-American community in Seattle, Washington. Participants: We studied a representative sample of second-generation Japanese-American men and women with normal glucose tolerance (n = 124) and impaired glucose metabolism (impaired fasting glucose and/or impaired glucose tolerance) (n = 144) residing in King County, Washington. Main Outcome Measures: Glomerular filtration rate was estimated by 24-h urinary creatinine clearance, body size by body mass index (BMI), and intra-abdominal fat (IAF), sc fat (SCF), and lean thigh areas by CT scan. Results: Creatinine clearance was positively correlated with BMI (r = 0.429; P < 0.001), fasting glucose (r = 0.198; P < 0.001), and insulin levels (r = 0.125; P < 0.042), as well as IAF (r = 0.239; P < 0.001), SCF (r = 0.281; P < 0.001), and lean thigh (r = 0.353; P < 0.001) areas. The association between creatinine clearance and BMI remained significant after adjustments for IAF, SCF areas, and fasting insulin levels (r = 0.337; P < 0.001); whereas IAF and SCF areas were not independently associated with creatinine clearance after adjusting for BMI. Creatinine clearance increased with increasing BMI after adjusting for fasting insulin, fasting glucose, IAF and SCF areas in subjects with normal glucose tolerance (r = 0.432; P < 0.001) and impaired glucose metabolism (r = 0.471; P < 0.001). Conclusions: BMI rather than body fat distribution is an independent determinant of creatinine clearance in nondiabetic subjects. Lean body mass, rather than adiposity, may explain this association. (J Clin Endocrinol Metab 94: 3781-3788, 2009) C1 [Gerchman, Fernando; Tong, Jenny; Utzschneider, Kristina M.; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Fujimoto, Wilfred Y.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Gerchman, Fernando; Tong, Jenny; Utzschneider, Kristina M.; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Fujimoto, Wilfred Y.; Kahn, Steven E.] Univ Washington, Seattle, WA 98108 USA. [McNeely, Marguerite J.; Boyko, Edward J.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Carr, Darcy B.] Univ Washington, Div Maternal Fetal Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Young, Bessie A.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Young, Bessie A.; de Boer, Ian H.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU Department of Veterans Affairs; National Institutes of Health [DK-55460, DK02860, DK-02654, DK-35816, RR-37]; Coordination of Higher Education and Graduate Training (CAPES) in Brazil; International Scholarship Program of The Endocrine Society FX This work was supported by the Department of Veterans Affairs and National Institutes of Health Grants DK-55460, DK02860, DK-02654, DK-35816, and RR-37. F. G. was supported by a scholarship from Coordination of Higher Education and Graduate Training (CAPES) in Brazil and by the International Scholarship Program of The Endocrine Society. NR 40 TC 20 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2009 VL 94 IS 10 BP 3781 EP 3788 DI 10.1210/jc.2008-2508 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 503IE UT WOS:000270526500022 PM 19584179 ER PT J AU Bredella, MA Torriani, M Thomas, BJ Ghomi, RH Brick, DJ Gerweck, AV Miller, KK AF Bredella, Miriam A. Torriani, Martin Thomas, Bijoy J. Ghomi, Reza Hosseini Brick, Danielle J. Gerweck, Anu V. Miller, Karen K. TI Peak Growth Hormone-Releasing Hormone-Arginine-Stimulated Growth Hormone Is Inversely Associated with Intramyocellular and Intrahepatic Lipid Content in Premenopausal Women with Obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH-DEFICIENT ADULTS; MAGNETIC-RESONANCE-SPECTROSCOPY; VISCERAL ADIPOSE-TISSUE; TOTAL-BODY FAT; INSULIN SENSITIVITY; CARDIOVASCULAR RISK; GLUCOSE-METABOLISM; SKELETAL-MUSCLE; POSTMENOPAUSAL WOMEN; TRIGLYCERIDE CONTENT AB Context: Visceral adiposity is a strong determinant of GH secretion, and low endogenous GH secretion is associated with increased insulin resistance, a key component of the metabolic syndrome. Increased fat accumulation in skeletal muscle and liver may play an etiological role in the development of insulin resistance and other complications of the metabolic syndrome. Little is known about the role of decreased endogenous GH secretion in the pathogenesis of insulin resistance in obesity. Objective: To investigate the relationship between intramyocellular lipids (IMCL), intrahepatic lipids, and peak-stimulated GH in premenopausal women with obesity. Design and Setting: We conducted a cross-sectional study at a clinical translational research center. Patients: Patients included 21 premenopausal women with obesity (mean body mass index, 34.0 +/- 4.5 kg/m(2)) and 17 normal-weight controls (mean body mass index, 21.9 +/- 2.0 kg/m(2)) of comparable mean age. Main Outcomes Measures: IMCL and intrahepatic lipids were measured with proton magnetic resonance spectroscopy (1H-MRS). Body composition was measured with magnetic resonance imaging. Peak GH was measured after stimulation with GHRH-arginine. Results: Obese subjects had higher IMCL, intrahepatic lipids, abdominal and thigh fat, and thigh muscle mass compared with normal-weight controls. There were strong inverse associations between peak GH and both IMCL and intrahepatic lipids independent of age and visceral adiposity. There were positive associations between IMCL and intrahepatic lipids with measures of insulin resistance and serum triglycerides. Conclusion: In premenopausal women with obesity, peak GH is inversely associated with IMCL and intrahepatic lipids independent of age and visceral adiposity. This suggests that low GH may contribute to insulin resistance in obesity through effects on muscle and intrahepatic lipids. (J Clin Endocrinol Metab 94: 3995-4002, 2009) C1 [Bredella, Miriam A.; Torriani, Martin; Thomas, Bijoy J.; Ghomi, Reza Hosseini] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Brick, Danielle J.; Gerweck, Anu V.; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org OI Hosseini Ghomi, Reza/0000-0003-4369-8237 FU National Institutes of Health [RO1 HL-077674, M01 RR-01066, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants RO1 HL-077674, M01 RR-01066, and K23 RR-23090. NR 39 TC 32 Z9 32 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2009 VL 94 IS 10 BP 3995 EP 4002 DI 10.1210/jc.2009-0438 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 503IE UT WOS:000270526500049 PM 19602559 ER PT J AU Nathan, DG AF Nathan, David G. TI Call for a slower approach to health care reform SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article C1 [Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nathan, David G.] Childrens Hosp, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2009 VL 119 IS 10 BP 2847 EP 2848 DI 10.1172/JCI40994 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 503HA UT WOS:000270523100002 PM 20069704 ER PT J AU Kahn, CR AF Kahn, C. Ronald TI Health care reform - need for less emotion and more science SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article C1 [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2009 VL 119 IS 10 BP 2856 EP 2857 DI 10.1172/JCI41036 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 503HA UT WOS:000270523100011 PM 20069714 ER PT J AU Mandinova, A Kolev, V Neel, V Hu, B Stonely, W Lieb, J Wu, XW Colli, C Han, R Pazin, M Ostano, P Dummer, R Brissette, JL Dotto, GP AF Mandinova, Anna Kolev, Vihren Neel, Victor Hu, Bing Stonely, Wesley Lieb, Jocelyn Wu, Xunwei Colli, Claudia Han, Rong Pazin, Mike Ostano, Paola Dummer, Reinhard Brissette, Janice L. Dotto, G. Paolo TI A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR RECEPTOR; EPITHELIAL TERMINAL DIFFERENTIATION; SEBORRHEIC KERATOSES; C-JUN; MULTIPLE-MYELOMA; FGFR3 MUTATIONS; NUDE GENE; EPIDERMAL-GROWTH; EXPRESSION; PROTEIN AB Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus, we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype. C1 [Hu, Bing; Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Neel, Victor; Dotto, G. Paolo] MGH, Dept Dermatol, Boston, MA USA. [Mandinova, Anna; Kolev, Vihren; Stonely, Wesley; Lieb, Jocelyn; Wu, Xunwei; Colli, Claudia; Han, Rong; Brissette, Janice L.; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Pazin, Mike] NIA, NIH, Baltimore, MD 21224 USA. [Ostano, Paola] Fondo Edo Tempia, Lab Canc Pharmacogenom, Biella, Italy. [Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland. EM gian-paolo.dotto@unil.ch OI Han, Rong/0000-0002-5766-8277; Pazin, Michael/0000-0002-7561-3640 FU NIH [AR39190, AR054856, AR04S284, CA16038, CA73796]; Swiss National Foundation; European Union [LSHB-CT-2005-019067]; Cutaneous Biology Research Center through the MGH/Shiseido Co. Ltd. Agreement FX We thank W. Austen for human skin material, D. Prowse for the FOXN1-ER retrovirus, D. Ornitz for FGFR3 constructs, and V. Rajashekara for skillful technical help. This work was supported by NIH grants AR39190, AR054856, AR04S284, CA16038, and CA73796; by the Swiss National Foundation; by a grant from the European Union (Epistem, Sixth Framework Program, LSHB-CT-2005-019067); and in part by the Cutaneous Biology Research Center through the MGH/Shiseido Co. Ltd. Agreement. NR 61 TC 33 Z9 33 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2009 VL 119 IS 10 BP 3127 EP 3137 DI 10.1172/JCI38543 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 503HA UT WOS:000270523100045 PM 19729838 ER PT J AU Balajee, SA Kano, R Baddley, JW Moser, SA Marr, KA Alexander, BD Andes, D Kontoyiannis, DP Perrone, G Peterson, S Brandt, ME Pappas, PG Chiller, T AF Balajee, S. Arunmozhi Kano, Rui Baddley, John W. Moser, Stephen A. Marr, Kieren A. Alexander, Barbara D. Andes, David Kontoyiannis, Dimitrios P. Perrone, Giancarlo Peterson, Stephen Brandt, Mary E. Pappas, Peter G. Chiller, Tom TI Molecular Identification of Aspergillus Species Collected for the Transplant-Associated Infection Surveillance Network SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELL; INVASIVE ASPERGILLOSIS; SP NOV.; FUMIGATUS; LENTULUS; PCR AB A large aggregate collection of clinical isolates of aspergilli (n = 218) from transplant patients with proven or probable invasive aspergillosis was available from the Transplant-Associated Infection Surveillance Network, a 6-year prospective surveillance study. To determine the Aspergillus species distribution in this collection, isolates were subjected to comparative sequence analyses by use of the internal transcribed spacer and beta-tubulin regions. Aspergillus fumigatus was the predominant species recovered, followed by A. flavus and A. niger. Several newly described species were identified, including A. lentulus and A. calidoustus; both species had high in vitro MICs to multiple antifungal drugs. Aspergillus tubingensis, a member of the A. niger species complex, is described from clinical specimens; all A. tubingensis isolates had low in vitro MICs to antifungal drugs. C1 [Balajee, S. Arunmozhi; Kano, Rui; Brandt, Mary E.; Chiller, Tom] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Baddley, John W.; Pappas, Peter G.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Moser, Stephen A.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Dept Med, Birmingham, AL USA. [Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Marr, Kieren A.] Johns Hopkins Univ, Baltimore, MD USA. [Alexander, Barbara D.] Duke Univ, Durham, NC USA. [Andes, David] Univ Wisconsin, Madison, WI USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Perrone, Giancarlo] CNR, Inst Sci Food Prod, Bari, Italy. [Peterson, Stephen] USDA, Natl Ctr Agr Utilizat Res, Peoria, IL USA. RP Balajee, SA (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, Mail Stop G 11,1600 Clifton Rd, Atlanta, GA 30333 USA. EM fir3@cdc.gov RI Moser, Stephen/A-1168-2008; Perrone, Giancarlo/O-7475-2014 OI Perrone, Giancarlo/0000-0002-3841-6066 FU Nihon University in Japan; NIH [K23AI064613] FX The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. NR 18 TC 92 Z9 96 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2009 VL 47 IS 10 BP 3138 EP 3141 DI 10.1128/JCM.01070-09 PG 4 WC Microbiology SC Microbiology GA 501BC UT WOS:000270351700009 PM 19675215 ER PT J AU Jung, SW Sugimoto, M Graham, DY Yamaoka, Y AF Jung, Sung Woo Sugimoto, Mitsushige Graham, David Y. Yamaoka, Yoshio TI homB Status of Helicobacter pylori as a Novel Marker To Distinguish Gastric Cancer from Duodenal Ulcer SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GASTRODUODENAL DISEASES; CLINICAL-RELEVANCE; PROMOTING GENE; INFECTION; STRAINS; CAGA; DUPA; RISK; PATHOGENESIS; INFLAMMATION AB The hom family of Helicobacter pylori outer-membrane proteins, especially the homB gene, has been suggested as a novel virulence factor; however, the clinical association and function of this gene are still unclear. We evaluated the presence of the homA, homB, and cagA genes in 286 strains isolated from patients in the U. S. and Colombian populations (126 with gastritis, 96 with duodenal ulcer, and 64 with gastric cancer) by PCR. The results were compared with the clinical presentation and gastric injury. The prevalence of the homB gene was significantly higher in strains isolated from gastric-cancer patients (71.9%) than in those from duodenal ulcer patients (52.1%) (P = 0.012). In a multivariate analysis, the presence of the cagA gene significantly increased the risk for developing gastric cancer and duodenal ulcer, with the presence of the homB gene acting as a factor that could distinguish gastric cancer from duodenal ulcer (adjusted odds ratio, 3.033; 95% confidence interval, similar to 1.37 to similar to 6.73). cagA status was correlated with homB status (r = 0.323; P < 0.01). A histological analysis showed that cagA status was associated with inflammation and atrophy both in the antrum and in the corpus, while homB status was associated with inflammation and atrophy in the corpus. homB gene status might be susceptible to gastric-cancer development such that the homB gene is used as a factor for discriminating the risk of gastric cancer from that of duodenal ulcer. C1 [Jung, Sung Woo; Sugimoto, Mitsushige; Graham, David Y.; Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. [Jung, Sung Woo; Sugimoto, Mitsushige; Graham, David Y.; Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. [Jung, Sung Woo] Korea Univ, Coll Med, Dept Internal Med, Div Gastroenterol, Seoul 136705, South Korea. [Yamaoka, Yoshio] Oita Univ, Fac Med, Dept Environm & Prevent Med, Yufu, Japan. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, 111D,Rm 3A-320,2002 Holcombe Blvd, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs (VA) by Public Health Service [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 (VA) by Public Health Service grant DK56338, which funds the Texas Gulf Coast Digestive Diseases Center. The project was also supported by grant number DK 62813 from the NIH. NR 27 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2009 VL 47 IS 10 BP 3241 EP 3245 DI 10.1128/JCM.00293-09 PG 5 WC Microbiology SC Microbiology GA 501BC UT WOS:000270351700024 PM 19710266 ER PT J AU Baddley, JW Marr, KA Andes, DR Walsh, TJ Kauffman, CA Kontoyiannis, DP Ito, JI Balajee, SA Pappas, PG Moser, SA AF Baddley, John W. Marr, Kieren A. Andes, David R. Walsh, Thomas J. Kauffman, Carol A. Kontoyiannis, Dimitrios P. Ito, James I. Balajee, S. Arunmozhi Pappas, Peter G. Moser, Stephen A. TI Patterns of Susceptibility of Aspergillus Isolates Recovered from Patients Enrolled in the Transplant-Associated Infection Surveillance Network SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AMPHOTERICIN-B; IN-VITRO; INVASIVE ASPERGILLOSIS; CROSS-RESISTANCE; AZOLE RESISTANCE; FUMIGATUS; ITRACONAZOLE; VORICONAZOLE; TERREUS; RAVUCONAZOLE AB We analyzed antifungal susceptibilities of 274 clinical Aspergillus isolates from transplant recipients with proven or probable invasive aspergillosis collected as part of the Transplant-Associated Infection Surveillance Network (TRANSNET) and examined the relationship between MIC and mortality at 6 or 12 weeks. Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth dilution method for amphotericin B (AMB), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), and ravuconazole (RAV). The isolate collection included 181 Aspergillus fumigatus, 28 Aspergillus niger, 27 Aspergillus flavus, 22 Aspergillus terreus, seven Aspergillus versicolor, five Aspergillus calidoustus, and two Aspergillus nidulans isolates and two isolates identified as Aspergillus spp. Triazole susceptibilities were <= 4 mu g/ml for most isolates (POS, 97.6%; ITR, 96.3%; VOR, 95.9%; RAV, 93.5%). The triazoles were not active against the five A. calidoustus isolates, for which MICs were >= 4 mu g/ml. AMB inhibited 93.3% of isolates at an MIC of 1 mu g/ml. The exception was A. terreus, for which 15 (68%) of 22 isolates had MICs of >1 mu g/ml. One of 181 isolates of A. fumigatus showed resistance (MIC > 4 mu g/ml) to two of three azoles tested. Although there appeared to be a correlation of higher VOR MICs with increased mortality at 6 weeks, the relationship was not statistically significant (R(2) = 0.61; P = 0.065). Significant relationships of in vitro MIC to all-cause mortality at 6 and 12 weeks for VOR or AMB were not found. C1 [Baddley, John W.; Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Infect Dis Sect, Dept Med, Birmingham, AL USA. [Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Andes, David R.] Univ Wisconsin, Dept Med, Div Infect Dis, Madison, WI USA. [Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Kauffman, Carol A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. [Ito, James I.] City Hope Natl Med Ctr, Dept Med, Div Infect Dis, Duarte, CA 91010 USA. [Balajee, S. Arunmozhi] Ctr Dis Control & Prevent, Div Mycot Dis, Atlanta, GA USA. [Moser, Stephen A.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM jbaddley@uab.edu RI Moser, Stephen/A-1168-2008 FU NIH [K23AI064613] FX J.W.B. is sponsored in part by NIH grant K23AI064613. NR 30 TC 86 Z9 88 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2009 VL 47 IS 10 BP 3271 EP 3275 DI 10.1128/JCM.00854-09 PG 5 WC Microbiology SC Microbiology GA 501BC UT WOS:000270351700029 PM 19692558 ER PT J AU Mahlen, SD Clarridge, JE AF Mahlen, Steven D. Clarridge, Jill E., III TI Site and Clinical Significance of Alloscardovia omnicolens and Bifidobacterium Species Isolated in the Clinical Laboratory SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN DENTAL-CARIES; GEN. NOV.; DENTICOLENS AB Most of the members of the genus Bifidobacterium, including the related organism Alloscardovia omnicolens, are inhabitants of the gastrointestinal tract and oral cavity of humans and animals and have been considered nonpathogenic for humans. However, the actual site of isolation and the clinical significance of A. omnicolens and of Bifidobacterium species are unclear. This may be due in part to the difficulties in distinguishing these organisms from other genera such as Actinomyces. To determine the potential disease-causing role of these organisms, we analyzed the clinical significance of 15 A. omnicolens and Bifidobacterium isolates identified by 16S rRNA gene sequencing from a clinical laboratory. All of the organisms in this study were isolated from sterile sites or in significant numbers by standard clinical microbiological culture methods. Our 15 clinical strains fit into only four species: A. omnicolens (five isolates), Bifidobacterium scardovii (four isolates), B. longum (two isolates), and B. breve (four isolates). All five A. omnicolens isolates, one of the B. breve isolates, and three of the four B. scardovii isolates were cultured from urine at 105 CFU/ml. One B. scardovii isolate was from a patient with a genitourinary tract wound infection, two B. longum isolates were from abdominal wounds, and three B. breve isolates were from blood cultures. This study enlarges the spectrum of diseases and clinical sources associated with A. omnicolens and Bifidobacterium species and addresses identification problems. C1 [Mahlen, Steven D.] Univ Washington, Dept Lab Med, USA, Seattle, WA 98195 USA. [Clarridge, Jill E., III] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA 98108 USA. RP Clarridge, JE (reprint author), VA PSHCS, Pathol & Lab Med Serv 113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jill.clarridge@va.gov NR 13 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2009 VL 47 IS 10 BP 3289 EP 3293 DI 10.1128/JCM.00555-09 PG 5 WC Microbiology SC Microbiology GA 501BC UT WOS:000270351700032 PM 19641056 ER PT J AU Greenberg, CC Ashley, SW Schrag, D AF Greenberg, Caprice C. Ashley, Stanley W. Schrag, Deborah TI Centralization of Cancer Surgery: What Does It Mean for Surgical Training? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID OPERATIVE MORTALITY; PROCEDURE VOLUME; HOSPITAL VOLUME; UNITED-STATES C1 [Greenberg, Caprice C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Greenberg, Caprice C.; Ashley, Stanley W.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Greenberg, CC (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 75 Francis St, Boston, MA 02115 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2009 VL 27 IS 28 BP 4637 EP 4639 DI 10.1200/JCO.2009.23.0052 PG 3 WC Oncology SC Oncology GA 500LS UT WOS:000270304100003 PM 19720900 ER PT J AU Friedman, HS Prados, MD Wen, PY Mikkelsen, T Schiff, D Abrey, LE Yung, WKA Paleologos, N Nicholas, MK Jensen, R Vredenburgh, J Huang, J Zheng, MX Cloughesy, T AF Friedman, Henry S. Prados, Michael D. Wen, Patrick Y. Mikkelsen, Tom Schiff, David Abrey, Lauren E. Yung, W. K. Alfred Paleologos, Nina Nicholas, Martin K. Jensen, Randy Vredenburgh, James Huang, Jane Zheng, Maoxia Cloughesy, Timothy TI Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGRESSION-FREE SURVIVAL; PHASE-II TRIAL; MALIGNANT GLIOMA; PLUS IRINOTECAN; VEGF-A; CANCER; MULTIFORME; TEMOZOLOMIDE; EXPRESSION; THERAPY AB Purpose We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial. Patients and Methods One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review. Secondary end points included safety and overall survival. Results In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups, estimated 6-month progression-free survival rates were 42.6% and 50.3%, respectively; objective response rates were 28.2% and 37.8%, respectively; and median overall survival times were 9.2 months and 8.7 months, respectively. There was a trend for patients who were taking corticosteroids at baseline to take stable or decreasing doses over time. Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade >= 3 adverse events, the most common of which were hypertension (8.3%) and convulsion (6.0%) in the bevacizumab-alone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in the bevacizumab-plus-irinotecan group. Intracranial hemorrhage was noted in two patients (2.4%) in the bevacizumab-alone group (grade 1) and in three patients (3.8%) patients in the bevacizumab-plus-irinotecan group (grades 1, 2, and 4, respectively). Conclusion Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma. C1 Duke Univ, Brain Tumor Ctr, Durham, NC 27710 USA. Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles Sch Med, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Henry Ford Hosp, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Evanston NW Healthcare, Div Neurol, Evanston, IL USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. Univ Utah Hosp, Salt Lake City, UT USA. RP Friedman, HS (reprint author), Duke Univ, Med Ctr, 047 Baker House,Trent Dr,DUMC Box 3624, Durham, NC 27710 USA. EM fried003@mc.duke.edu RI leng, xianwei/F-9073-2011 NR 29 TC 1105 Z9 1120 U1 6 U2 67 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2009 VL 27 IS 28 BP 4733 EP 4740 DI 10.1200/JCO.2008.19.8721 PG 8 WC Oncology SC Oncology GA 500LS UT WOS:000270304100017 PM 19720927 ER PT J AU DiPersio, JF Micallef, IN Stiff, PJ Bolwell, BJ Maziarz, RT Jacobsen, E Nademanee, A McCarty, J Bridger, G Calandra, G AF DiPersio, John F. Micallef, Ivana N. Stiff, Patrick J. Bolwell, Brian J. Maziarz, Richard T. Jacobsen, Eric Nademanee, Auayporn McCarty, John Bridger, Gary Calandra, Gary TI Phase III Prospective Randomized Double-Blind Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared With Placebo Plus Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients With Non-Hodgkin's Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; CXCR4 ANTAGONIST AMD3100; DOSE G-CSF; CHEMOKINE RECEPTOR; RAPID MOBILIZATION; POOR MOBILIZATION; ELIGIBLE PATIENTS; MULTIPLE-MYELOMA; CHEMOTHERAPY; DISEASE AB Purpose This study evaluates the safety and efficacy of plerixafor (AMD3100), a CXCR4 antagonist, in mobilizing hematopoietic stem cells for autologous stem-cell transplantation in non-Hodgkin's lymphoma (NHL) patients. Patients and Methods This is a phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study. Patients with non-Hodgkin's lymphoma requiring an autologous hematopoietic stem-cell transplantation in first or second complete or partial remission were eligible. Patients received granulocyte colony-stimulating factor (G-CSF; 10 mu g/kg) subcutaneously daily for up to 8 days. Beginning on evening of day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 mu g/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until >= 5 X 10(6)C D34+ cells/kg were collected. The primary end point was the percentage of patients who collected >= 5 X 10(6) CD34+ cells/kg in 4 or fewer apheresis days. Results This report presents all data for all patients (n = 298) through 12 months follow-up. Eighty-nine (59%) of 150 patients in the plerixafor group and 29 (20%) of 148 patients in the placebo group met the primary end point (P < .001). One hundred thirty-five patients (90%) in plerixafor group and 82 patients (55%) in placebo group underwent transplantation after initial mobilization. Median time to engraftment was similar in both groups. The most common plerixafor-associated adverse events were GI disorders and injection site reactions. Conclusion Plerixafor and G-CSF were well tolerated and resulted in a significantly higher proportion of patients with non-Hodgkin's lymphoma achieving the optimal CD34(+) cell target for transplantation in fewer apheresis days, compared with G-CSF alone. C1 [DiPersio, John F.] Washington Univ, Sch Med, Div Oncol, Siteman Canc Ctr, St Louis, MO 63130 USA. Mayo Clin, Rochester, MN USA. Loyola Univ, Maywood, IL 60153 USA. Cleveland Clin, Cleveland, OH 44106 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genzyme Corp, Cambridge, MA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Virginia Commonwealth Univ, Richmond, VA USA. RP DiPersio, JF (reprint author), Washington Univ, Sch Med, Div Oncol, Siteman Canc Ctr, St Louis, MO 63130 USA. EM jdipersi@im.wustl.edu NR 33 TC 326 Z9 331 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2009 VL 27 IS 28 BP 4767 EP 4773 DI 10.1200/JCO.2008.20.7209 PG 7 WC Oncology SC Oncology GA 500LS UT WOS:000270304100022 PM 19720922 ER PT J AU Kane, JM Correll, CU Goff, DC Kirkpatrick, B Marder, SR Vester-Blokland, E Sun, W Carson, WH Pikalov, A Assuncao-Talbott, S AF Kane, John M. Correll, Christoph U. Goff, Donald C. Kirkpatrick, Brian Marder, Stephen R. Vester-Blokland, Estelle Sun, Wei Carson, William H. Pikalov, Andrei Assuncao-Talbott, Sheila TI A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of Adjunctive Aripiprazole for Schizophrenia or Schizoaffective Disorder Inadequately Treated With Quetiapine or Risperidone Monotherapy SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BROAD EFFECTIVENESS TRIAL; REFRACTORY SCHIZOPHRENIA; PARTIAL AGONIST; OPEN-LABEL; ATYPICAL ANTIPSYCHOTICS; CLOZAPINE COMBINATION; PSYCHIATRIC PRACTICE; RATING-SCALE; AUGMENTATION; RELIABILITY AB Objective: Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder. Method: In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score. Results: 323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P=.942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (- 12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (- 18.7 ng/mL vs - 1.9 ng/mL; P < .001) but not in the quetiapine subgroup (- 3.01 ng/mL vs + 0.15 ng/mL; P = .104). Conclusions: The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia. Trial Registration: clinicaltrials.gov Identifier: NCT00325689 J Clin Psychiatry 2009;70(10):1348-1357 (C) Copyright 2009 Physicians Postgraduate Press, Inc. C1 [Kane, John M.; Correll, Christoph U.] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY 11004 USA. [Goff, Donald C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kirkpatrick, Brian] Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. [Marder, Stephen R.] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA. [Vester-Blokland, Estelle] Bristol Myers Squibb Co, Paris, France. [Sun, Wei; Assuncao-Talbott, Sheila] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Carson, William H.] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Pikalov, Andrei] Otsuka Amer Pharmaceut Inc, Rockville, MD USA. RP Kane, JM (reprint author), Zucker Hillside Hosp, Dept Psychiat, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM psychiatry@lij.edu RI Correll, Christoph/D-3530-2011 FU NIMH NIH HHS [K24 MH002025] NR 52 TC 57 Z9 62 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2009 VL 70 IS 10 BP 1348 EP 1357 DI 10.4088/JCP.09m05154yel PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 511LH UT WOS:000271166100002 PM 19906340 ER PT J AU Lundstrom, BN Famulare, M Sorensen, LB Spain, WJ Fairhall, AL AF Lundstrom, Brian Nils Famulare, Michael Sorensen, Larry B. Spain, William J. Fairhall, Adrienne L. TI Sensitivity of firing rate to input fluctuations depends on time scale separation between fast and slow variables in single neurons SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Noise; Gain; f-I curve; Stimulus fluctuations; Single neuron; Time scales; Dynamical systems; Phase portrait; Hodgkin-Huxley; Slow adaptation; Slow AHP ID NEOCORTICAL NEURONS; IN-VIVO; GAIN MODULATION; NEURAL CODE; CONDUCTANCE; ADAPTATION; NOISE; OSCILLATIONS; DYNAMICS; DETECTOR AB Neuronal responses are often characterized by the firing rate as a function of the stimulus mean, or the f-I curve. We introduce a novel classification of neurons into Types A, B-, and B+ according to how f-I curves are modulated by input fluctuations. In Type A neurons, the f-I curves display little sensitivity to input fluctuations when the mean current is large. In contrast, Type B neurons display sensitivity to fluctuations throughout the entire range of input means. Type B- neurons do not fire repetitively for any constant input, whereas Type B+ neurons do. We show that Type B+ behavior results from a separation of time scales between a slow and fast variable. A voltage-dependent time constant for the recovery variable can facilitate sensitivity to input fluctuations. Type B+ firing rates can be approximated using a simple "energy barrier" model. C1 [Lundstrom, Brian Nils; Spain, William J.; Fairhall, Adrienne L.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Famulare, Michael; Sorensen, Larry B.] Univ Washington, Dept Phys, Seattle, WA 98195 USA. [Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Neurol Sect, Seattle, WA 98108 USA. RP Lundstrom, BN (reprint author), Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. EM lundbr@u.washington.edu FU Burroughs-Wellcome Careers at the Scientific Interface; McKnight Scholar Award; National Institute of Neurological Disorders and Stroke [F30NS055650]; Medical Scientist Training Program; National Institute of General Medical Sciences; ARCS fellowship; VA Merit Review FX This work was supported by a Burroughs-Wellcome Careers at the Scientific Interface grant and a McKnight Scholar Award; BNL was supported by grant number F30NS055650 from the National Institute of Neurological Disorders and Stroke, the Medical Scientist Training Program at UW supported by the National Institute of General Medical Sciences, and an ARCS fellowship; WJS was supported by a VA Merit Review. NR 40 TC 28 Z9 28 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD OCT PY 2009 VL 27 IS 2 BP 277 EP 290 DI 10.1007/s10827-009-0142-x PG 14 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 488AG UT WOS:000269320300008 PM 19353260 ER PT J AU Mandal, RV Duncan, LM Austen, WG Nielsen, GP AF Mandal, Rajni V. Duncan, Lyn M. Austen, William G., Jr. Nielsen, G. Petur TI Infiltrating intramuscular spindle cell lipoma of the face SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID LIPOSARCOMA; VARIANT; FEATURES; TUMORS; SKIN AB Mandal RV, Duncan LM, Austen WG, Nielsen GP. Infiltrating intramuscular spindle cell lipoma of the face. C1 [Mandal, Rajni V.; Duncan, Lyn M.; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Austen, William G., Jr.] Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Mandal, RV (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM rmandal@partners.org NR 31 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 2009 VL 36 BP 70 EP 73 DI 10.1111/j.1600-0560.2008.01219.x PG 4 WC Dermatology; Pathology SC Dermatology; Pathology GA 496LT UT WOS:000269976300016 PM 19187113 ER PT J AU Kasivisvanathan, V Levine, A Kasivisvanathan, R Brown, DFM Nadel, ES AF Kasivisvanathan, Veeru Levine, Adam Kasivisvanathan, Ramanathan Brown, David F. M. Nadel, Eric S. TI DYSPNEA AND MULTIPLE PULMONARY NODULES SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID STAPHYLOCOCCUS-AUREUS ENDOCARDITIS; INFECTIVE ENDOCARDITIS; ANTIBIOTIC-TREATMENT; MEDICAL PROGRESS; DIAGNOSIS; GUIDELINES; DISEASE C1 [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Kasivisvanathan, Veeru] Univ London Imperial Coll Sci Technol & Med, London, England. [Kasivisvanathan, Veeru; Levine, Adam; Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kasivisvanathan, Ramanathan] Univ Coll Hosp, Dept Anesthesia & Intens Care, London, England. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2009 VL 37 IS 3 BP 300 EP 304 PG 5 WC Emergency Medicine SC Emergency Medicine GA 502DL UT WOS:000270435000011 PM 19717265 ER PT J AU Giles, KA Hamdan, AD Pomposelli, FB Wyers, MC Dahlberg, SE Schermerhorn, ML AF Giles, Kristina A. Hamdan, Allen D. Pomposelli, Frank B. Wyers, Mark C. Dahlberg, Suzanne E. Schermerhorn, Marc L. TI Population-Based Outcomes Following Endovascular and Open Repair of Ruptured Abdominal Aortic Aneurysms SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE abdominal aortic aneurysm; ruptured aneurysm; endovascular aneurysm repair; open surgery; mortality; outcome analysis; population-based outcomes ID RANDOMIZED CONTROLLED-TRIAL; INTENTION-TO-TREAT; METAANALYSIS; IMPACT; EVAR; FEASIBILITY; MORTALITY; SURGERY; VOLUME AB Purpose: To evaluate national outcomes after endovascular and open surgical repair of ruptured abdominal aortic aneurysms (rAAA). Methods: The Nationwide Inpatient Sample was interrogated to identify all repairs between 2000 and 2005 for rAAA based on ICD-9 codes. In the study period, 2323 patients (1794 men; median age 75 years, range 45-98) with rAAAs had endovascular repair, while 26,106 patients (20,311 men; median age 73 years, range 22-99) had an open procedure. Outcomes included in-hospital mortality, length of stay (LOS), complications, and hospitalization charge. A secondary analysis was performed to compare outcomes from low-, medium-, and high-volume institutions based on annual rAAA repair volume. Results: Patients in the endovascular group were significantly older (p<0.05). Mortality was 41% overall: 33% and 41% for endovascular versus open repair, respectively (p<0.001). Mortality after endovascular repair was lower than open surgery for patients >= 70 years (36% versus 47%, p<0.001), but not for those <70 years (24% versus 30%, p=0.15). LOS was shorter after endovascular repair (7 versus 9 days, p<0.001). Respiratory complications (8% versus 4%, p<0.05) and acute renal failure were more common following open repair (30% versus 23%, p<0.01). Costs were similar (endo $73,590 versus open $67,287, p=0.15). Mortality decreased as hospital surgical volume increased (low 44%, medium 39%, high 38%; p<0.001). Over time, endovascular repair utilization increased more rapidly at high-volume centers, and a lower mortality was seen with endovascular repair at high-volume compared to low-volume hospitals (22% versus 44%, p<0.001). Multivariate predictors of mortality were age, female gender, lower hospital surgical volume, open repair, and year of surgery. Conclusion: This population-based study found that mortality associated with rAAAs may be improved by the performance of endovascular repair, especially in older patients. Mortality after rAAA for both endovascular and open repairs was also lower at high-volume institutions. J Endovasc Ther. 2009;16:554-564 C1 [Giles, Kristina A.; Hamdan, Allen D.; Pomposelli, Frank B.; Wyers, Mark C.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02215 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schermerhorn, ML (reprint author), 110 Francis St,Suite 5B, Boston, MA 02215 USA. EM mscherm@bidmc.harvard.edu FU National Institutes of Health (NIH) [HL007734] FX This research was supported by Grant HL007734 (T32 Harvard-Longwood Research Training in Vascular Surgery) from the National Institutes of Health (NIH). In accordance with the NIH Public Access Policy, this article is available for open access at PubMed Central. NR 34 TC 40 Z9 43 U1 0 U2 3 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD OCT PY 2009 VL 16 IS 5 BP 554 EP 564 DI 10.1583/09-2743.1 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 513FV UT WOS:000271308800005 PM 19842719 ER PT J AU Datta, GD Neville, BA Kawachi, I Datta, NS Earle, CC AF Datta, G. Dabral Neville, B. A. Kawachi, I. Datta, N. S. Earle, C. C. TI Marital status and survival following bladder cancer SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID COMORBIDITY INDEX; HEALTH-CARE; MORTALITY; MORBIDITY; MARRIAGE; THERAPY; PROGRESSION; PHYSICIAN; IMPACT; MEN AB Background: Marital status has been implicated as a prognostic factor in bladder cancer survival. However, few studies have explored potential mechanisms through which this might occur. Methods: The study identified 19 982 bladder cancer patients from the SEER-Medicare database (1992-8) and constructed sex-specific Cox proportional hazard models to assess the relation between marital status and 5-year survival, while sequentially adding covariates to test possible mechanisms. Results: Multivariable Cox analyses suggest that at every stage, married men had better survival than unmarried men independent of age, race, ecologic socioeconomic status, comorbidities, any or aggressive treatment (assessed separately), and accessing a teaching hospital (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.74 to 0.87). Among women with stages II-IV bladder cancer, age and the presence of comorbid conditions explained the association between marital status and survival. However, among those diagnosed with stage I bladder cancer, none of the covariates explained the association between marital status and decreased mortality (fully adjusted HR 0.72; 95% CI 0.62 to 0.84). Conclusion: The lack of evidence of mediation through treatment, overall health, SES, or quality of healthcare institution among married men and women with stage I disease suggests they may be benefiting from something other than these factors, perhaps practical or social support. C1 [Datta, G. Dabral; Kawachi, I.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Datta, G. Dabral; Kawachi, I.] Harvard Univ, Sch Publ Hlth, Ctr Soc & Hlth, Boston, MA 02115 USA. [Neville, B. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Datta, N. S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Earle, C. C.] Canc Care Ontario, Hlth Serv Res Program, Toronto, ON, Canada. [Earle, C. C.] Ontario Inst Canc Res, Toronto, ON, Canada. RP Datta, GD (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,Kresge Bldg 7th Floor, Boston, MA 02115 USA. EM gdatta@hsph.harvard.edu FU National Cancer Institute [CA 91753-02]; Robert Wood Johnson Foundation; W. K. Kellogg Fellowship in Health Disparities; Alonzo Smythe Yerby Postdoctoral Fellowship FX This project was supported by grants from the National Cancer Institute (CA 91753-02) and the Robert Wood Johnson Foundation. At the time the project was complete Dr G. D. Datta was supported by the W. K. Kellogg Fellowship in Health Disparities and the Alonzo Smythe Yerby Postdoctoral Fellowship. NR 39 TC 18 Z9 18 U1 2 U2 12 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD OCT PY 2009 VL 63 IS 10 BP 807 EP 813 DI 10.1136/jech.2008.082438 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 494CI UT WOS:000269786600008 PM 19468015 ER PT J AU Bennett, DL Hernanz-Schulman, M Nealy, BJ Kan, JH Mencio, GA Damon, B AF Bennett, Debbie Lee Hernanz-Schulman, Marta Nealy, Bobbi J. Kan, J. Herman Mencio, Gregory A. Damon, Bruce TI Buckle fractures in children: Is urgent treatment necessary? SO JOURNAL OF FAMILY PRACTICE LA English DT Article AB Purpose To determine whether the clinical outcome of buckle fractures in children differs between those treated acutely on the same day of trauma and those treated subacutely, and whether a change in practice patterns based on these data would result in cost savings. Methods In this retrospective cohort study-approved by the Institutional Review Board-we reviewed the cases of 341 consecutive patients <18 years of age seen by the pediatric orthopedic clinic for treatment of isolated extremity buckle fractures between July 1, 2004 and August 31, 2007. Time from injury to treatment was used to divide patients into 2 groups: acute (<= 1 day; n=155) and subacute treatment (>1 day; n=186). Clinical outcome at final orthopedic follow-up was recorded for each patient. We defined adverse outcome as fractures requiring manipulation, clinically apparent deformity, or functional impairment. Charge analysis compared differences in management costs for patients with buckle fractures presenting initially to the emergency department (ED) and those seen solely in the orthopedic clinic. Results No adverse outcomes were identified in either acute or subacute treatment groups. Total clinical visits did not vary (acute, 3.2 vs subacute, 3.1; P=.051). Presence of mild angulation of fractures on radiographs did not differ significantly between acute and subacute management groups at initial presentation (6.5% vs 8.6%; P=.541) or at final follow-up (12.2% vs 12.4%; P=1.0). A cost savings of approximately $3000 could have been realized for each patient referred to the ED who might otherwise have been seen subacutely in the orthopedic clinic. Conclusions No adverse clinical outcomes resulted from subacute treatment of stable buckle fractures. Cost and time savings may be realized with subacute management of buckle fractures without affecting clinical outcome. C1 [Bennett, Debbie Lee; Hernanz-Schulman, Marta; Nealy, Bobbi J.; Kan, J. Herman] Vanderbilt Childrens Hosp, Dept Radiol & Radiol Sci, Nashville, TN USA. [Mencio, Gregory A.] Vanderbilt Childrens Hosp, Dept Orthoped Surg, Nashville, TN USA. [Damon, Bruce] Vanderbilt Univ, Dept Radiol & Radiol Sci, Nashville, TN USA. [Damon, Bruce] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN USA. [Damon, Bruce] Vanderbilt Univ, Dept Mol Physiol, Nashville, TN USA. Vanderbilt Univ, Biophys Program Chem & Phys Biol, Nashville, TN USA. RP Bennett, DL (reprint author), Massachusetts Gen Hosp, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM dlbennett@partners.org NR 8 TC 5 Z9 5 U1 0 U2 1 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD OCT PY 2009 VL 58 IS 10 BP E1 EP E6 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA V18HF UT WOS:000207995200001 PM 19874727 ER PT J AU Jandasek, B Holmbeck, GN DeLucia, C Zebracki, K Friedman, D AF Jandasek, Barbara Holmbeck, Grayson N. DeLucia, Christian Zebracki, Kathy Friedman, Deborah TI Trajectories of Family Processes Across the Adolescent Transition in Youth With Spina Bifida SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE spina bifida; family processes; growth curve; adolescence ID PARENT-CHILD CONFLICT; PSYCHOSOCIAL ADJUSTMENT; YOUNG ADOLESCENTS; PREADOLESCENTS; PSYCHOPATHOLOGY; MULTIMETHOD; INFORMANT; AUTONOMY; MODELS; ISSUES AB The current study investigated change in family processes, including conflict, cohesion, and stress, across the adolescent transition, comparing the developmental trajectories of youth with and without spina bifida. Individual growth curve modeling procedures were utilized to describe the developmental course of family processes across 4 waves of data collection, from ages 9 to 15 years, and to test whether illness status (spina bifida vs. matched comparison group [N = 68 for both groups at Time 1]) would significantly predict individual variability in family processes. Potential moderators (child gender, socioeconomic status [SES], and child verbal ability) of the association between illness status and family functioning were also examined. Differences were found between the trajectories of family processes for families of youth with and without spina bifida. For families of youth with spina bifida, changes in family conflict and cohesion may be less dramatic than or inconsistent with what is expected during typical adolescence. Families of youth with spina bifida from low SES homes appear to demonstrate resilience in terms of family stress. C1 [Jandasek, Barbara] Brown Univ, Warren Alpert Med Sch, Bradley Hasbro Childrens Res Ctr, Providence, RI 02912 USA. [Holmbeck, Grayson N.] Loyola Univ, Chicago, IL 60611 USA. [DeLucia, Christian] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Zebracki, Kathy] Shriners Hosp Children, Chicago, IL USA. [Zebracki, Kathy] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL USA. [Friedman, Deborah] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jandasek, B (reprint author), Rhode Isl Hosp, Dept Child & Adolescent Psychiat, Bradley Hasbro Childrens Res Ctr, 1 Hoppin St,Suite 204,Coro W, Providence, RI 02903 USA. EM Barbara_Jandasek@Brown.edu FU NICHD NIH HHS [R01 HD048629, R01 HD048629-05] NR 44 TC 18 Z9 18 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD OCT PY 2009 VL 23 IS 5 BP 726 EP 738 DI 10.1037/a0016116 PG 13 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 506SL UT WOS:000270796200011 PM 19803608 ER PT J AU Choi, KD Kim, N Jang, IJ Park, YS Cho, JY Kim, JR Shin, JM Jung, HC Song, IS AF Choi, Kee Don Kim, Nayoung Jang, In-Jin Park, Young Soo Cho, Joo Youn Kim, Jung-Ryul Shin, Jai Moo Jung, Hyun Chae Song, In Sung TI Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE CYP2C19; Helicobacter pylori; intravenous infusions; peptic ulcer bleeding; proton pump inhibitor ID PROTON-PUMP INHIBITOR; HELICOBACTER-PYLORI INFECTION; INTRAGASTRIC PH; EXTENSIVE METABOLIZERS; ATROPHIC GASTRITIS; GENOTYPE STATUS; OMEPRAZOLE; RABEPRAZOLE; ACID; POLYMORPHISM AB Background and Aim: The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low-dose PPI has a similar efficacy to high-dose i.v. administration for maintaining intragastric pH above 6. Methods: Sixty-one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed. Results: Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (-) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% (P = 0.026). Conclusions: A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6. C1 [Choi, Kee Don; Kim, Nayoung; Park, Young Soo; Jung, Hyun Chae; Song, In Sung] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Choi, Kee Don; Kim, Nayoung; Park, Young Soo; Jung, Hyun Chae; Song, In Sung] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea. [Jang, In-Jin; Cho, Joo Youn; Kim, Jung-Ryul] Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul, South Korea. [Choi, Kee Don] Univ Ulsan, Coll Med, Dept Internal Med, Asan Med Ctr, Ulsan, South Korea. [Kim, Nayoung; Park, Young Soo] Seoul Natl Univ, Dept Internal Med, Bundang Hosp, Seognam, Gyeonggi Do, South Korea. [Shin, Jai Moo] Univ Calif Los Angeles, Dept Physiol & Med, Digest Res Ctr, Los Angeles, CA USA. [Shin, Jai Moo] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Kim, N (reprint author), Seoul Natl Univ, Dept Internal Med, Bundang Hosp, 300 Gumi Dong, Seognam Si 463707, Gyeonggi Do, South Korea. EM nayoungkim49@empal.com RI Kim, Nayoung/J-5387-2012; Cho, Joo-Youn/J-5672-2012; Jung, Hyun Chae/J-5654-2012; Park, Young Soo/J-5491-2012; OI Kim, Nayoung/0000-0002-9397-0406 FU Seoul National University Bundang Hospital Research fund [2006-04-027] FX We appreciate the skillful assistance of Ji Suk Park. This work was supported by grant no. 2006-04-027 from the Seoul National University Bundang Hospital Research fund. NR 32 TC 11 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2009 VL 24 IS 10 BP 1617 EP 1624 DI 10.1111/j.1440-1746.2009.05939.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 499AM UT WOS:000270188800008 PM 19686407 ER PT J AU Worthley, DL Leleu, R Whitehall, V Conlon, M Christophersen, C Belobrajdic, D Mallitt, K Ogino, S Irahara, N Leggett, B Young, G AF Worthley, D. L. Leleu, R. Whitehall, V. Conlon, M. Christophersen, C. Belobrajdic, D. Mallitt, K. Ogino, S. Irahara, N. Leggett, B. Young, G. TI A human, double-blind, placebo-controlled, cross-over trial of prebiotic, probiotic and synbiotic supplementation: effects on luminal, inflammatory, epigenetic and epithelial biomarkers of colorectal cancer SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Worthley, D. L.; Whitehall, V.; Leggett, B.] RBWH Res Fdn, Clin Res Ctr, Brisbane, Qld, Australia. [Worthley, D. L.; Mallitt, K.; Leggett, B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Leleu, R.; Young, G.] Flinders Ctr Canc Prevent & Control, Adelaide, SA, Australia. [Leleu, R.; Conlon, M.; Christophersen, C.; Belobrajdic, D.] CSIRO, Adelaide, SA, Australia. [Ogino, S.; Irahara, N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Christophersen, Claus T/C-5512-2008; Belobrajdic, Damien/B-5741-2011; Leggett, Barbara/D-3579-2011; Whitehall, Vicki/B-6262-2013 OI Christophersen, Claus T/0000-0003-1591-5871; Belobrajdic, Damien/0000-0002-5801-8663; Whitehall, Vicki/0000-0002-8285-2391 NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2009 VL 24 BP A239 EP A239 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 503PU UT WOS:000270551200054 ER PT J AU Worthley, DL Whitehall, VL Bampton, P Prosser, R Simms, L Ogino, S Irahara, N Radford-Smith, G Legget, BA AF Worthley, D. L. Whitehall, V. L. Bampton, P. Prosser, R. Simms, L. Ogino, S. Irahara, N. Radford-Smith, G. Legget, B. A. TI Chronic colitis is associatied with significant hypomethylation of LINE-1 within the colorectal mucosa SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Worthley, D. L.; Whitehall, V. L.; Simms, L.; Radford-Smith, G.; Legget, B. A.] RBWH Res Fdn, Clin Res Ctr, Brisbane, Qld, Australia. [Worthley, D. L.; Whitehall, V. L.; Simms, L.; Radford-Smith, G.; Legget, B. A.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Bampton, P.; Prosser, R.] Flinders Med Ctr, Adelaide, SA, Australia. [Ogino, S.; Irahara, N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Whitehall, Vicki/B-6262-2013 OI Whitehall, Vicki/0000-0002-8285-2391 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2009 VL 24 BP A242 EP A242 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 503PU UT WOS:000270551200061 ER PT J AU Volpp, KG Rosen, AK Rosenbaum, PR Romano, PS Itani, KMF Bellini, L Even-Shoshan, O Cen, LY Wang, YL Halenar, MJ Silber, JH AF Volpp, Kevin G. Rosen, Amy K. Rosenbaum, Paul R. Romano, Patrick S. Itani, Kamal M. F. Bellini, Lisa Even-Shoshan, Orit Cen, Liyi Wang, Yanli Halenar, Michael J. Silber, Jeffrey H. TI Did Duty Hour Reform Lead to Better Outcomes Among the Highest Risk Patients? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medical errors internship and residency; education; medical; graduate; personnel staffing and scheduling; continuity of patient care ID QUALITY-OF-CARE; ADMINISTRATIVE DATA; MEDICARE BENEFICIARIES; COMORBIDITY MEASURES; WORK HOURS; MORTALITY; ICD-9-CM; COMPLICATIONS; REGULATIONS; RESIDENT AB BACKGROUND: Earlier work demonstrated that ACGME duty hour reform did not adversely affect mortality, with slight improvement noted among specific subgroups. OBJECTIVE: To determine whether resident duty hour reform differentially affected the mortality risk of high severity patients or patients who experienced postoperative complications (failure-to-rescue). DESIGN: Observational study using interrupted time series analysis with data from July 1, 2000 - June 30, 2005. Fixed effects logistic regression was used to examine the change in the odds of mortality or failure-to-rescue (FTR) in more versus less teaching-intensive hospitals before and after duty hour reform. PARTICIPANTS: All unique Medicare patients (n = 8,529,595) admitted to short-term acute care non-federal hospitals and all unique VA patients (n = 318,636 patients) with principal diagnoses of acute myocardial infarction, congestive heart failure, gastrointestinal bleeding, stroke or a DRG classification of general, orthopedic or vascular surgery. MEASUREMENTS AND MAIN RESULTS: We measured mortality within 30 days of hospital admission and FTR, measured by death among patients who experienced a surgical complication. The odds of mortality and FTR generally changed at similar rates for higher and lower risk patients in more vs. less teaching intensive hospitals. For example, comparing the mortality risk for the 10% of Medicare patients with highest risk to the other 90% of patients in post-reform year 1 for combined medical an OR of 1.01 [95% CI 0.90, 1.13], for combined surgical an OR of 0.91 [95% CI 0.80, 1.04], and for FTR an OR of 0.94 [95% CI 0.80, 1.09]. Findings were similar in year 2 for both Medicare and VA. The two exceptions were a relative increase in mortality for the highest risk medical (OR 1.63 [95% CI 1.08, 2.46]) and a relative decrease in the high risk surgical patients within VA in post-reform year 1 (OR 0.52 [95% CI 0.29, 0.96]). CONCLUSIONS: ACGME duty hour reform was not associated with any consistent improvements or worsening in mortality or failure-to-rescue rates for high risk medical or surgical patients. C1 [Volpp, Kevin G.; Halenar, Michael J.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Bellini, Lisa; Cen, Liyi; Halenar, Michael J.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Silber, Jeffrey H.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Rosen, Amy K.] Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Rosenbaum, Paul R.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Romano, Patrick S.] Univ Calif Davis, Sch Med, Div Gen Med, Davis, CA 95616 USA. [Romano, Patrick S.] Univ Calif Davis, Sch Med, Ctr Healthcare Policy & Res, Davis, CA 95616 USA. [Itani, Kamal M. F.] VA Boston Hlth Care Syst, Dept Surg, Boston, MA USA. [Even-Shoshan, Orit; Wang, Yanli; Silber, Jeffrey H.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. RP Volpp, KG (reprint author), Vet Adm Hosp, Ctr Hlth Equ Res & Promot, 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu RI Rosenbaum, Paul/H-8687-2012; Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 FU VA HSRD [04.202.1]; NHLBI [R01 HL082637]; National Science Foundation [SES-0646002] FX This work was supported primarily by grant VA HSR&D IIR 04.202.1 and NHLBI R01 HL082637, with additional support from National Science Foundation grant SES-0646002. The sponsors/funders have had no role in the design and conduct of the study; collection, management. analysis, and interpretation of the data: and preparation. review, or approval of the manuscript. Dr. Volpp had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We also thank Yun Teng for her assistance with the analyses. Everyone who contributed significantly to this work has been acknowledged. NR 39 TC 54 Z9 54 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2009 VL 24 IS 10 BP 1149 EP 1155 DI 10.1007/s11606-009-1011-z PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 506YQ UT WOS:000270814700012 PM 19455368 ER PT J AU Niekel, MC Lindenhovius, ALC Watson, JB Vranceanu, AM Ring, D AF Niekel, Maarten C. Lindenhovius, Anneluuk L. C. Watson, Jeffrey B. Vranceanu, Ana-Maria Ring, David TI Correlation of DASH and QuickDASH With Measures of Psychological Distress SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE DASH and QuickDASH; depression; pain; catastrophizing; anxiety ID PAIN CATASTROPHIZING SCALE; PHYSICAL IMPAIRMENT; HAND QUESTIONNAIRE; HEALTH-STATUS; ARM PAIN; DISABILITY; SHOULDER; OUTCOMES; PATIENT; DEPRESSION AB Purpose In an attempt to shorten the questionnaires given to patients in both clinical and research settings, we studied whether the correlation of commonly used psychological measures was comparable for the standard Disabilities of the Arm, Shoulder, and Hand (DASH) and the shorter QuickDASH questionnaires. Methods A cohort of 839 patients with carpal tunnel syndrome, trigger finger, de Quervain's disease, trapeziometacarpal arthrosis, lateral epicondylosis, or a distal radius fracture 2 weeks after surgery, who completed the DASH and I or more measures of psychological distress, was created from 10 databases from previously implemented studies. Correlations of the DASH and the QuickDASH with several measures of psychological factors (Center for Epidemiologic Studies Depression Scale [CES-D], Pain Catastrophizing Scale [PCS], and Pain Anxiety Symptoms Scale [PASS-40]) were calculated in both univariate and multivariable analyses. Results There was a large correlation between the DASH and QuickDASH (r = 0.79; p < .001). QuickDASH scores were significantly higher than DASH scores (p < .001). Correlations of the CES-D, PCS, and PASS-40 with the DASH and QuickDASH ranged from small to medium (range, 0.21-0.31; p < .001). There were no significant differences between correlations of the DASH and the QuickDASH with the psychological factors in the cohort including all patients, nor in subgroups according to diagnosis, gender, and limb dominance. Conclusions The correlations of the DASH and QuickDASH with the CES-D, PCS, and PASS-40 were comparable. Our analysis suggests that a shorter and therefore potentially more practical measure of arm-specific disability can be used in studies that evaluate psychosocial aspects of illness behavior. (J Hand Surg 2009;34A:1499-1505. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Acad Med Ctr Amsterdam, Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 29 TC 34 Z9 34 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2009 VL 34A IS 8 BP 1499 EP 1505 DI 10.1016/j.jhsa.2009.05.016 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 506EU UT WOS:000270757500018 PM 19703733 ER PT J AU Newell, P Toffanin, S Villanueva, A Chiang, DY Minguez, B Cabellos, L Savic, R Hoshida, Y Lim, KH Melgar-Lesmes, P Yea, S Peix, J Deniz, K Fiel, MI Thung, S Alsinet, C Tovar, V Mazzaferro, V Bruix, J Roayaie, S Schwartz, M Friedman, SL Llovet, JM AF Newell, Pippa Toffanin, Sara Villanueva, Augusto Chiang, Derek Y. Minguez, Beatriz Cabellos, Laia Savic, Radoslav Hoshida, Yujin Lim, Kiat Hon Melgar-Lesmes, Pedro Yea, Steven Peix, Judit Deniz, Kemal Fiel, M. Isabel Thung, Swan Alsinet, Clara Tovar, Victoria Mazzaferro, Vincenzo Bruix, Jordi Roayaie, Sasan Schwartz, Myron Friedman, Scott L. Llovet, Josep M. TI Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo SO JOURNAL OF HEPATOLOGY LA English DT Article DE Liver cancer; HCV; Signaling pathway; Molecular therapies; Ras; mTOR ID PROMOTER HYPERMETHYLATION; MOLECULAR CLASSIFICATION; ABERRANT METHYLATION; SIGNALING PATHWAYS; SUPPRESSOR GENES; THYROID-TUMORS; HIGH-FREQUENCY; LUNG-CANCER; RASSF1A; NORE1A AB Background/Aims: The success of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC) has focused interest on the role of Ras signaling in this malignancy. We investigated the molecular alterations of the Ras pathway in HCC and the antineoplastic effects of sorafenib in combination with rapamycin, an inhibitor of mTOR pathway, in experimental models. Methods: Gene expression (qRT-PCR, oligonucleotide microarray), DNA copy number changes (SNP-array), methylation of tumor suppressor genes (methylation specific PCR) and protein activation (immunohistochemistry) were analysed in 351 samples. Anti-tumoral effects of combined therapy, targeting the Ras and mTOR pathways were evaluated in cell lines and HCC xenografts. Results: Different mechanisms accounted for Ras pathway activation in HCC. H-ran was up-regulated during different steps of hepatocarcinogenesis. B-raf was overexpressed in advanced tumors and its expression was associated with genomic amplification. Partial methylation of RASSFIA and NOREIA was detected in 89%, and 44%, of tumors respectively, and complete methylation was found in 11 and 4%, of HCCs. Activation of the pathway (PERK immunostaining) was identified in 10.3'% of HCC. Blockade of Ras and mTOR pathways with sorafenib and rapamycin reduced cell proliferation and induced apoptosis in cell lines. In vivo, the combination of both compounds enhanced tumor necrosis and ulceration when compared with sorafenib alone. Conclusions: Ras activation results from several molecular alterations, such as methylation of tumor suppressors and amplification of oncogenes (B-raf). Sorafenib blocks signaling and synergizes with rapamycin in vivo, preventing tumor progression. These data provide the rationale for testing this combination in clinical studies. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain. [Hoshida, Yujin] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Chiang, Derek Y.; Hoshida, Yujin] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Chiang, Derek Y.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chiang, Derek Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Villanueva, Augusto; Peix, Judit; Alsinet, Clara; Tovar, Victoria; Bruix, Jordi; Llovet, Josep M.] Hosp Clin Barcelona, CIBERehd, IDIBAPS, BCLC Grp,HCC Translat Res Lab,Liver Unit, Barcelona, Catalonia, Spain. [Villanueva, Augusto; Peix, Judit; Alsinet, Clara; Tovar, Victoria; Bruix, Jordi; Llovet, Josep M.] Hosp Clin Barcelona, CIBERehd, Dept Pathol, IDIBAPS,BCLC Grp, Barcelona, Catalonia, Spain. [Toffanin, Sara; Mazzaferro, Vincenzo] IRCSS Fdn, Natl Canc Inst, Gastrointestinal Surg & Liver Transplantat Unit, Milan, Italy. [Newell, Pippa; Toffanin, Sara; Minguez, Beatriz; Cabellos, Laia; Savic, Radoslav; Lim, Kiat Hon; Melgar-Lesmes, Pedro; Yea, Steven; Deniz, Kemal; Fiel, M. Isabel; Thung, Swan; Roayaie, Sasan; Schwartz, Myron; Friedman, Scott L.; Llovet, Josep M.] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Div Liver Dis & Hematooncol, New York, NY 10029 USA. [Newell, Pippa; Toffanin, Sara; Minguez, Beatriz; Cabellos, Laia; Savic, Radoslav; Lim, Kiat Hon; Melgar-Lesmes, Pedro; Yea, Steven; Deniz, Kemal; Fiel, M. Isabel; Thung, Swan; Roayaie, Sasan; Schwartz, Myron; Friedman, Scott L.; Llovet, Josep M.] Mt Sinai Sch Med, Dept Med, Mt Sinai Liver Canc Program, New York, NY 10029 USA. [Newell, Pippa; Toffanin, Sara; Minguez, Beatriz; Cabellos, Laia; Savic, Radoslav; Lim, Kiat Hon; Melgar-Lesmes, Pedro; Yea, Steven; Deniz, Kemal; Fiel, M. Isabel; Thung, Swan; Roayaie, Sasan; Schwartz, Myron; Friedman, Scott L.; Llovet, Josep M.] Mt Sinai Sch Med, Div Surg Oncol, Mt Sinai Liver Canc Program, New York, NY 10029 USA. [Newell, Pippa; Toffanin, Sara; Minguez, Beatriz; Cabellos, Laia; Savic, Radoslav; Lim, Kiat Hon; Melgar-Lesmes, Pedro; Yea, Steven; Deniz, Kemal; Fiel, M. Isabel; Thung, Swan; Roayaie, Sasan; Schwartz, Myron; Friedman, Scott L.; Llovet, Josep M.] Mt Sinai Sch Med, Dept Surg, Mt Sinai Liver Canc Program, New York, NY 10029 USA. [Newell, Pippa; Toffanin, Sara; Minguez, Beatriz; Cabellos, Laia; Savic, Radoslav; Lim, Kiat Hon; Melgar-Lesmes, Pedro; Yea, Steven; Deniz, Kemal; Fiel, M. Isabel; Thung, Swan; Roayaie, Sasan; Schwartz, Myron; Friedman, Scott L.; Llovet, Josep M.] Mt Sinai Sch Med, Dept Pathol, Mt Sinai Liver Canc Program, New York, NY 10029 USA. RP Llovet, JM (reprint author), Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Div Liver Dis & Hematooncol, 1425 Madison Ave, New York, NY 10029 USA. EM Josep.Llovet@mssm.edu RI Augusto, Villanueva/F-9378-2012; Minguez, Beatriz/N-4456-2014; Llovet, Josep M /D-4340-2014; Melgar-Lesmes, Pedro/S-3446-2016; Mazzaferro, Vincenzo/C-2726-2017; OI Augusto, Villanueva/0000-0003-3585-3727; Minguez, Beatriz/0000-0002-7276-9666; Llovet, Josep M /0000-0003-0547-2667; Melgar-Lesmes, Pedro/0000-0002-2009-5911; Mazzaferro, Vincenzo/0000-0002-4013-8085; Chiang, Derek/0000-0002-1131-6065; Bruix, Jordi/0000-0002-9826-0753 FU NIH [1RO1 DK37340-23, 1R01DK076986-01]; Associazione Italiana per la Ricerca sul Cancro FX This study was partially supported by a research grant from Bayer Pharmaceuticals to J.M.L. J.B. and J.M.L. are consultants for Bayer Pharmaceuticals. NIH funded study (1RO1 DK37340-23 and 1R01DK076986-01). NR 36 TC 121 Z9 128 U1 3 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD OCT PY 2009 VL 51 IS 4 BP 725 EP 733 DI 10.1016/j.jhep.2009.03.028 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 506BV UT WOS:000270749000020 PM 19665249 ER PT J AU Hunt, D AF Hunt, Daniel TI Hospitalists' Path to Becoming the Best Educators in the Hospital SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID CARE; FACULTY C1 Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educ Serv, Boston, MA 02114 USA. RP Hunt, D (reprint author), Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educ Serv, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM dphunt@partners.org NR 13 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2009 VL 4 IS 8 BP 463 EP 465 DI 10.1002/jhm.615 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 518XP UT WOS:000271729600003 PM 19824091 ER PT J AU Bradshaw, EM Raddassi, K Elyaman, W Orban, T Gottlieb, PA Kent, SC Hafler, DA AF Bradshaw, Elizabeth M. Raddassi, Khadir Elyaman, Wassim Orban, Tihamer Gottlieb, Peter A. Kent, Sally C. Hafler, David A. TI Monocytes from Patients with Type 1 Diabetes Spontaneously Secrete Proinflammatory Cytokines Inducing Th17 Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; BLOOD MONONUCLEAR-CELLS; AUTOIMMUNE INFLAMMATION; GENE-EXPRESSION; RECEPTOR (TLR)2; T-CELLS; DIFFERENTIATION; INTERLEUKIN-23; INDUCTION; CHILDREN AB Autoimmune diseases including type 1 diabetes (T1D) are thought to have a Th1/Th17 bias. The underlying mechanisms driving the activation and differentiation of these proinflammatory T cells are unknown. We examined the monocytes isolated directly from the blood of T1D patients and found they spontaneously secreted the proinflammatory cytokines IL-1 beta and IL-6, which are known to induce and expand Th17 cells. Moreover, these in vivo-activated monocytes from T1D subjects induced more IL-17-secreting cells from memory T cells compared with monocytes from healthy control subjects. The induction of IL-17-secreting T cells by monocytes from T1D subjects was reduced in vitro with a combination of an IL-6-blocking Ab and IL-1R antagonist. In this study, we report a significant although modest increase in the frequency of IL-17-secreting cells in lymphocytes from long-term patients with T1D compared with healthy controls. These data suggest that the innate immune system in T1D may drive the adaptive immune system by expanding the Th17 population of effector T cells. The Journal of Immunology, 2009,183: 4432-4439. C1 [Bradshaw, Elizabeth M.; Raddassi, Khadir; Elyaman, Wassim; Kent, Sally C.; Hafler, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Mol Immunol,Ctr Neurol Dis, Boston, MA 02115 USA. [Orban, Tihamer] Harvard Univ, Joslin Diabet Ctr, Sch Med, Sect Immunol & Immunogenet, Boston, MA 02215 USA. [Gottlieb, Peter A.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Denver & Hlth Sci Ctr, Aurora, CO 80045 USA. RP Hafler, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Mol Immunol,Ctr Neurol Dis, NRB 641,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM hafler@broad.mit.edu FU U.S. National Institutes of Health [P01 AI045757, U19 AI046130, U19 AI070352, P01 A1039671, F32 AI651003, F32 NS059205]; Juvenile Diabetes Research Foundation International; National Institute of Neurological Disorders and Stroke [NS2427] FX These studies were supported by grants from the U.S. National Institutes of Health to D.A.H. (P01 AI045757. U19 AI046130. U19 AI070352, and P01 A1039671), E.M.B. (F32 AI651003), and W.E. (F32 NS059205). S.C.K. is supported by grants from the Juvenile Diabetes Research Foundation International. D.A.H. is also supported by a Jacob Javits Merit Award (NS2427) from the National Institute of Neurological Disorders and Stroke. NR 32 TC 116 Z9 121 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2009 VL 183 IS 7 BP 4432 EP 4439 DI 10.4049/jimmunol.0900576 PG 8 WC Immunology SC Immunology GA 503GU UT WOS:000270522500036 PM 19748982 ER PT J AU Nasir, R Ching, M Shen, Y Jeste, S Tan, WH Wu, BL AF Nasir, R. Ching, M. Shen, Y. Jeste, S. Tan, W. -H. Wu, B. -L. TI Deletions of neurexin-1 predispose to a wide spectrum of developmental disorders SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Meeting Abstract DE Comparative genomic hybridization; Neurexin-1 C1 [Nasir, R.; Ching, M.] Childrens Hosp Boston, Div Dev Med, Boston, MA USA. [Nasir, R.; Ching, M.; Shen, Y.; Jeste, S.; Tan, W. -H.; Wu, B. -L.] Harvard Univ, Sch Med, Boston, MA USA. [Shen, Y.; Wu, B. -L.] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Shen, Y.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jeste, S.] Childrens Hosp Boston, Div Neurol, Boston, MA USA. [Tan, W. -H.] Childrens Hosp Boston, Div Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0964-2633 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD OCT PY 2009 VL 53 BP 833 EP 833 PG 1 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 499AO UT WOS:000270189000011 ER PT J AU Chintakuntlawar, AV Chodosh, J AF Chintakuntlawar, Ashish V. Chodosh, James TI Chemokine CXCL1/KC and its Receptor CXCR2 Are Responsible for Neutrophil Chemotaxis in Adenoviral Keratitis SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-2; HUMAN CORNEAL FIBROBLASTS; HERPETIC STROMAL KERATITIS; BONE-MARROW CELLS; EPIDEMIC KERATOCONJUNCTIVITIS; INTERLEUKIN-8 EXPRESSION; CYTOKINE EXPRESSION; INFECTION; RECRUITMENT; MICE AB Epidemic keratoconjunctivitis (EKC), caused by human adenovirus (HAdV), is one of the most common ocular infections and results in corneal inflammation and subepithelial infiltrates. Adenoviral keratitis causes significant morbidity to the patients, and is characterized by infiltration of leukocytes in the corneal stroma, and expression of chemokines. The exact role of these chemokines in adenoviral infection has not been studied due to lack of animal models. Here, we have characterized the role of chemokine CXCL1/KC and receptor CXCR2 in adenoviral keratitis using a novel mouse model. Analysis of chemokine expression, leukocyte infiltration, and development of keratitis was performed by ELISA, flow cytometry, and histopathology, respectively. Deficiency of CXCL1 and CXCR2 resulted in delayed infiltration of neutrophils, but not inflammatory monocytes in HAdV-37 corneal infection. CXCL1(-/-) mice showed decreased expression of CXCL2/MIP-2, but not CCL2/MCP-1. CXCR2(-/-) mice showed increased expression of CXCL1 and CXCL2, but not CCL2. Both CXCL1(-/-) and CXCR2(-/-) mice demonstrated keratitis similar to wild-type mice. In conclusion, both CXCL1 and CXCR2 play an important role in chemokine expression and neutrophil infiltration following adenoviral corneal infection, but have a redundant role in the development of keratitis. C1 [Chintakuntlawar, Ashish V.; Chodosh, James] Dean McGee Eye Inst, Mol Pathogenesis Eye Infect Res Ctr, Oklahoma City, OK USA. [Chintakuntlawar, Ashish V.; Chodosh, James] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. [Chintakuntlawar, Ashish V.; Chodosh, James] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA. [Chodosh, James] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, Howe Lab, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU U.S. Public Health Service [R01 EY13124, P30 EY12190, P20 RR017703]; Research to Prevent Blindness, New York, NY FX This work was supported by U.S. Public Health Service grants R01 EY13124, P30 EY12190, and P20 RR017703, and a Physician-Scientist Merit Award (to J.C.) from Research to Prevent Blindness, New York, NY. Authors would like to thank Dr. S. Lira and Dr. C. Brown for CXCL1-/- and CXCR2-/- mice, respectively, and Mr. Roger Astley, Mr. Mark Dittmar, Ms. Linda Boone, and Ms. Louisa Williams for their technical assistance. NR 57 TC 44 Z9 44 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD OCT PY 2009 VL 29 IS 10 BP 657 EP 666 DI 10.1089/jir.2009.0006 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 500TS UT WOS:000270328600002 PM 19642907 ER PT J AU Cubeddu, RJ Cruz-Gonzalez, I Kiernan, TJ Truong, QA Rosenfield, K Leinbach, RC Cadigan, ME Pomerantsev, EV Palacios, IF AF Cubeddu, Roberto J. Cruz-Gonzalez, Ignacio Kiernan, Thomas J. Truong, Quynh A. Rosenfield, Kenneth Leinbach, Robert C. Cadigan, Mary E. Pomerantsev, Eugene V. Palacios, Igor F. TI ST-Elevation Myocardial Infarction Mortality in a Major Academic Center "On-" versus "Off-"Hours SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article ID IN-HOSPITAL MORTALITY; PRIMARY ANGIOPLASTY; TIME; ADMISSION; WEEKEND; OUTCOMES; IMPACT; CARE AB Background A higher mortality rate for weekend myocardial infarction (MI) admissions has been reported and attributed to the lower availability of primary percutaneous coronary intervention (PCI) during off-hours However the data are conflicting and furthermore inapplicable to hospitals where primary PCI is invariably per formed Methods This study was conducted in a tertiary hospital where primary PCI is routinely performed in all patients with ST-elevation myocardial infarction (STEMI) Patients admitted during on-hours (Mon day through Friday 7 am-7 pm) where compared to off hours patients (including weekends) The primary endpoint of in-hospital mortality cardiogenic shock and recurrent MI was examined A second analysis that excluded STEMI transfers in-hospital mortality and reperfusion times was examined Results Between 2003 and 2007 747 STEMI patients (46% on hours vs 56% off-hours) underwent primary PCI Demographic characteristics were similar between on- and off-hours groups However off hours STEMI admissions had significantly greater in-hospital mortality rates (8% vs 37% p = 0 01) and higher rates of cardiogenic shock (37% vs 24% p = 0 0001) Admission arrival time was an independent predictor of in-hospital mortality (hazard ratio [HR] 3 98 95% confidence interval [CI] 1 10-14 38 p = 0 035) Longer door-to balloon times (DTB) were observed during off hours (134 vs 109 minutes p < 0 0001) even after excluding the transfer population (63 vs 89 minutes p < 0 0001) Conclusion Higher rates of in hospital mortality and cardiogenic shock may be expected in STEMI patients admitted during off-hours even when primary PCI is performed Longer DTB times during off-hours may partially explain our findings Strategies to optimize reperfusion time during off hours including perhaps a 24/7 in house STEMI team may be necessary C1 [Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Med Sch,Div Cardiol, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Med Sch,Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. NR 16 TC 18 Z9 18 U1 0 U2 3 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD OCT PY 2009 VL 21 IS 10 BP 518 EP 523 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 687VU UT WOS:000284807100007 PM 19805838 ER PT J AU Egawa, G Osawa, M Uemura, A Miyachi, Y Nishikawa, SI AF Egawa, Gyohei Osawa, Masatake Uemura, Akiyoshi Miyachi, Yoshiki Nishikawa, Shin-Ichi TI Transient Expression of Ephrin B2 in Perinatal Skin Is Required for Maintenance of Keratinocyte Homeostasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; HAIR FOLLICLE DEVELOPMENT; MULTIPLE ROLES; STEM-CELLS; MORPHOGENESIS; MOUSE; LIGANDS; DIFFERENTIATION; ANGIOGENESIS; MELANOBLASTS AB The formation of functional skin entails multiple key signals that are implicated repeatedly in distinct processes during embryogenesis. Although Eph receptors and their membrane-bound ephrin ligands play a role in a wide variety of embryonic processes, their function in skin development has not been addressed. Here, we show that ephrin B2 is transiently expressed in hair buds during embryogenesis and in dermal mesenchymal cells during the perinatal period. Keratinocyte-specific ephrin B2-targeted mutant mice exhibit no skin phenotype, whereas postnatal systemic ephrin B2 ablation results in the enhancement of keratinocyte proliferation. Although the same treatment results in a defect of vascular remodeling, our analyses showed that the keratinocyte phenotype is not caused by hypoxia due to vascular defects. Interestingly, we found an enhanced expression of IL-1 family molecules, which have been implicated in the regulation of keratinocyte proliferation. On the basis of these observations, we propose that the transient expression of ephrin B2 in perinatal dermal mesenchymal cells plays a role in adjusting the activity of the mesenchymal microenvironment that regulates proliferation of keratinocytes. C1 [Egawa, Gyohei] Kyoto Univ, Dept Dermatol, Sakyo Ku, Kyoto, Japan. [Egawa, Gyohei; Osawa, Masatake; Uemura, Akiyoshi; Nishikawa, Shin-Ichi] RIKEN, Ctr Dev Biol, Lab Stem Cell Biol, Kobe, Hyogo, Japan. [Osawa, Masatake] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Egawa, G (reprint author), Kyoto Univ, Dept Dermatol, Sakyo Ku, 54 Kawahara Cho, Kyoto, Japan. EM gyohei@ak.med.kyoto-u.ac.jp OI Uemura, Akiyoshi/0000-0001-5574-5470 FU Leading Project for Realization of Regenerative Medicine FX We thank Saori Yonetani for producing the transgenic mice, Michael Reth for MerCreMer plasmid, and David J Anderson and Toshio Suda for providing EphrinB2LacZ/+, EphB4LacZ/+, and EphrinB2LoxP/LoxP mice. We are grateful to the Laboratory for Animal Resources and Genetic Engineering in RIKEN CDB for the maintenance of mice. This work was supported by grants from the Leading Project for Realization of Regenerative Medicine to SN. NR 35 TC 16 Z9 16 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2009 VL 129 IS 10 BP 2386 EP 2395 DI 10.1038/jid.2009.105 PG 10 WC Dermatology SC Dermatology GA 498SL UT WOS:000270163300013 PM 19571816 ER PT J AU Rosenbach, M Murrell, DF Bystryn, JC Dulay, S Dick, S Fakharzadeh, S Hall, R Korman, NJ Lin, J Okawa, J Pandya, AG Payne, AS Rose, M Rubenstein, D Woodley, D Vittorio, C Werth, BB Williams, EA Taylor, L Troxel, AB Werth, VP AF Rosenbach, Misha Murrell, Dedee F. Bystryn, Jean-Claude Dulay, Sam Dick, Sarah Fakharzadeh, Steve Hall, Russell Korman, Neil J. Lin, Julie Okawa, Joyce Pandya, Amit G. Payne, Aimee S. Rose, Mathew Rubenstein, David Woodley, David Vittorio, Carmela Werth, Benjamin B. Williams, Erik A. Taylor, Lynne Troxel, Andrea B. Werth, Victoria P. TI Reliability and Convergent Validity of Two Outcome Instruments for Pemphigus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID DISEASE; SEVERITY; SYMPTOMS; IMPACT; AREA AB A major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here, we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument. To assess convergent validity, these tools were also correlated with the Physician's Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 (95% confirdence interval (CI) = 0.61-0.91) for the PDAI and 0.77 (0.63-0.91) for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 (0.17-0.60) for the ABSIS and 0.86 (0.76-0.95) for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 (0.96-1.0) for the PDAI and 0.80 (0.65-0.96) for the ABSIS. The PDAI also correlated more closely with the PGA. We conclude that the PDAI is more reproducible and correlates better with physician impression of extent. Subset analysis suggests that for this population of mild-to-moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS. C1 [Rosenbach, Misha; Dulay, Sam; Dick, Sarah; Fakharzadeh, Steve; Lin, Julie; Okawa, Joyce; Payne, Aimee S.; Rose, Mathew; Vittorio, Carmela; Werth, Benjamin B.; Williams, Erik A.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19119 USA. [Murrell, Dedee F.] Univ NSW, Dept Dermatol, St George Hosp, Sydney, NSW, Australia. [Bystryn, Jean-Claude] NYU, Med Ctr, Dept Dermatol, New York, NY 10016 USA. [Hall, Russell] Duke Med Ctr, Dept Dermatol, Div Dermatol, Durham, NC USA. [Korman, Neil J.] Univ Hosp Cleveland, Dept Dermatol, Case Western Med Ctr, Cleveland, OH 44106 USA. [Pandya, Amit G.] Univ Texas SW Med Ctr Dallas, Div Dermatol, Dept Dermatol, Dallas, TX 75390 USA. [Rubenstein, David] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA. [Woodley, David] Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA 90033 USA. [Taylor, Lynne; Troxel, Andrea B.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19119 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Rhodes Pavil,3600 Spruce St, Philadelphia, PA 19119 USA. EM werth@mail.med.upenn.edu OI Troxel, Andrea/0000-0002-1393-3075 FU International Pemphigus and Pemphigoid Foundation; National Institutes of Health [NIH K24-AR 02207] FX This study was supported by a grant to VPW from the International Pemphigus and Pemphigoid Foundation. We acknowledge specific assistance from Janet Segall, William J. Zrnchik II, John Frew, and David Sirois, and the National Institutes of Health to VPW (NIH K24-AR 02207). This work was presented at the Society of Investigative Dermatology in May 2008, and was published in abstract form in the Journal of Investigative Dermatology (abstract) 43: S75, 2008. NR 11 TC 73 Z9 77 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2009 VL 129 IS 10 BP 2404 EP 2410 DI 10.1038/jid.2009.72 PG 7 WC Dermatology SC Dermatology GA 498SL UT WOS:000270163300015 PM 19357707 ER PT J AU Reynoso, ED Turley, SJ AF Reynoso, Erika D. Turley, Shannon J. TI Unconventional antigen-presenting cells in the induction of peripheral CD8(+) T cell tolerance SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE lymph nodes; stroma; parenchymal cell; nonhematopoietic cell ID SINUSOIDAL-ENDOTHELIAL-CELLS; FIBROBLASTIC RETICULAR CELLS; RESTING DENDRITIC CELLS; HEPATIC OVAL CELLS; LYMPH-NODE STROMA; BONE-MARROW; CROSS-PRESENTATION; IN-VIVO; DIFFERENTIAL EXPRESSION; NEGATIVE SELECTION AB Bone marrow-derived APCs are considered the predominant cell type involved in the induction and maintenance of T cell tolerance in vivo. In the periphery, cross-presentation of self-antigens by DCs, in particular, CD8 alpha(+) DCs, has been the most discussed mechanism underlying the induction of CD8(+) T cell tolerance against self. However, nonhematopoietic APCs in the liver, skin, parenchymal tissues, and lymph nodes can also present self-and exogenous antigens to CD8(+) T cells under steady-state conditions. Although far surpassed by their DC counterparts in their ability to stimulate T cell responses, these unconventional APCs have been shown to play a role in the induction, maintenance, and regulation of peripheral CD8(+) T cell tolerance by a multitude of mechanisms. In this review, we will discuss the different nonhematopoietic cells that have been shown to present tissue-specific or exogenous antigens to naive CD8(+) T cells, thereby contributing to the regulation of T cell responses in the periphery. J. Leukoc. Biol. 86: 795-801; 2009. C1 [Reynoso, Erika D.; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Reynoso, Erika D.] Harvard Univ, Sch Med, Dept Med Sci, Boston, MA USA. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu NR 83 TC 9 Z9 9 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 2009 VL 86 IS 4 BP 795 EP 801 DI 10.1189/jlb.0509362 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 501FS UT WOS:000270366500007 PM 19652027 ER PT J AU Gee, RE Shacter, HE Long, JA AF Gee, Rebekah E. Shacter, Hannah E. Long, Judith A. TI Coverage of the Human Papillomavirus Vaccine by US and Canadian Medical Schools SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE human papilloma virus; HPV vaccine; student health; hepatitis B vaccine AB Objective. This study evaluates the degree to which medical school health insurance covers the costs of the human papillomavirus (HPV) vaccine for medical students in the United States and in Canada. Methods. A telephone survey was conducted in November 2007 of every accredited medical school in the United States and in Canada. Results. Thirty-one percent of schools fully covered the vaccine, 18% partially covered it, and the majority, 51%, provided no coverage. In the United States, the Northeast had the highest level of full coverage (61%). In the adjusted model, regional differences were no longer significant. However, private schools (odds ratio [OR] = 4.7; 95% confidence interval [CI] = 1.5-15.3)] and those that covered the hepatitis B vaccine (OR = 19.4; 95% CI = 5.5-68.6) remained more likely to cover the HPV vaccine. For medical schools that provided no HPV vaccine coverage, the average out-of-pocket cost for students was $434. Conclusions. This study shows that most medical students are not being offered health insurance coverage for the HPV vaccine, but that the vaccine was adopted relatively quickly into the armamentarium of medical student health centers. C1 [Gee, Rebekah E.] Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA USA. [Gee, Rebekah E.; Long, Judith A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Shacter, Hannah E.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Long, Judith A.] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA. [Long, Judith A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Gee, RE (reprint author), 423 Guardian Dr,13th Floor Blockley Hall, Philadelphia, PA 19104 USA. EM rebekahgeemd@gmail.com FU Robert Wood Johnson Clinical Scholars Program FX The authors thank the Robert Wood Johnson Clinical Scholars Program for providing funding for the study. NR 8 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD OCT PY 2009 VL 13 IS 4 BP 207 EP 209 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 507DO UT WOS:000270831600004 ER PT J AU Reeves, RK Gillis, J Wong, FE Johnson, RP AF Reeves, R. K. Gillis, J. Wong, F. E. Johnson, R. P. TI Vaccination with SIVmac239 Delta nef activates CD4+T cells in the absence of CD4+T-cell loss SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Symposium on Non-Human Primate Models for AIDS CY DEC 09-12, 2008 CL San Juan, PR SP Wisconsin Natl Primate Res Ctr, Caribbean Primate Res Ctr, Natl Inst Hlth, Natl Inst Allergies & Infect Dis, Off AIDS Res DE live attenuated SIV; protective immunity; simian immunodeficiency virus; T-cell activation ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; ATTENUATED SIV; GASTROINTESTINAL-TRACT; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; RHESUS MACAQUES; ADULT MACAQUES; HIV-INFECTION; MEMORY AB Background Pathogenic HIV and SIV infections characteristically deplete central memory CD4+ T cells and induce chronic immune activation, but it is controversial whether this also occurs after vaccination with attenuated SIVs and whether depletion or activation of CD4+ T-cell play roles in protection against wild-type virus challenge. Methods Rhesus macaques were vaccinated with SIVmac239 Delta nef and quantitative and phenotypic polychromatic flow cytometry analyses were performed on mononuclear cells from blood, lymph nodes and rectal biopsies. Results Animals vaccinated with SIVmac239 Delta nef demonstrated no loss of CD4+ T cells in any tissue, and in fact CCR5+ and CD28+CD95+ central memory CD4+ T cells were significantly increased. In contrast, CD4+ T-cell numbers and CCR5 expression significantly declined in unvaccinated controls challenged with SIVmac239. Also, intracellular Ki67 increased acutely as much as 3-fold over baseline in all tissues after SIVmac239 Delta nef vaccination then declined following primary infection. Conclusion We demonstrated in this study that SIVmac239 Delta nef vaccination did not deplete CD4+ T cells but transiently activated and expanded the memory cell population. However, increases in numbers and activation of memory CD4+ T cells did not appear to influence protective immunity. C1 [Reeves, R. K.; Gillis, J.; Wong, F. E.; Johnson, R. P.] Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA. [Johnson, R. P.] Massachusetts Gen Hosp, Infect Dis Unit, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu FU NCRR NIH HHS [P51 RR00168, P51 RR000168, P51 RR000168-370038]; NIAID NIH HHS [P01 AI071306-01A1, R01 AI062412, R01 AI062412-05, P01 AI071306, U19AI067854-04] NR 34 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2009 VL 38 BP 8 EP 16 DI 10.1111/j.1600-0684.2009.00370.x PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 508BJ UT WOS:000270901500003 PM 19863673 ER PT J AU Maguen, S Metzler, TJ McCaslin, SE Inslicht, SS Henn-Haase, C Neylan, TC Marmar, CR AF Maguen, Shira Metzler, Thomas J. McCaslin, Shannon E. Inslicht, Sabra S. Henn-Haase, Clare Neylan, Thomas C. Marmar, Charles R. TI Routine Work Environment Stress and PTSD Symptoms in Police Officers SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Work environment; traumatic stress; police officers ID EMERGENCY SERVICES PERSONNEL; MALE VIETNAM VETERANS; WAR-ZONE STRESSORS; MENTAL-HEALTH; PSYCHOLOGICAL STRESS; CHILDHOOD TRAUMA; RISK-FACTORS; DISORDER; FEMALE; IMPACT AB This study examined the relationship between routine work environment stress and posttraumatic stress disorder (PTSD) symptoms in a sample of police officers (N = 180) who were first assessed during academy training and reassessed I-year later. In a model that included gender, ethnicity, traumatic exposure prior to entering the academy, current negative life events, and critical incident exposure over the last year, routine work environment stress was most strongly associated with PTSD symptoms. We also found that routine work environment stress mediated the relationship between critical incident exposure and PTSD symptoms and between current negative life events and PTSD symptoms. Ensuring that the work environment is functioning optimally protects against the effects of duty-related critical incidents and negative life events outside police service. C1 [Maguen, Shira; Metzler, Thomas J.; McCaslin, Shannon E.; Inslicht, Sabra S.; Henn-Haase, Clare; Neylan, Thomas C.; Marmar, Charles R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Maguen, Shira; Metzler, Thomas J.; McCaslin, Shannon E.; Inslicht, Sabra S.; Henn-Haase, Clare; Neylan, Thomas C.; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program 116-P,4150 Clement St, San Francisco, CA USA. EM Shira.Maguen@va.gov FU NIMH NIH HHS [R01 MH056350] NR 38 TC 27 Z9 27 U1 0 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2009 VL 197 IS 10 BP 754 EP 760 DI 10.1097/NMD.0b013e3181b975f8 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 507CZ UT WOS:000270829900007 PM 19829204 ER PT J AU Danzer, KM Krebs, SK Wolff, M Birk, G Hengerer, B AF Danzer, Karin M. Krebs, Simon K. Wolff, Michael Birk, Gerald Hengerer, Bastian TI Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE alpha-synuclein; neurodegeneration; oligomers; Parkinson's disease; seeding; aggregation ID SPORADIC PARKINSONS-DISEASE; LEWY BODIES; PROTEIN; AGGREGATION; MEMBRANE; PATHOGENESIS; HYPOTHESIS; ALZHEIMERS; FEATURES; NEURONS AB Lewy bodies, alpha-synuclein (alpha-syn) immunopositive intracellular deposits, are the pathological hallmark of Parkinson's disease (PD). Interestingly, Lewybody-like structures have been identified in fetal tissue grafts about one decade after transplantation into the striatum of PD patients. One possible explanation for the accelerated deposition of alpha-syn in the graft is that the aggregation of alpha-syn from the host tissue to the graft is spread by a prion disease-like mechanism. We discuss here an in vitro model which might recapitulate some aspects of disease propagation in PD. We found here that in vitro-generated alpha-syn oligomers induce transmembrane seeding of alpha-syn aggregation in a dose- and time-dependent manner. This effect was observed in primary neuronal cultures as well as in neuronal cell lines. The seeding oligomers were characterized by a distinctive lithium dodecyl sulfate-stable oligomer pattern and could be generated in a dynamic process out of pore-forming oligomers. We propose that alpha-syn oligomers form as a dynamic mixture of oligomer types with different properties and that alpha-syn oligomers can be converted into different types depending on the brain milieu conditions. Our data indicate that extracellular alpha-syn oligomers can induce intracellular alpha-syn aggregation, therefore we hypothesize that a similar mechanism might lead to alpha-syn pathology propagation. C1 [Danzer, Karin M.; Krebs, Simon K.; Hengerer, Bastian] CNS Res Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. [Wolff, Michael] Boehringer Ingelheim Pharma GmbH & Co KG, Dept Lead Discovery, Biberach, Germany. [Birk, Gerald] Boehringer Ingelheim Pharma GmbH & Co KG, Genom Grp, Biberach, Germany. RP Danzer, KM (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM kdanzer@partners.org NR 40 TC 115 Z9 115 U1 1 U2 19 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2009 VL 111 IS 1 BP 192 EP 203 DI 10.1111/j.1471-4159.2009.06324.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 494JC UT WOS:000269807900019 PM 19686384 ER PT J AU Stoothoff, W Jones, PB Spires-Jones, TL Joyner, D Chhabra, E Bercury, K Fan, ZY Xie, H Bacskai, B Edd, J Irimia, D Hyman, BT AF Stoothoff, Will Jones, Phillip B. Spires-Jones, Tara L. Joyner, Daniel Chhabra, Ekta Bercury, Kathryn Fan, Zhanyun Xie, Hong Bacskai, Brian Edd, Jon Irimia, Daniel Hyman, Bradley T. TI Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; axonal transport; mitochondria; tau; tauopathy ID ALZHEIMERS-DISEASE; MOUSE MODEL; NEUROFIBRILLARY TANGLES; FRONTOTEMPORAL DEMENTIA; OXIDATIVE STRESS; PROTEIN; EXPRESSION; KINESIN; VESICLES; NEURONS AB Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau over-expression diminishes axonal transport in several systems, but differential effects of 3 repeat and 4 repeat isoforms have not been studied. We examined the effects of tau on mitochondrial transport and found that both 3 repeat and 4 repeat tau change normal mitochondrial distribution within the cell body and reduce mitochondrial localization to axons; 4 repeat tau has a greater effect than 3 repeat tau. Further, we observed that the 3 repeat and 4 repeat tau cause different alterations in retrograde and anterograde transport dynamics with 3 repeat tau having a slightly stronger effect on axon transport dynamics. Our results indicate that tau-induced changes in axonal transport may be an underlying theme in neurodegenerative diseases associated with isoform specific changes in tau's interaction with microtubules. C1 [Hyman, Bradley T.] Harvard Univ, Dept Neurol, Alzheimer Dis Res Unit,Med Sch, MassGen Inst Neurodegenerat Dis,Massachusetts Gen, Charlestown, MA 02129 USA. [Stoothoff, Will] Univ Massachusetts, Sch Med, Worcester, MA USA. [Bercury, Kathryn] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Edd, Jon; Irimia, Daniel] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA USA. RP Hyman, BT (reprint author), Harvard Univ, Dept Neurol, Alzheimer Dis Res Unit,Med Sch, MassGen Inst Neurodegenerat Dis,Massachusetts Gen, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Jones, Phillip/0000-0003-0525-6323; Irimia, Daniel/0000-0001-7347-2082 FU [2P50 AG05134]; [1 R01 AG 026249]; [EB00768] FX Supported by 2P50 AG05134, 1 R01 AG 026249 and EB00768. We thank Dr. Larry Goldstein, Dr. Thomas Schwarz, and Dr. Xinnan Wang for advice on kymograph generation and analysis. NR 33 TC 68 Z9 69 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2009 VL 111 IS 2 BP 417 EP 427 DI 10.1111/j.1471-4159.2009.06316.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 498OY UT WOS:000270152600012 PM 19686388 ER PT J AU Rudinskiy, N Kaneko, YA Beesen, AA Gokce, O Regulier, E Deglon, N Luthi-Carter, R AF Rudinskiy, Nikita Kaneko, Yoshio A. Beesen, Ayshe Ana Gokce, Ozgun Regulier, Etienne Deglon, Nicole Luthi-Carter, Ruth TI Diminished hippocalcin expression in Huntington's disease brain does not account for increased striatal neuron vulnerability as assessed in primary neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 3-nitropropionic acid; calcium; excitotoxicity; hippocalcin; huntingtin; Huntington's disease ID CALCIUM SENSOR PROTEINS; RECEPTOR KINASE SUBTYPES; MUTANT HUNTINGTIN; GENE-EXPRESSION; SLOW AFTERHYPERPOLARIZATION; BINDING PROTEIN; MOUSE MODEL; DYSREGULATION; SENSITIVITY; INTERACTS AB Hippocalcin is a neuronal calcium sensor protein previously implicated in regulating neuronal viability and plasticity. Hippocalcin is the most highly expressed neuronal calcium sensor in the medium spiny striatal output neurons that degenerate selectively in Huntington's disease (HD). We have previously shown that decreased hippocalcin expression occurs in parallel with the onset of disease phenotype in mouse models of HD. Here we show by in situ hybridization histochemistry that hippocalcin RNA is also diminished by 63% in human HD brain. These findings lead us to hypothesize that diminished hippocalcin expression might contribute to striatal neurodegeneration in HD. We tested this hypothesis by assessing whether restoration of hippocalcin expression would decrease striatal neurodegeneration in cellular models of HD comprising primary striatal neurons exposed to mutant huntingtin, the mitochondrial toxin 3-nitropropionic acid or an excitotoxic concentration of glutamate. Counter to our hypothesis, hippocalcin expression did not improve the survival of striatal neurons under these conditions. Likewise, expression of hippocalcin together with interactor proteins including the neuronal apoptosis inhibitory protein did not increase the survival of striatal cells in cellular models of HD. These results indicate that diminished hippocalcin expression does not contribute to HD-related neurodegeneration. C1 [Rudinskiy, Nikita; Gokce, Ozgun; Regulier, Etienne; Luthi-Carter, Ruth] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. [Kaneko, Yoshio A.; Beesen, Ayshe Ana] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Deglon, Nicole] MIRCen, CEA, Fontenay Aux Roses, France. [Deglon, Nicole] CEA, CNRS, URA2210, Fontenay Aux Roses, France. RP Luthi-Carter, R (reprint author), Ecole Polytech Fed Lausanne, Brain Mind Inst, Stn 15, CH-1015 Lausanne, Switzerland. EM ruth.luthi-carter@epfl.ch OI gokce, ozgun/0000-0001-6319-404X; Deglon, Nicole/0000-0003-4475-9476 FU Swiss National Science Foundation; EPFL FX We are grateful for the financial support from the Swiss National Science Foundation and the EPFL. We also thank Anne B. Young for sharing laboratory resources, Maria de Fatima Rey for the production of lentiviral vectors, Meredith Dixon, Maria de Fatima Rey and Marc Forrest for production and maintenance of cell cultures, Patrick Schorderet for assistance in cloning cDNAs encoding hippocalcin interactors, Marc Moniatte and Diego Chiappe for mass-spectrometric analysis and Floyd J.-C. Sarria for assistance with image processing. NR 46 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2009 VL 111 IS 2 BP 460 EP 472 DI 10.1111/j.1471-4159.2009.06344.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 498OY UT WOS:000270152600016 PM 19686238 ER PT J AU Gabeau-Lacet, D Engler, D Gupta, S Scangas, GA Betensky, RA Barker, FG Loeffler, JS Louis, DN Mohapatra, G AF Gabeau-Lacet, Darlene Engler, David Gupta, Sumeet Scangas, George A. Betensky, Rebecca A. Barker, Fred G., II Loeffler, Jay S. Louis, David N. Mohapatra, Gayatry TI Genomic Profiling of Atypical Meningiomas Associates Gain of 1q With Poor Clinical Outcome SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Array comparative genomic hybridization; Atypical meningioma ID HIGH-RESOLUTION ANALYSIS; ANAPLASTIC MENINGIOMAS; INTRACRANIAL MENINGIOMA; MALIGNANT MENINGIOMAS; CHROMOSOMAL-ABERRATIONS; HYBRIDIZATION ANALYSIS; SPORADIC MENINGIOMAS; CONSISTENT REGION; GENETIC MODEL; PROGRESSION AB Atypical meningiomas exhibit heterogeneous clinical outcomes. It is unclear which atypical meningiomas require aggressive multimodality treatment with surgery and radiation therapy versus surgery alone to prevent recurrence. Detailed molecular-genetic characterization of these neoplasms is necessary to understand their pathogenesis and identify clinically relevant genetic markers. Oligonucleotide array comparative genomic hybridization was used to identify frequent genetic alterations in 47 primary atypical meningiomas resected at Massachusetts General Hospital between August 1987 and September 2006. Eighty-five percent of samples exhibited loss of 22q, including the neurofibromatosis type 2 gene. The second most frequent regions of loss were confined to the short arm of chromosome 1, particularly 1p33-p36.2 (70%) and 1p13.2 (64%). Other frequent regions of loss, detected in more than 50% of samples, included 14q, 10q, 8q, 7p, 21q, 19, 9q34, and 4p16. Frequent regions of gain were detected along 1q (59%), 17q (44%), 9q34 (30%), and 7q36 (26%). Univariate marker-by-marker analysis of all frequently identified copy number alterations showed potential correlation between gain of 1q and shorter progression-free survival. Given the heterogeneous treatment outcomes of atypical meningioma, investigation of large-scale and focal genomic alterations in multi-institutional efforts may help clarify molecular-genetic signatures of clinical use. C1 [Gabeau-Lacet, Darlene; Scangas, George A.; Louis, David N.; Mohapatra, Gayatry] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gabeau-Lacet, Darlene; Scangas, George A.; Louis, David N.; Mohapatra, Gayatry] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gabeau-Lacet, Darlene; Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gabeau-Lacet, Darlene; Loeffler, Jay S.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Engler, David] Brigham Young Univ, Dept Stat, Provo, UT 84602 USA. [Gupta, Sumeet] Whitehead Inst Biomed Res, Cambridge, England. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Barker, Fred G., II; Louis, David N.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Mohapatra, G (reprint author), Massachusetts Gen Hosp, Dept Pathol, 149 13th St,CNY6016, Charlestown, MA 02129 USA. EM gmohapatra@partners.org FU National Institutes of Health [T32CA09216] FX Darlene Gabeau-Lacet vas supported by Grant No. T32CA09216 from the National Institutes of Health. NR 53 TC 19 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD OCT PY 2009 VL 68 IS 10 BP 1155 EP 1165 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 523EA UT WOS:000272053600011 PM 19918127 ER PT J AU Rader, AA Oman, CM Merfeld, DM AF Rader, A. A. Oman, C. M. Merfeld, D. M. TI Motion Perception During Variable-Radius Swing Motion in Darkness SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID QUALITATIVELY DIFFERENT MECHANISMS; LINEAR ACCELERATION PERCEPTION; HUMAN VESTIBULOOCULAR REFLEX; EYE-MOVEMENT RESPONSES; SPATIAL ORIENTATION; ROLL-TILT; VESTIBULAR PERCEPTION; HUMANS; TRANSLATION; ROTATION AB Rader AA, Oman CM, Merfeld DM. Motion perception during variable-radius swing motion in darkness. J Neurophysiol 102: 2232-2244, 2009. First published July 22, 2009; doi: 10.1152/jn.00116.2009. Using a variable-radius roll swing motion paradigm, we examined the influence of interaural (y-axis) and dorsoventral (z-axis) force modulation on perceived tilt and translation by measuring perception of horizontal translation, roll tilt, and distance from center of rotation (radius) at 0.45 and 0.8 Hz using standard magnitude estimation techniques (primarily verbal reports) in darkness. Results show that motion perception was significantly influenced by both y- and z-axis forces. During constant radius trials, subjects' perceptions of tilt and translation were generally almost veridical. By selectively pairing radius (1.22 and 0.38 m) and frequency (0.45 and 0.8 Hz, respectively), the y-axis acceleration could be tailored in opposition to gravity so that the combined y-axis gravitoinertial force (GIF) variation at the subject's ears was reduced to similar to 0.035 m/s(2) - in effect, the y-axis GIF was "nulled" below putative perceptual threshold levels. With y-axis force nulling, subjects overestimated their tilt angle and underestimated their horizontal translation and radius. For some y-axis nulling trials, a radial linear acceleration at twice the tilt frequency (0.25 m/s(2) at 0.9 Hz, 0.13 m/s(2) at 1.6 Hz) was simultaneously applied to reduce the z-axis force variations caused by centripetal acceleration and by changes in the z-axis component of gravity during tilt. For other trials, the phase of this radial linear acceleration was altered to double the magnitude of the z-axis force variations. z-axis force nulling further increased the perceived tilt angle and further decreased perceived horizontal translation and radius relative to the y-axis nulling trials, while z-axis force doubling had the opposite effect. Subject reports were remarkably geometrically consistent; an observer model-based analysis suggests that perception was influenced by knowledge of swing geometry. C1 [Rader, A. A.; Merfeld, D. M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Res Lab, Boston, MA 02114 USA. [Rader, A. A.; Oman, C. M.] MIT, Man Vehicle Lab, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Rm 421,243 Charles St, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu FU National Aeronautic and Space Administration [NNJ04HF79G]; National Institute of Deafness and Other Communications Disorders [R01 DC-04158] FX Funding for this experiment was generously provided by National Aeronautic and Space Administration Grant NNJ04HF79G and National Institute of Deafness and Other Communications Disorders Grant R01 DC-04158. NR 40 TC 6 Z9 6 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2009 VL 102 IS 4 BP 2232 EP 2244 DI 10.1152/jn.00116.2009 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 508LG UT WOS:000270932000019 PM 19625542 ER PT J AU Liu, HS Buckner, RL Talukdar, T Tanaka, N Madsen, JR Stufflebeam, SM AF Liu, Hesheng Buckner, Randy L. Talukdar, Tanveer Tanaka, Naoaki Madsen, Joseph R. Stufflebeam, Steven M. TI Task-free presurgical mapping using functional magnetic resonance imaging intrinsic activity Laboratory investigation SO JOURNAL OF NEUROSURGERY LA English DT Article DE epilepsy surgery; functional connectivity; neurosurgery; tumor ID RESTING-STATE NETWORKS; MOTOR HAND AREA; ELECTRICAL-STIMULATION; CORTICAL LOCALIZATION; CEREBRAL-CORTEX; WHITE-MATTER; BRAIN-TUMORS; CONNECTIVITY; LANGUAGE; MRI AB Object. Low-frequency components of the spontaneous functional MR imaging signal provide information about the intrinsic functional and anatomical organization of the brain. The ability to use such methods in individual patients may provide a powerful tool for presurgical planning. The authors explore the feasibility of presurgical motor function mapping in which a task-free paradigm is used. Methods. Six surgical candidates with tumors or epileptic foci near the motor cortex participated in this study. The investigators directly compared task-elicited activation of the motor system to activation obtained from intrinsic activity correlations. The motor network within the unhealthy hemisphere was identified based on intrinsic activity correlations, allowing distortions of functional anatomy caused by the tumor and epilepsy to be directly visualized. The precision of the motor function mapping was further explored in 1 participant by using direct cortical stimulation. Results. The motor regions localized based on the spontaneous activity correlations were quite similar to the regions defined by actual movement tasks and cortical stimulation. Using intrinsic activity correlations, it was possible to map the motor cortex in presurgical patients. Conclusions. This task-free paradigm may provide a powerful approach to map functional anatomy in patients without task compliance and allow multiple brain systems to be determined in a single scanning session. (DOI: 10.3171/2008.10.JNS08846) C1 [Liu, Hesheng; Buckner, Randy L.; Talukdar, Tanveer; Tanaka, Naoaki; Stufflebeam, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA 02129 USA. [Buckner, Randy L.; Talukdar, Tanveer] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Stufflebeam, Steven M.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. [Madsen, Joseph R.] Childrens Hosp, Boston, MA 02115 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Stufflebeam, SM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,MIT, Bldg 149,13th St, Charlestown, MA 02129 USA. EM sms@nmr.mgh.harvard.edu OI Liu, Hesheng/0000-0002-7233-1509 FU Howard Hughes Medical Institute; NCRR NIH HHS [P41RR14074]; NIMH NIH HHS [K08 MH067966, K08MH067966] NR 49 TC 45 Z9 50 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 2009 VL 111 IS 4 BP 746 EP 754 DI 10.3171/2008.10.JNS08846 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 503PL UT WOS:000270550000018 PM 19361264 ER PT J AU Liang, HS Liang, P Xu, Y Wu, JN Liang, T Xu, XP AF Liang, Hongsheng Liang, Peng Xu, Ye Wu, Jianing Liang, Tao Xu, Xiaoping TI DHAM-BMSC Matrix Promotes Axonal Regeneration and Functional Recovery after Spinal Cord Injury in Adult Rats SO JOURNAL OF NEUROTRAUMA LA English DT Article DE axonal regeneration; bone marrow stromal cells; denuded human amniotic membrane; spinal cord injury ID MARROW STROMAL CELLS; BONE-MARROW; AMNIOTIC MEMBRANE; EPITHELIAL-CELLS; SCHWANN-CELLS; STEM-CELLS; AUTOLOGOUS TRANSPLANTATION; NEURITE OUTGROWTH; EXPRESSION; REPAIR AB Axonal regeneration and functional recovery after complete spinal cord injury (SCI) are limited in adult mammals. The purpose of this study was to investigate whether an innovative composite matrix made from a denuded human amniotic membrane (DHAM) seeded with bone marrow stromal cells (BMSCs) could promote axonal regeneration after SCI. We transplanted the composite matrix between the stumps of severed spinal cords immediately following SCI. Twelve weeks after surgery, the functional recovery of the hindlimbs of operated rats was evaluated by the Basso-Beattie-Bresnahan (BBB) locomotor rating score and the cold spray test. Axonal regeneration was examined with anterograde and retrograde tracing techniques. Electrophysiological analysis was used to evaluate the improvement in neuronal circuits. Immunohistochemistry was employed to identify local injuries and their recovery. Our results showed that functional recovery was significantly improved in the DHAM-BMSC-transplanted group. Histological studies revealed that host axons grew back into the spinal cord under the composite matrix, and many BMSCs were found in the lesion sites, with some being neurofilament-H (NF-H)-positive, suggesting the possible differentiation of BMSCs into neural-like cells. Furthermore, the restoration of anatomical connections across the injury sites was positively correlated with the recovery of spinal cord conductivity and function in the DHAM-BMSC group. These findings indicate that the DHAM-BMSC composite matrix is a promising therapeutic approach for promoting axonal regeneration and repair SCI. C1 [Liang, Hongsheng; Liang, Peng; Wu, Jianing; Xu, Xiaoping] Harbin Med Coll, Affiliated Hosp 1, Dept Neurosurg, Key Lab Cell Transplantat Minist Hlth China, Harbin 150001, Peoples R China. [Xu, Ye] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Liang, Tao] Harbin Med Coll, Affiliated Hosp 1, Dept Digest, Harbin 150001, Peoples R China. RP Liang, P (reprint author), Harbin Med Coll, Affiliated Hosp 1, Dept Neurosurg, Key Lab Cell Transplantat Minist Hlth China, 23 Youzheng St, Harbin 150001, Peoples R China. EM liangpengd@gmail.com FU National Natural Science Foundation of China [30500517]; Post-graduate Foundation of Harbin Medical University [2007003] FX We thank Dr. Gao Aili, Pan Shangha, and Huang Qi for technical assistance. This study was supported by grants from the National Natural Science Foundation of China ( no. 30500517) and the Post-graduate Foundation of Harbin Medical University ( HCXB No. 2007003). NR 54 TC 8 Z9 9 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2009 VL 26 IS 10 BP 1745 EP 1757 DI 10.1089/neu.2008.0850 PG 13 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 507CT UT WOS:000270829200012 PM 19413502 ER PT J AU Kim, JY Prouty, LA Fang, SC Rodrigues, EG Magari, SR Modest, GA Christiani, DC AF Kim, Jee Young Prouty, Lacey A. Fang, Shona C. Rodrigues, Ema G. Magari, Shannon R. Modest, Geoffrey A. Christiani, David C. TI Association Between Fine Particulate Matter and Oxidative DNA Damage May Be Modified in Individuals With Hypertension SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID AIR-POLLUTION; URINARY 8-HYDROXY-2'-DEOXYGUANOSINE; PERSONAL PARTICULATE; BIOMARKER EVIDENCE; NITRIC-OXIDE; LUNG-CANCER; EXPOSURE; STRESS; PM2.5; PARTICLES AB Objective: To investigate the association between particulate matter (PM(2.5)) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hypertensive and non-hypertensive individuals. Methods: Twelve hypertensives and nine non-hypertensives were monitored during a 36-hour period using a repeated-measures panel study design. Personal exposure to PM(2.5) was assessed using a real-time continuous monitor. Spot urine samples collected at 12-hour intervals were analyzed for 8-OHdG. Results: Exposure to PM(2.5) was associated with a decrease in 8-OHdG in hypertensives compared with an increase in non-hypertensives, after adjusting for age, gender, smoking status, and time of day. Conclusions: The results suggest modification of the association between PM(2.5) exposure and urinary 8-OHdG by hypertension status. Antioxidant activity Present in antihypertensive medications may play a role or PM(2.5) exposure may reduce the capacity to repair DNA damage in hypertensives. These results should be confirmed with further investigation. (J Occup Environ Med. 2009;51:1158-1166) C1 [Kim, Jee Young; Prouty, Lacey A.; Fang, Shona C.; Rodrigues, Ema G.; Magari, Shannon R.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Kim, Jee Young] US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. [Modest, Geoffrey A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Modest, Geoffrey A.] Uphams Corner Hlth Ctr, Dorchester, MA USA. [Christiani, David C.] Harvard Univ, Sch Med, Pulm & Crit Care Unit, Massachusetts Gen Hosp,Dept Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU U.S. EPA STAR [RD-83083801]; NIH [ES00002]; NIEHS [T32 ES007069]; NIOSH [T42 OH008416] FX J.Y.K., S.R.M. and L.A.P. were supported by T32 ES007069 from NIEHS, and S.C.F. was supported by T42 OH008416 from NIOSH. NR 49 TC 10 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 2009 VL 51 IS 10 BP 1158 EP 1166 DI 10.1097/JOM.0b013e3181b967aa PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 506AZ UT WOS:000270746100007 PM 19786898 ER PT J AU Raggio, CL Giampietro, PF Dobrin, S Zhao, C Dorshorst, D Ghebranious, N Weber, JL Blank, RD AF Raggio, Cathleen L. Giampietro, Philip F. Dobrin, Seth Zhao, Chengfeng Dorshorst, Donna Ghebranious, Nader Weber, James L. Blank, Robert D. TI A Novel Locus for Adolescent Idiopathic Scoliosis on Chromosome 12p SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE AIS; axial skeletal growth; chromosome 12p; genetic heterogeneity; susceptibility locus ID LINKAGE ANALYSIS; CURVE PROGRESSION; CANDIDATE REGIONS; SUSCEPTIBILITY; IDENTIFICATION; GENE; DEGRADATION; ASSIGNMENT; SYSTEM; TYPE-1 AB Adolescent idiopathic scoliosis (AIS) is a common disorder with strong evidence for genetic predisposition. Quantitative trait loci (QTLs) for AIS susceptibility have been identified on chromosomes. We performed a genome-wide genetic linkage scan in seven multiplex families using 400 marker loci with a mean spacing of 8.6 cM. We used Genehunter Plus to generate linkage statistics, expressed as homogeneity (HLOD) scores, under dominant and recessive genetic models. We found a significant linkage signal on chromosome 12p, whose support interval extends from near 12pter, spanning approximately 10 million bases or 31 cM. Fine mapping within the region using 20 additional markers reveals maximum HLOD = 3.7 at 5 cM under a dominant inheritance model, and a split peak maximum HLOD = 3.2 at 8 and 18 cM under a recessive inheritance model. The linkage support interval contains 95 known genes. We found evidence suggestive of linkage on chromosomes 1, 6, 7, 8, and 14. This study is the first to find evidence of an AIS susceptibility locus on chromosome 12. Detection of AIS susceptibility OTLs on multiple chromosomes in this and other studies demonstrate that the condition is genetically heterogeneous. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1366-1372, 2009 C1 [Giampietro, Philip F.] Marshfield Clin Fdn Med Res & Educ, Med Genet Serv, Marshfield, WI 54449 USA. [Raggio, Cathleen L.] Hosp Special Surg, Dept Pediat Orthoped, New York, NY 10021 USA. [Giampietro, Philip F.] Univ Wisconsin, Dept Pediat, Madison, WI 53701 USA. [Dobrin, Seth; Zhao, Chengfeng; Dorshorst, Donna; Ghebranious, Nader] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI 54449 USA. [Blank, Robert D.] Univ Wisconsin, Madison, WI 53705 USA. [Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Giampietro, PF (reprint author), Marshfield Clin Fdn Med Res & Educ, Med Genet Serv, 1000 N Oak Ave, Marshfield, WI 54449 USA. EM pfgiampietro@pediatrics.wisc.edu OI Blank, Robert Daniel/0000-0003-2950-1944 FU National Heart, Lung, and Blood Institute, Mammalian Genotyping Service [N01-HV-48141]; Beatrice and Samuel A. Seaver Foundation; Marshfield Clinic Research Foundation FX C.L.R., P.F.G., and R.D.B. contributed equally to this work. This work was supported by grants from the National Heart, Lung, and Blood Institute, Mammalian Genotyping Service N01-HV-48141, Beatrice and Samuel A. Seaver Foundation, and Marshfield Clinic Research Foundation. The authors thank Marshfield Clinic Research Foundation for its support through the assistance of Alice Stargardt in the preparation of this manuscript. This paper is Madison GRECC manuscript 2007-04. All authors state that there are no conflicts of interest. NR 41 TC 24 Z9 28 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD OCT PY 2009 VL 27 IS 10 BP 1366 EP 1372 DI 10.1002/jor.20885 PG 7 WC Orthopedics SC Orthopedics GA 498NJ UT WOS:000270147600016 PM 19340878 ER PT J AU Mao, JR AF Mao, Jianren TI Translational Pain Research: Achievements and Challenges SO JOURNAL OF PAIN LA English DT Review DE Translational research; pain; preclinical; clinical trial; animal study ID NMDA RECEPTOR ANTAGONIST; REFLEX SYMPATHETIC DYSTROPHY; PATIENT-CONTROLLED ANALGESIA; NEUROPATHIC PAIN; SODIUM-CHANNELS; NERVOUS-SYSTEM; DORSAL HORN; SPINAL-CORD; PERIPHERAL MONONEUROPATHY; ABDOMINAL HYSTERECTOMY AB The achievements in both preclinical and clinical pain research over the past 4 decades have led to significant progress in clinical pain management. However, pain research still faces enormous challenges and there remain many obstacles in the treatment of clinical pain, particularly chronic pain. Translational pain research needs to involve a number of important areas including: 1) bridging the gap between pain research and clinical pain management; 2) developing objective pain-assessment tools; 3) analyzing current theories of pain mechanisms and their relevance to clinical pain; 4) exploring new tools for both preclinical and clinical pain research; and 5) coordinating research efforts among basic scientists, clinical investigators, and pain-medicine practitioners. These issues are discussed in this article in light of the achievements and challenges of translational pain research. Perspective: The subjective nature of clinical pain calls for innovative research approaches. As translational pain research emerges as an important field in pain medicine, it will play a unique role in improving clinical pain management through coordinated bidirectional research approaches between bedside and bench. (c) 2009 by the American Pain Society C1 Harvard Univ, Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Dept Anesthesia & Crit Care,Sch Med, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Dept Anesthesia & Crit Care,Sch Med, Boston, MA 02114 USA. EM jmao@partners.org FU NIH [DA 22576, DE 18214, DA26002] FX Supported in part by NIH grants DA 22576, DE 18214, and DA26002. NR 147 TC 39 Z9 40 U1 0 U2 12 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD OCT PY 2009 VL 10 IS 10 BP 1001 EP 1011 DI 10.1016/j.jpain.2009.06.002 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 508GM UT WOS:000270917700001 PM 19628433 ER PT J AU Dobscha, SK Soleck, GD Dickinson, KC Burgess, DJ Lasarev, MR Lee, ES McFarland, BH AF Dobscha, Steven K. Soleck, Geoffrey D. Dickinson, Kathryn C. Burgess, Diana J. Lasarev, Michael R. Lee, Eun Sul McFarland, Bentson H. TI Associations Between Race and Ethnicity and Treatment for Chronic Pain in the VA SO JOURNAL OF PAIN LA English DT Article DE Veterans; pain; race/ethnicity ID HEALTH-CARE UTILIZATION; AFRICAN-AMERICANS; JOINT REPLACEMENT; KNEE ARTHROPLASTY; OLDER PATIENTS; DISPARITIES; OSTEOARTHRITIS; MANAGEMENT; ACCESS; PERCEPTIONS AB The purpose of this study was to identify racial and ethnic differences in patient-reported rates of treatment for chronic pain and ratings of pain-treatment effectiveness among veterans treated in Veterans Affairs(VA) facilities. This was a cross-sectional analysis of data from 255,522 veterans who participated in the VA Survey of the Healthcare Experiences of Patients (SHEP) in Fiscal Year 2005. Measures included demographics, the Veterans Rand Health Survey-12, a single item inquiring if the patient received treatment for chronic pain in the VA within the prior 12 months, and a single item asking the patient to rate the effectiveness of chronic pain care. in a logistic model adjusting for demographics, pain interference, and mental health status, male and female veterans who were Hispanic (OR 1.39 [95%CI 1.26-1.53] and OR 1.57 [1.02-2.43], respectively) or nonHispanic black (OR 1.43 [1.33-1.54] and OR 1.35 [1.02-1.78], respectively) were more likely to report receiving treatment for chronic pain in the prior 12 months compared to nonHispanic white veterans. Among veterans who reported receiving treatment for chronic pain, nonHispanic black men were less likely to rate pain-treatment effectiveness as very good or excellent, compared to nonHispanic white men (OR .809 [.720-.910]). Perspective: in our study, Hispanic and nonHispanic black veterans reported receiving chronic pain treatment more frequently than white veterans. Among veterans reporting pain treatment, nonHispanic black men were somewhat less likely to report receiving highly effective treatment than white men. Further research is needed to understand the reasons for these differences and their potential clinical implications. (c) 2009 by the American Pain Society C1 [Dobscha, Steven K.; Soleck, Geoffrey D.; Dickinson, Kathryn C.; Lasarev, Michael R.; Lee, Eun Sul] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Portland, OR 97207 USA. [Dobscha, Steven K.; McFarland, Bentson H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Lee, Eun Sul; McFarland, Bentson H.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Lasarev, Michael R.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. [Burgess, Diana J.] Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Burgess, Diana J.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, POB 1034 P3MHADM, Portland, OR 97207 USA. EM steven.dobscha@va.gov RI Burgess, Diana/A-1946-2016; OI McFarland, Bentson/0000-0001-9149-5616 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [PMI 03-195, RCD 04129, REA 06-174] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Projects PMI 03-195, RCD 04129 and REA 06-174. NR 47 TC 17 Z9 17 U1 2 U2 10 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD OCT PY 2009 VL 10 IS 10 BP 1078 EP 1087 DI 10.1016/j.jpain.2009.04.018 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 508GM UT WOS:000270917700010 PM 19800567 ER PT J AU Quintanilla-Dieck, MD Artunduaga, MA Eavey, RD AF Quintanilla-Dieck, Maria de Lourdes Artunduaga, Maria Alexandra Eavey, Roland D. TI Intentional Exposure to Loud Music: The Second MTV.com Survey Reveals an Opportunity to Educate SO JOURNAL OF PEDIATRICS LA English DT Article ID HEARING-LOSS; AGE AB Objectives Music-induced hearing loss (MIHL), an unconsciously self-inflicted public health concern, could evolve into an epidemic because of the appeal of loud music. After media attention about a previous hearing-loss survey with Music Television (MTV.com), we hypothesized that a repeat survey could compare awareness and behavior trends. Study design We incorporated the 2002 survey into the new 73-question instrument presented to random visitors on the MTV.com website in 2007. A P < .05 value was used for independent t and z- tests. Results A total of 2500 completed surveys were analyzed. Hearing loss was considered a problem by 32% of respondents compared with other health issues such as drug/alcohol use (62%). However, nearly half of the respondents admitted experiencing symptoms such as tinnitus or hearing loss after loud music exposure. Health care providers were the least likely source of MIHL awareness despite the respondents favoring provider education for hearing protection behavior modification. Conclusion Most respondents still could not recall learning about prevention of potential hearing loss, although the media has become the most informative source. Most respondents indicated that they would adopt protective ear behavior if made aware of hearing loss risk, especially if informed by health care professionals, revealing an educational opportunity. (J Pediatr 2009; 155:550-5). C1 [Quintanilla-Dieck, Maria de Lourdes; Artunduaga, Maria Alexandra; Eavey, Roland D.] Harvard Univ, Sch Med, Dept Otol & Laryngol,Dept Otolaryngol, Massachusetts Eye & Ear Infirm,Pediat Otolaryngol, Boston, MA 02115 USA. [Eavey, Roland D.] Vanderbilt Univ, Sch Med, Vanderbilt Bill Wilkerson Ctr Otolaryngol & Commu, Dept Otolaryngol, Nashville, TN 37212 USA. [Eavey, Roland D.] Vanderbilt Univ, Sch Med, Dept Speech & Hearing Sci, Nashville, TN 37212 USA. RP Eavey, RD (reprint author), Med Ctr E, Vanderbilt Bill Wilkerson Commun Ctr, South Tower,6th Floor,1215 21t Ave S, Nashville, TN 37232 USA. EM ron.eavey@vanderbilt.edu NR 19 TC 19 Z9 19 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2009 VL 155 IS 4 BP 550 EP 555 DI 10.1016/j.jpeds.2009.04.053 PG 6 WC Pediatrics SC Pediatrics GA 502YT UT WOS:000270497800021 ER PT J AU Lockenhoff, CE Ironson, GH O'Cleirigh, C Costa, PT AF Loeckenhoff, Corinna E. Ironson, Gail H. O'Cleirigh, Conall Costa, Paul T., Jr. TI Five-Factor Model Personality Traits, Spirituality/Religiousness, and Mental Health Among People Living With HIV SO JOURNAL OF PERSONALITY LA English DT Article ID QUALITY-OF-LIFE; PSYCHOLOGICAL ADJUSTMENT; RELIGION; SPIRITUALITY; METAANALYSIS; WOMEN; STRATEGIES; MEDIATION; ATTITUDES; DISTRESS AB We examined the association between five-factor personality domains and facets and spirituality/religiousness as well as their joint association with mental health in a diverse sample of people living with HIV (n=112, age range 18-66). Spirituality/religiousness showed stronger associations with Conscientiousness, Openness, and Agreeableness than with Neuroticism and Extraversion. Both personality traits and spirituality/religiousness were significantly linked to mental health, even after controlling for individual differences in demographic measures and disease status. Personality traits explained unique variance in mental health above spirituality and religiousness. Further, aspects of spirituality and religiousness were found to mediate some of the links between personality and mental health in this patient sample. These findings suggest that underlying personality traits contribute to the beneficial effects of spirituality/religiousness among vulnerable populations. C1 [Loeckenhoff, Corinna E.; Costa, Paul T., Jr.] NIA, Bethesda, MD 20892 USA. [Ironson, Gail H.] Univ Miami, Coral Gables, FL 33124 USA. [O'Cleirigh, Conall] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Fenway Inst, Cambridge, MA 02138 USA. RP Lockenhoff, CE (reprint author), Cornell Univ, Dept Human Dev, MVR G27-35, Ithaca, NY 14853 USA. EM CEL72@cornell.edu OI Costa, Paul/0000-0003-4375-1712; Loeckenhoff, Corinna/0000-0003-1605-1323 FU Intramural NIH HHS [NIH0011894836, Z01 AG000184-19]; NIMH NIH HHS [R01 MH066697, R01MH066697, R01MH53791] NR 62 TC 16 Z9 17 U1 0 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3506 J9 J PERS JI J. Pers. PD OCT PY 2009 VL 77 IS 5 BP 1411 EP 1436 DI 10.1111/j.1467-6494.2009.00587.x PG 26 WC Psychology, Social SC Psychology GA 490LS UT WOS:000269503000007 PM 19686457 ER PT J AU Stern, SL Dhanda, R Hazuda, HP AF Stern, Stephen L. Dhanda, Rahul Hazuda, Helen P. TI Helplessness predicts the development of hypertension in older Mexican and European Americans SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Depression; Elderly; Ethnicity; Helplessness; Hypertension ID AMBULATORY BLOOD-PRESSURE; DEPRESSIVE SYMPTOMS; SOCIOCULTURAL STATUS; RISK-FACTORS; DISEASE; HEALTH; POPULATION; ANXIETY; WOMEN; SCALE AB Objective: The mechanisms by which depression is associated with an elevated risk of cardiovascular disease remain unclear. It is possible that depressive symptoms could increase the risk of hypertension, which in turn could predispose to cardiovascular disease. The goal of this study was to explore whether individual depressive symptoms might predict the incidence of hypertension in a cohort of 240 initially normotensive Mexican-American and European-American elders. Methods: Subjects were 65-78 years old on entering the San Antonio Longitudinal Study of Aging, an epidemiologic survey, at which time they completed the 30-item Geriatric Depression Scale in English or Spanish. Their blood pressure was reassessed a mean of 7.0 years later. Responses to six key scale items (depressed mood, decreased interest, worthlessness, hopelessness, helplessness, and fatigue) were evaluated for the ability to predict incident hypertension. Results: In univariate analyses, only helplessness significantly predicted incident hypertension (chi-square 13.5, df=1, P=.0003). In a Cox proportional hazards model adjusted for sex, education, number of comorbid diseases, current drinking, social well-being, and marital status, helplessness remained a very strong predictor [hazard ratio (HR) 4.99: 95% confidence interval (CI) 1.90-13.12, P=.0011]. Total depression score also predicted incident hypertension, but less strongly (HR 1.08, CI 1.00-1.17, P=.0339). Conclusion: Helplessness may predict the development of hypertension in the elderly. Further research into this relationship might lead to interventions to reduce the risk of cardiovascular disease. (C) 2009 Elsevier Inc. All rights reserved. C1 [Stern, Stephen L.] S Texas Vet Hlth Care Syst, Psychiat Serv, San Antonio, TX USA. [Stern, Stephen L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Dhanda, Rahul] Ikaria, Clinton, NJ USA. [Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Stern, SL (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Psychiat Serv 116A, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM stephen.stern@va.gov FU NIA [R01-AG10444, R01-AG16518]; NIH [MO1-RR-01346] FX This work was supported by NIA Grant R01-AG10444 (San Antonio Longitudinal Study of Aging), NIA Grant R01-AG16518 (Disablement in an Aging, Bi-ethnic Cohort), and NIH Grant MO1-RR-01346 (Frederic C. Barrier Clinical Research Center). NR 32 TC 8 Z9 8 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD OCT PY 2009 VL 67 IS 4 BP 333 EP 337 DI 10.1016/j.jpsychores.2009.04.007 PG 5 WC Psychiatry SC Psychiatry GA 503VA UT WOS:000270567700008 PM 19773026 ER PT J AU Xu, YB Liu, JC Li, P Donellan, MB Parrett, BM Winograd, JM AF Xu, Yang-Bin Liu, Junchi Li, Ping Donellan, Matthias B. Parrett, Brian M. Winograd, Jonathan M. TI The Phrenic Nerve as a Motor Nerve Donor for Facial Reanimation with the Free Latissimus Dorsi Muscle SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE Facial reanimation; phrenic nerve; facial paralysis ID RECTUS-ABDOMINIS MUSCLE; BRACHIAL-PLEXUS INJURY; PARALYZED FACE; PULMONARY-FUNCTION; TRANSPLANTATION; PALSY; STAGE; RECONSTRUCTION; TRANSFERS; RESTORATION AB Free functional muscle transfer for acquired facial paralysis most often involves two stages. In this report, we describe single-stage free muscle transfer using the phrenic nerve as the donor motor nerve. Six patients with unilateral facial paralysis underwent single-stage facial reanimation using a free latissimus dorsi muscle with the ipsilateral phrenic nerve as the donor nerve. These cases were retrospectively studied to review technique and to determine outcomes including time to muscle reinnervation, patient satisfaction, smile symmetry, and complications. The mean age was 33 years. Five patients had complete unilateral facial paralysis and one had incomplete. There was no flap loss. The transferred muscle demonstrated active contraction in all patients at a mean of 14 weeks postoperatively (range, 12 to 16 weeks). Good dynamic symmetry was achieved by 6 to 9 months in all patients. All patients underwent rehabilitation including nerve reeducation. No clinically significant pulmonary morbidity was observed after the unilateral transection of the phrenic nerve. Using the phrenic nerve in free muscle transfer for facial paralysis allows a single-stage procedure with no requirement for nerve grafting and a rapid reinnervation time, shortening the time required for restoring facial animation. C1 [Donellan, Matthias B.; Parrett, Brian M.; Winograd, Jonathan M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Xu, Yang-Bin; Liu, Junchi; Li, Ping] Sun Yat Sen Univ, Dept Plast & Reconstruct Surg, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China. RP Winograd, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St,Wang 435, Boston, MA 02114 USA. EM jwinograd@partners.org NR 34 TC 5 Z9 5 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD OCT PY 2009 VL 25 IS 8 BP 457 EP 463 DI 10.1055/s-0029-1223851 PG 7 WC Surgery SC Surgery GA 508QW UT WOS:000270949100001 PM 19701878 ER PT J AU Schumacher, HR Taylor, W Edwards, L Grainger, R Schlesinger, N Dalbeth, N Sivera, F Singh, J Evans, R Waltrip, RW Diaz-Torne, C Macdonald, P Mcqueen, F Perez-Ruiz, F AF Schumacher, H. Ralph Taylor, William Edwards, Lawrence Grainger, Rebecca Schlesinger, Naomi Dalbeth, Nicola Sivera, Francisca Singh, Jasvinder Evans, Robert Waltrip, Royce W. Diaz-Torne, Cesar Macdonald, Patricia Mcqueen, Fiona Perez-Ruiz, Fernando TI Outcome Domains for Studies of Acute and Chronic Gout SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 9th International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials (OMERACT 9) CY MAY 27-31, 2008 CL Kananaskis, CANADA DE GOUT; OUTCOME MEASURES; CLINICAL TRIALS; OMERACT ID HYPERURICEMIA AB Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain, joint swelling, joint tenderness, patient global assessment and activity limitations. For studies in chronic gout 7 essential domains are: serum urate, acute gout attacks, tophus burden, health-related quality of life. activity limitations, pain, and patient global assessment. Implications of patient perspectives, discretionary domains for specific studies, measurement instruments and a possible responder index are under study. (J Rheumatol 2009:36:2342-5; doi: 10.3899/jrheum.090370) C1 [Taylor, William] Univ Otago, Wellington Sch Med & Hlth Sci, Rehabil Teaching & Res Unit, Wellington, New Zealand. [Edwards, Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Grainger, Rebecca] Malaghan Inst Med Res, Wellington, New Zealand. [Schlesinger, Naomi] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA. [Dalbeth, Nicola; Mcqueen, Fiona] Univ Auckland, Dept Med, Auckland, New Zealand. [Sivera, Francisca] Gen Hosp Univ Alicante, Secc Reumatol, E-03080 Alicante, Spain. [Singh, Jasvinder] Vet Affairs Med Ctr, Rheumatol Sect, Minneapolis, MN USA. [Singh, Jasvinder] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Evans, Robert] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Waltrip, Royce W.] Savient Pharmaceut, E Brunswick, NJ USA. [Diaz-Torne, Cesar] Hosp Santa Creu & Sant Pau, Barcelona, Spain. Takeda Pharmaceut Prod Inc, Lake Forest, IL USA. [Perez-Ruiz, Fernando] Hosp Cruces, Secc Reumatol, Vizcaya, Spain. [Schumacher, H. Ralph] Vet Affairs Med Ctr, Rheumatol Sect, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Vet Affairs Med Ctr, Rheumatol Sect, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu; fperez@hcru.osakidetza.net RI PEREZ-RUIZ, FERNANDO/E-4844-2012; OI singh, jasvinder/0000-0003-3485-0006; Cesar, Diaz-Torne/0000-0001-6275-7699; Perez-Ruiz, Fernando/0000-0002-5268-1894 NR 12 TC 52 Z9 55 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2009 VL 36 IS 10 BP 2342 EP 2345 DI 10.3899/jrheum.090370 PG 4 WC Rheumatology SC Rheumatology GA 505KB UT WOS:000270691200035 PM 19820223 ER PT J AU Grainger, R Taylor, WJ Dalbeth, N Perez-Ruiz, F Singh, JA Waltrip, RW Schlesinger, N Evans, R Edwards, NL Sivera, F Diaz-Torne, C Macdonald, PA Mcqueen, FM Schumacher, HR AF Grainger, Rebecca Taylor, William J. Dalbeth, Nicola Perez-Ruiz, Fernando Singh, Jasvinder A. Waltrip, Royce W. Schlesinger, Naomi Evans, Robert Edwards, N. Lawrence Sivera, Francisca Diaz-Torne, Cesar Macdonald, Patricia A. Mcqueen, Fiona M. Schumacher, H. Ralph TI Progress in Measurement Instruments for Acute and Chronic Gout Studies SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 9th International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials (OMERACT 9) CY MAY 27-31, 2008 CL Kananaskis, CANADA DE GOUT; OUTCOME MEASURES; INSTRUMENTS ID QUALITY-OF-LIFE; DOUBLE-BLIND; ASSESSMENT QUESTIONNAIRE; PHYSICAL MEASUREMENT; OUTCOME MEASURES; CONTROLLED-TRIAL; ARTHRITIS; INDOMETHACIN; ETORICOXIB; FEBUXOSTAT AB Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the Gout workshop, in breakout groups, and at informal meetings of the gout group. In acute gout, instruments for domains of pain, joint swelling. joint tenderness, and patient and physician global assessment have been assessed. In chronic gout, some validation exercises have been performed in instruments for domains serum urate, tophus measurement, health-related quality of life (HRQOL). In voting at OMERACT 9, the Medical Outcomes Study Short-Form 36 was endorsed as a valid instrument for measurement of HRQOL. Methods of tophus measurement were considered to have met some criteria of the OMERACT filter, but these require further work, particularly regarding sensitivity to change over shorter time periods. Priorities for future research include measurement of joint inflammation in acute gout and disability in acute and chronic gout. (J Rheumatol 2009;36:2346-55; doi: 10.3899/jrheum.090371) C1 [Grainger, Rebecca] Univ Otago, Dept Med, Wellington 6242, New Zealand. Univ Otago, Malaghan Inst Med Res, Rehabil Teaching & Res Unit, Wellington 6242, New Zealand. [Dalbeth, Nicola; Mcqueen, Fiona M.] Univ Auckland, Dept Med, Auckland, New Zealand. [Perez-Ruiz, Fernando] Hosp Cruces, Secc Reumatol, Vizcaya, Spain. [Singh, Jasvinder A.] Vet Affairs Med Ctr, Rheumatol Sect, Minneapolis, MN USA. [Singh, Jasvinder A.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Waltrip, Royce W.] Savient Pharmaceut, E Brunswick, NJ USA. [Schlesinger, Naomi] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA. [Evans, Robert] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Miami, FL USA. [Sivera, Francisca] Gen Hosp Univ Alicante, Secc Reumatol, E-03080 Alicante, Spain. [Diaz-Torne, Cesar] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Macdonald, Patricia A.] TAP Pharmaceut Prod Inc, Lake Forest, IL USA. [Schumacher, H. Ralph] Vet Affairs Med Ctr, Philadelphia, PA USA. RP Taylor, WJ (reprint author), Univ Otago, Dept Med, POB 7343, Wellington 6242, New Zealand. EM will.taylor@otago.ac.nz RI PEREZ-RUIZ, FERNANDO/E-4844-2012; Grainger, Rebecca/I-1866-2012; OI singh, jasvinder/0000-0003-3485-0006; Cesar, Diaz-Torne/0000-0001-6275-7699; Perez-Ruiz, Fernando/0000-0002-5268-1894 NR 39 TC 33 Z9 36 U1 0 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2009 VL 36 IS 10 BP 2346 EP 2355 DI 10.3899/jrheum.090371 PG 10 WC Rheumatology SC Rheumatology GA 505KB UT WOS:000270691200036 PM 19820224 ER PT J AU Saikachi, Y Stevens, KN Hillman, RE AF Saikachi, Yoko Stevens, Kenneth N. Hillman, Robert E. TI Development and Perceptual Evaluation of Amplitude-Based F0 Control in Electrolarynx Speech SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article ID ALARYNGEAL SPEECH; VOICE QUALITY; LARYNGECTOMY; ENHANCEMENT; FREQUENCY; REHABILITATION; COMMUNICATION; INFORMATION; SYNTHESIZER; MANDARIN AB Purpose: Current electrolarynx (EL) devices produce a mechanical speech quality that has been largely attributed to the lack of natural fundamental frequency (F0) variation. In order to improve the quality of EL speech, in the present study the authors aimed to develop and evaluate an automatic F0 control scheme, in which F0 was modulated based on variations in the root-mean-square (RMS) amplitude of the EL speech signal. Method: Recordings of declarative sentences produced by 2 male participants before and after total laryngectomy were used to develop procedures for calculating F0 contours for EL speech. Specifically, the positive linear relationship between F0 and RMS amplitude observed in pre-laryngectomy speech was used as the basis for generating an F0 contour based on the amplitude variation of EL speech. An analysis-by-synthesis approach was used to modify the F0 contour, and a perceptual experiment was conducted to examine its impact on the quality of the EL speech. Results: The results of perceptual experiments showed that modulating the F0 of EL speech using a linear relationship between amplitude and frequency made it significantly more natural sounding than EL speech with constant F0. Conclusions: The current study provides preliminary support for amplitude-based control of F0 in EL speech. C1 [Hillman, Robert E.] Massachusetts Gen Hosp, Voice Ctr, Boston, MA 02114 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Saikachi, Yoko] Harvard Univ, MIT Div Hlth Sci & Technol, Cambridge, MA 02138 USA. [Stevens, Kenneth N.] MIT, Cambridge, MA 02139 USA. RP Hillman, RE (reprint author), Massachusetts Gen Hosp, Voice Ctr, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM hillman.robert@mgh.harvard.edu FU NIDCD NIH HHS [R01 DC006449, R41 DC008722, R41 DC008722-01A1] NR 51 TC 6 Z9 6 U1 0 U2 1 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT 1 PY 2009 VL 52 IS 5 BP 1360 EP 1369 DI 10.1044/1092-4388(2009/08-0167) PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 498KX UT WOS:000270140100017 PM 19564438 ER PT J AU Dookeran, NM Burgess, JF Bowman, CC Goetz, MB Asch, SM Gifford, AL AF Dookeran, Nameeta M. Burgess, James F., Jr. Bowman, Candice C. Goetz, Matthew Bidwell Asch, Steven M. Gifford, Allen L. TI HIV screening among substance-abusing veterans in care SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE HIV screening; HIV testing; HIV risk; Alcohol use disorders; Substance use disorders ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG-USERS; COST-EFFECTIVENESS; UNITED-STATES; ANTIRETROVIRAL THERAPY; SEXUAL TRANSMISSION; ALCOHOL-CONSUMPTION; RISK; INFECTION; RECOMMENDATIONS AB Calls for screening for HIV infection among individuals with substance use disorders, including alcohol use, are increasing. We investigated HIV screening and its predictors in the Veterans Health Administration (VA) system among such individuals in care. Our primary outcome was retrospective evidence of screening for HIV infection, adjusting for patient demographics and important comorbid disease. Of the 371,749 sample patients with histories of substance use disorders using VA services, 20% had evidence of HIV screening. Screening was lowest among those with alcohol use disorders alone (11%) and highest among those treated in substance use programs (28%) or receiving inpatient care (28%). The findings suggest a low recognition of substance use disorders (especially alcohol use) as risk factors for HIV. Quality improvement initiatives to increase risk factor recognition and screening among patients with substance use disorders will yield benefits in the fight against HIV. (C) 2009 Elsevier Inc. All rights reserved. C1 [Dookeran, Nameeta M.] Brigham & Womens Hosp, Dept Med, Brigham & Womens Hospitalist Serv, Boston, MA 02115 USA. [Dookeran, Nameeta M.; Gifford, Allen L.] Edith Nourse Rogers Mem Vet Adm Hosp, VA HSR&D Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA. [Burgess, James F., Jr.; Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Bowman, Candice C.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, HIV Hepatitis Qual Enhancement Res Initiat, Los Angeles, CA 90073 USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Gifford, Allen L.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Dookeran, NM (reprint author), Brigham & Womens Hosp, Dept Med, Brigham & Womens Hospitalist Serv, 75 Francis St,PBB B-428, Boston, MA 02115 USA. EM ndookeran@partners.org OI Burgess, James/0000-0002-6646-7071; Goetz, Matthew/0000-0003-4542-992X NR 40 TC 4 Z9 4 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD OCT PY 2009 VL 37 IS 3 BP 286 EP 291 DI 10.1016/j.jsat.2009.03.003 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 497FY UT WOS:000270044200008 PM 19346096 ER PT J AU Sala, FG Kunisaki, SM Ochoa, ER Vacanti, J Grikscheit, TC AF Sala, Frederic G. Kunisaki, Shaun M. Ochoa, Erin R. Vacanti, Joseph Grikscheit, Tracy C. TI Tissue-Engineered Small Intestine and Stomach Form from Autologous Tissue in a Preclinical Large Animal Model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the Society-of-University-Surgeons/4th Annual Academic Surgical Congress CY FEB 03-06, 2009 CL Ft Myers, FL SP Soc Univ Surg, Assoc Acad Surg DE tissue engineering; small intestine; preclinical large animal model; short bowel syndrome; intestinal stem cell niche ID NEONATAL NECROTIZING ENTEROCOLITIS; EPITHELIAL STEM-CELL; SUBEPITHELIAL MYOFIBROBLASTS; IN-VIVO; MORTALITY; INFANTS; PATTERN; INJURY; BIRTH; UNITS AB Background. Tissue-engineered small intestine, stomach, large intestine, esophagus, and gastroesophageal (GE) junction have been successfully formed from syngeneic cells, and employed as a rescue therapy in a small animal model. The purpose of this study is to determine if engineered intestine and stomach could be generated in an autologous, preclinical large animal model, and to identify if the tissue-engineered intestine retained features of an intact stem cell niche. Methods. A short segment of jejunum or stomach was resected from 6-wk-old Yorkshire swine. Organoid units, multicellular clusters with predominantly epithelial content, were generated and loaded onto biodegradable scaffold tubes. The constructs were then implanted intraperitoneally in the autologous host. Seven wk later, all implants were harvested and analyzed using histology and immunohistochemistry techniques. Results. Autologous engineered small intestine and stomach formed. Tissue-engineered intestinal architecture replicated that of native intestine. Histology revealed tissue-engineered small intestinal mucosa composed of a columnar epithelium with all differentiated intestinal cell types adjacent to an innervated muscularis mucosae. Intestinal subepithelial myofibroblasts, specialized cells that participate in the stem cell niche formation, were identified. Moreover, cells positive for the putative intestinal stem cell marker, doublecortin and CaM kinase-like-1 (DCAMEKL-1) expression were identified at the base of the crypts. Finally, tissue-engineered stomach also formed with antral-type mucosa (mucus cells and surface foveolar cells) and a muscularis. Conclusion. We successfully generated tissue-engineered intestine with correct architecture, including features of an intact stem cell niche, in the pig model. To our knowledge, this is the first demonstration in which tissue-engineered intestine was successfully generated in an autologous manner in an animal model, which may better emulate a human host and the intended therapeutic pathway for humans. (C) 2009 Elsevier Inc. All rights reserved. C1 [Sala, Frederic G.; Grikscheit, Tracy C.] Childrens Hosp Los Angeles, Saban Res Inst, Dev Biol & Regenerat Med Program, Los Angeles, CA 90027 USA. [Kunisaki, Shaun M.; Ochoa, Erin R.; Vacanti, Joseph] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Grikscheit, TC (reprint author), Childrens Hosp Los Angeles, Saban Res Inst, Dev Biol & Regenerat Med Program, 4650 W Sunset Blvd,MS 35, Los Angeles, CA 90027 USA. EM tgrikscheit@chla.usc.edu NR 43 TC 70 Z9 71 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2009 VL 156 IS 2 BP 205 EP 212 DI 10.1016/j.jss.2009.03.062 PG 8 WC Surgery SC Surgery GA 503TW UT WOS:000270564300005 PM 19665143 ER PT J AU de Moya, MA Zacharias, N Osbourne, A Butt, MU Alam, HB King, DR McGovern, F Velmahos, GC AF de Moya, Marc A. Zacharias, Nikolaos Osbourne, Audley Butt, Muhammad Umar Alam, Hasan B. King, David R. McGovern, Francis Velmahos, George C. TI Colovesical Fistula Repair: Is Early Foley Catheter Removal Safe? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the Society-of-University-Surgeons/4th Annual Academic Surgical Congress CY FEB 03-06, 2009 CL Ft Myers, FL SP Soc Univ Surg, Assoc Acad Surg DE colovesicular fistula; diverticulitis; Foley catheter ID ENTEROVESICAL FISTULAS; MANAGEMENT; DIAGNOSIS; SPECTRUM; DISEASE; BLADDER AB Background. Colovesical fistula (CVF) are the most common occurring fistulae secondary to diverticulitis. Review of the literature reveals great variability in postoperative Foley catheter management, as well as the role of a cystogram. The purpose of this study was to review our experience in early vs. late removal of the Foley catheter after CVF repair secondary to diverticulitis. Our hypothesis was that early Foley catheter removal is not associated with increased complications, and postoperative cystogram is of low value. Methods. This is a retrospective study (January 2002-March 2008) of all patients with a diagnosis of CVF secondary to diverticulitis, who were treated with a sigmoidectomy and takedown of the fistula. Hospital records were reviewed and demographics, days to Foley removal, performance of cystogram, type of repair, complications, and comorbidities were recorded. Patients were separated into two groups according to early or late Foley catheter removal. Removal of the Foley catheter in <= 7 d was considered early, and removal in > 7d was considered late. Results. Thirty-two patients were identified, with a mean age of 65.2 y (42-91). Mean duration of Foley catheter stay was 15.6 d (3-42). Six patients had early postoperative Foley catheter removal and 26 patients had late Foley catheter removal. Four patients had complex bladder repair, and they all had late Foley catheter removal. From the 28 patients with simple bladder repair, six had early removal and 22 had late removal. Patients with early Foley catheter removal did not have significant complications compared with patients with late Foley catheter removal. Eleven patients got a cystogram postoperatively to detect possible bladder leaks. All cystograms performed were negative. Conclusions. Patients with a diagnosis of CVF secondary to diverticulitis may have their Foley catheter removed in 7 d without any increased complications. The role of the cystogram is unclear; however, no value was added in simple bladder repairs. (C) 2009 Elsevier Inc. All rights reserved. C1 [de Moya, Marc A.; Zacharias, Nikolaos; Butt, Muhammad Umar; Alam, Hasan B.; King, David R.; McGovern, Francis; Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Osbourne, Audley] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Osbourne, Audley] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM mdemoya@partners.org OI King, David/0000-0003-1028-1478 NR 16 TC 6 Z9 6 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2009 VL 156 IS 2 BP 274 EP 277 DI 10.1016/j.jss.2009.03.094 PG 4 WC Surgery SC Surgery GA 503TW UT WOS:000270564300016 PM 19665732 ER PT J AU Butt, MU Sailhamer, EA Li, YQ Liu, BL Shuja, F Velmahos, GC deMoya, M King, DR Alam, HB AF Butt, Muhammad U. Sailhamer, Elizabeth A. Li, Yongqing Liu, Baoling Shuja, Fahad Velmahos, George C. deMoya, Marc King, David R. Alam, Hasan B. TI Pharmacologic Resuscitation: Cell Protective Mechanisms of Histone Deacetylase Inhibition in Lethal Hemorrhagic Shock SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the Society-of-University-Surgeons/4th Annual Academic Surgical Congress CY FEB 03-06, 2009 CL Ft Myers, FL SP Soc Univ Surg, Assoc Acad Surg DE acetylation; liver; hemorrhage; resuscitation; shock; valproic acid ID NF-KAPPA-B; REACTIVE OXYGEN; VALPROIC ACID; CARDIAC HISTONES; ACETYLATION; ACTIVATION; DEATH; JNK; COACTIVATORS; STRATEGIES AB Background. We have demonstrated that valproic acid (VPA), a histone deacetylase inhibitor (HDACI), can improve animal survival after hemorrhagic shock, and protect neurons from hypoxia-induced apoptosis. This study investigated whether VPA treatment works through the c-Jun N-terminal kinase (JNK)/Caspase-3 survival pathways. Methods. Wistar-Kyoto rats underwent hemorrhagic shock (60% blood loss over 60 min) followed by post-shock treatment with VPA (300 mg/kg), without any additional resuscitation fluids. The experimental groups were: (1) Sham (no hemorrhage, no resuscitation), (2) no resuscitation (hemorrhage, no resuscitation), and (3) VPA treatment. The animals were sacrificed at 1, 6, or 24 h (n = 3/timepoint), and liver tissue was harvested. Cytosolic and nuclear proteins were isolated and analyzed for acetylated histone-H3 at lysine-9 (Ac-H3K9), total and phosphorylated JNK, and activated caspase-3 by Western blot. Results. Hemorrhaged animals were in severe shock, with mean arterial pressures of 25-30 mmHg and lactic acid 7-9 mg/dL. As expected, only the VPA treated animals survived to the 6- and 24-h timepoints; none of the non-resuscitated animals survived to these time points. Treatment of hemorrhaged animals with VPA induced acetylation of histone H3K9, which peaked at 1 h and returned back to normal by 24 h. Hemorrhage induced phosphorylation of JNK (active form) and increased activated caspase-3 levels, representing a commitment to subsequent cell death. Treatment with VPA decreased the phospho-JNK (P = 0.06) expression at 24 h, without changing the total levels of JNK (P = 0.89), and this correlated with attenuation of activated caspase-3 at 24 h (P = 0.04), compared with the non-resuscitated animals. Conclusion. Treatment with HDACI, induces acetylation of histone H3K9, and reduces JNK phosphorylation and subsequent caspase-3 activation. This discovery establishes for the first time that HDACI may protect cells after severe hemorrhage through modulation of the JNK/caspase-3 apoptotic pathway. (C) 2009 Elsevier Inc. All rights reserved. C1 [Butt, Muhammad U.; Sailhamer, Elizabeth A.; Li, Yongqing; Liu, Baoling; Shuja, Fahad; Velmahos, George C.; deMoya, Marc; King, David R.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org OI King, David/0000-0003-1028-1478 FU NIGMS NIH HHS [F32 GM79880] NR 23 TC 29 Z9 35 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2009 VL 156 IS 2 BP 290 EP 296 DI 10.1016/j.jss.2009.04.012 PG 7 WC Surgery SC Surgery GA 503TW UT WOS:000270564300019 PM 19665733 ER PT J AU Nykiel, S AF Nykiel, Sherry TI Music Therapy Groupwork With Special Needs Children: The Evolving Process SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Nykiel, Sherry] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nykiel, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM snykiel@partners.org NR 1 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2009 VL 48 IS 10 BP 1043 EP 1044 DI 10.1097/01.CHI.0000357898.98488.5b PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 499DH UT WOS:000270196600016 ER PT J AU Kelz, RR Tran, TT Hosokawa, P Henderson, W Paulson, EC Spitz, F Hamilton, BH Hall, BL AF Kelz, Rachel R. Tran, Timothy T. Hosokawa, Patrick Henderson, William Paulson, E. Carter Spitz, Francis Hamilton, Barton H. Hall, Bruce L. TI Time-of-Day Effects on Surgical Outcomes in the Private Sector: A Retrospective Cohort Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID 30-DAY POSTOPERATIVE MORTALITY; UNIVERSITY MEDICAL-CENTERS; VETERANS-AFFAIRS HOSPITALS; MYOCARDIAL-INFARCTION; EMERGENCY-SURGERY; INTENSIVE-CARE; MORBIDITY; RISK; OPERATIONS; SURVIVAL AB BACKGROUND: Surgical care is delivered around the clock. Elective cases within the Veterans Affairs health system starting after 4 Pm appear to have an elevated risk of morbidity, but not mortality, compared with earlier cases. The relationship between operation start time and patient outcomes is not described in private-sector patients or for emergency cases. STUDY DESIGN: We performed a retrospective cohort study of 56,920 general and vascular surgical procedures performed from October 2001 through September 2004, and entered into the National Surgical Quality Improvement Program database. Operation start time was the independent variable of interest. Random effects, hierarchical logistic regression models adjusted for patient, operative, and facility characteristics. Two independent models determined associations between start time and morbidity or mortality. Subset analysis was performed for emergency and nonemergency cases. RESULTS: After adjustment for patient and procedure characteristics, mortality had a moderately strong association with start time, but only for nonemergency cases starting 9:30 PM to 7:30 Am (odds ratio = 1.752; P = 0.028; reference 7:30 Am to 9:30 AM). As for morbidity, after adjustment, operations starting 9:30 AM to 1:30 PM mid 5:30 PM to 9:30 Pm were associated with a weakly elevated risk of morbidity, but those starting 9:30 PM to 7:30 AM demonstrated a strong effect on morbidity (odds ratio = 1.32; p < 0.0001). Subgroup analysis showed this effect was largely a result of elevated risk of morbidity in emergency cases from this overnight time period (odds ratio = 1.48; p = 0.001). CONCLUSIONS: Surgical start times are associated with risk-adjusted patient outcomes. In terms of facility operations management and resource allocation, consideration should be given to the capacity to accommodate cases with differences in risk during different time periods. (J Am Coll Surg 2009;209:434-445. (C) 2009 by the American College of Surgeons) C1 [Kelz, Rachel R.; Paulson, E. Carter; Spitz, Francis] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Kelz, Rachel R.; Spitz, Francis] Philadelphia VA Med Ctr, Dept Surg, Philadelphia, PA USA. [Tran, Timothy T.; Hall, Bruce L.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hosokawa, Patrick; Henderson, William] Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. [Hamilton, Barton H.; Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. RP Kelz, RR (reprint author), Univ Penn, Sch Med, Dept Surg, 3400 Spruce St,4 Silverstein, Philadelphia, PA 19104 USA. EM rachel.kelz@uphs.upenn.edu RI Hamilton, Barton/P-5187-2015 FU Office of Research and Development; Department of Veterans Affairs [693/11]; Center for Health Policy; Agency for Healthcare Research and Quality [5U18HS011913] FX This study does not represent the views of the ACS or the ACS NSQIP. This material is based upon work supported by the Office of Research and Development, competitive pilot project fund, Department of Veterans Affairs 693/11. Dr Hall was supported by the Center for Health Policy under the direction of Dr William Peck, Washington University in St Louis, St Louis, MO. This article is partially derived from the Patient Safety in Surgery Study, and partially supported by the Agency for Healthcare Research and Quality, grant number 5U18HS011913, entitled "Reporting System to Improve Patient Safety in Surgery." NR 21 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2009 VL 209 IS 4 BP 434 EP 445 DI 10.1016/j.jamcollsurg.2009.05.022 PG 12 WC Surgery SC Surgery GA 506CD UT WOS:000270749900003 PM 19801316 ER PT J AU Hill, JS McPhee, JT Whalen, GF Sullivan, ME Warshaw, AL Tseng, JF AF Hill, Joshua S. McPhee, James T. Whalen, Giles F. Sullivan, Mary E. Warshaw, Andrew L. Tseng, Jennifer F. TI In-Hospital Mortality after Pancreatic Resection for Chronic Pancreatitis: Population-Based Estimates from the Nationwide Inpatient Sample SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 93rd Annual Clinical Congress of the American-College-of-Surgeons CY OCT 07-11, 2007 CL New Orleans, LA SP Amer Coll Surg ID QUALITY-OF-LIFE; TERM-FOLLOW-UP; HEAD RESECTION; LATERAL PANCREATICOJEJUNOSTOMY; OPERATIVE MANAGEMENT; SURGICAL-TREATMENT; WHIPPLE PROCEDURE; PANCREATICODUODENECTOMY; DUCT; VOLUME AB BACKGROUND: Pancreatic resection can be performed to ameliorate the sequelae of chronic pancreatitis in selected patients. The perceived risk of pancreatectomy may limit its use. Using a national database, this study compared mortality after pancreatic resections for chronic pancreatitis with those performed for neoplasm. STUDY DESIGN: Patient discharges with chronic pancreatitis or pancreatic neoplasm were queried from the Nationwide Inpatient Sample, 1998 to 2006. To account for the Nationwide Inpatient Sample weighting schema, design-adjusted analyses were used. RESULTS: There were 11,048 pancreatic resections. Malignant neoplasms represented 64.2% of the sample; benign neoplasms and pancreatitis comprised 17.1% and 18.7%, respectively. In-hospital mortality rates were 2.2% and 1.7% for the pancrearitis and benign tumor cohorts, respectively, compared with 5.9% for the malignancy cohort (overall p < 0.01). A multivariable logistic regression examined differences in mortality among diagnoses while adjusting for patient and hospital characteristics; covariates included patient gender, race, age, comorbidities, type of pancreatectomy, payor, hospital teaching status, hospital size, and hospital volume. After adjustment, patients undergoing resection for pancreatitis were at a significantly lower risk of in-hospital mortality when compared with those with malignant neoplasm (odds ratio, 0.43; 95% CI, 0.28 to 0.67). CONCLUSIONS: Pancreatectomies for chronic pancreatitis have lower in-hospital mortality than those performed for malignancy and similar rates as resection for benign tumors. Pancreatic resection, which can improve quality of life in chronic pancreatitis patients, can be performed with moderate mortality rates and should be considered in appropriate patients. (J Am Coll Surg 2009;209:468-476. (C) 2009 by the American College of Surgeons) C1 [Tseng, Jennifer F.] Univ Massachusetts, Sch Med, Dept Surg, SOAR Res Lab, Worcester, MA 01655 USA. [Warshaw, Andrew L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Tseng, JF (reprint author), Univ Massachusetts, Sch Med, Dept Surg, SOAR Res Lab, S3-752,55 Lake Ave, Worcester, MA 01655 USA. FU Howard Hughes Medical Institute NR 35 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2009 VL 209 IS 4 BP 468 EP 476 DI 10.1016/j.jamcollsurg.2009.05.030 PG 9 WC Surgery SC Surgery GA 506CD UT WOS:000270749900007 PM 19801320 ER PT J AU Vagefi, PA Morse, CR AF Vagefi, Parsia A. Morse, Christopher R. TI Bochdalek Hernia in an Adult SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Editorial Material C1 [Vagefi, Parsia A.; Morse, Christopher R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Vagefi, PA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 2 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2009 VL 209 IS 4 BP 540 EP 540 DI 10.1016/j.jamcollsurg.2009.01.052 PG 1 WC Surgery SC Surgery GA 506CD UT WOS:000270749900013 PM 19801327 ER PT J AU Zhu, CW Penrod, JD Ross, JS Dellenbaugh, C Sano, M AF Zhu, Carolyn W. Penrod, Joan D. Ross, Joseph S. Dellenbaugh, Cornelia Sano, Mary TI Use of Medicare and Department of Veterans Affairs Health Care by Veterans with Dementia: A Longitudinal Analysis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; health services use; Medicare; veterans; longitudinal models ID ACUTE MYOCARDIAL-INFARCTION; ALZHEIMERS-DISEASE; UNITED-STATES; VA; COST; PREVALENCE; DISTANCE; SERVICES; SYSTEM AB The objectives of this study were to examine longitudinal patterns of Department of Veterans Affairs (VA)-only use, dual VA and Medicare use, and Medicare-only use by veterans with dementia. Data on VA and Medicare use were obtained from VA administrative datasets and Medicare claims (1998-2001) for 2,137 male veterans who, in 1997, used some VA services, had a formal diagnosis of Alzheimer's disease or vascular dementia in the VA, and were aged 65 and older. Generalized ordered logit models were used to estimate the effects of patient characteristics on use group over time. In 1998, 41.7% of the sample were VA-only users, 55.4% were dual users, and 2.9% were Medicare-only users. By 2001, 30.4% were VA-only users, 51.5% were dual users, and 18.1% were Medicare-only users. Multivariate results show that greater likelihood of Medicare use was associated with older age, being white, being married, having higher education, having private insurance or Medicaid, having low VA priority level, and living in a nursing home or dying during the year. Higher comorbidities were associated with greater likelihood of dual use as opposed to any single system use. Alternatively, number of functional limitations was associated with greater likelihood of Medicare-only use and less likelihood of VA-only use. These results imply that different aspects of veterans' needs have differential effects on where they seek care. Efforts to coordinate care between VA and Medicare providers are necessary to ensure that patients receive high-quality care, especially patients with multiple comorbidities. C1 [Zhu, Carolyn W.; Penrod, Joan D.; Ross, Joseph S.; Dellenbaugh, Cornelia; Sano, Mary] James J Peters Vet Affairs Med Ctr, Res Enhancement Award Program, Hlth Serv Res & Dev Serv, Bronx, NY 10468 USA. [Zhu, Carolyn W.; Penrod, Joan D.; Ross, Joseph S.; Dellenbaugh, Cornelia] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Zhu, Carolyn W.; Penrod, Joan D.; Ross, Joseph S.; Dellenbaugh, Cornelia; Sano, Mary] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Hlth Serv Res & Dev Serv, Bronx, NY 10468 USA. RP Zhu, CW (reprint author), James J Peters Vet Affairs Med Ctr, Res Enhancement Award Program, Hlth Serv Res & Dev Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM carolyn.zhu@mssm.edu FU VA HSRD [IIR 05-114, TRP-02-149] FX This project was supported by VA HSR&D IIR 05-114 (PI Zhu). Drs. Zhu, Penrod, and Ross also are supported by VA HSR&D TRP-02-149. NR 33 TC 7 Z9 7 U1 3 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2009 VL 57 IS 10 BP 1908 EP 1914 DI 10.1111/j.1532-5415.2009.02405.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 503PV UT WOS:000270551300025 PM 19682132 ER PT J AU Volandes, AE Mitchell, SL Gillick, MR Chang, YC Paasche-Orlow, MK AF Volandes, Angelo E. Mitchell, Susan L. Gillick, Muriel R. Chang, Yuchiao Paasche-Orlow, Michael K. TI Using Video Images to Improve the Accuracy of Surrogate Decision-Making: A Randomized Controlled Trial SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article ID SERIOUSLY ILL PATIENTS; HOSPITALIZED-PATIENTS; SUBSTITUTED JUDGMENT; CARE; LIFE; PREFERENCES; SUPPORT; END; COMMUNICATION; DEMENTIA AB Introduction: When patients are unable to make important end-of-life decisions, doctors ask surrogate decision makers to provide insight into patients' preferences. Unfortunately, multiple studies have shown that surrogates' knowledge of patient preferences is poor. We hypothesized that a video decision tool would improve concordance between patients and their surrogates for end-of-life preferences. Objective: To compare the concordance of preferences among elderly patients and their surrogates listening to only a verbal description of advanced dementia or viewing a video decision support tool of the disease after hearing the verbal description. Methods: This was a randomized controlled trial of a convenience sample of community-dwelling elderly subjects (>= 65 years) and their surrogates, and was conducted at 2 geriatric clinics affiliated with 2 academic medical centers in Boston. The study was conducted between September 1, 2007, and May 30, 2008. Random assignment of patient and surrogate dyads was to either a verbal narrative or a video decision support tool after the verbal narrative. End points were goals of care chosen by the patient and predicted goals of care by the surrogate. Goals of care included life-prolonging care (CPR, mechanical ventilation), limited care (hospitalization, antibiotics, but not CPR), and comfort care (only treatment to relieve symptoms). The primary outcome measure was the concordance rate of preferences between patients and their surrogates. Results: A total of 14 pairs of patients and their surrogates were randomized to verbal narrative (n = 6) or video after verbal narrative (n = 8). Among the 6 patients receiving only the verbal narrative, 3 (50%) preferred comfort care, 1 (17%) chose limited care, and 2 (33%) desired life-prolonging care. Among the surrogates for these patients, only 2 correctly chose what their loved one would want if in a state of advanced dementia, yielding a concordance rate of 33%. Among the 8 patients receiving the video decision support tool, all 8 chose comfort care. Among the surrogates for these patients, all 8 correctly chose what their loved one would want if in a state of advanced dementia, yielding a concordance rate of 100%. Conclusion: Patients and surrogates viewing a video decision support tool for advanced dementia are more likely to concur about the patient's end-of-life preferences than when solely listening to a verbal description of the disease. (J Am Med Dir Assoc 2009; 10: 575-580) C1 [Volandes, Angelo E.; Chang, Yuchiao] Massachusetts Gen Hosp, Gen Med Unit, Dept Med, Boston, MA 02114 USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Volandes, Angelo E.; Mitchell, Susan L.; Gillick, Muriel R.] Harvard Univ, Sch Med, Boston, MA USA. [Mitchell, Susan L.] Hebrew SeniorLife, Boston, MA USA. [Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Gillick, Muriel R.] Harvard Univ, Med Sch Harvard Pilgrim, Dept Ambulatory Care & Prevent, Boston, MA USA. [Paasche-Orlow, Michael K.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM avolandes@partners.org OI Paasche-Orlow, Michael/0000-0002-9276-7190 FU George Bennett Fellowship; Alzheimer's Association; Hartford Foundation FX Dr. Volandes was supported by a George Bennett Fellowship from the Foundation for Informed Medical Decision Making, a New Investigator Research Grant from the Alzheimer's Association, and a Center for Excellence Career Development Award from the Hartford Foundation. None of the Foundations participated in the collection, analysis, or interpretation of the data or in preparation, review, or approval of the manuscript. NR 25 TC 30 Z9 30 U1 4 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD OCT PY 2009 VL 10 IS 8 BP 575 EP 580 DI 10.1016/j.jamda.2009.05.006 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 514LZ UT WOS:000271397500008 PM 19808156 ER PT J AU Feng, XB Lu, TC Chuang, PY Fang, W Ratnam, K Xiong, HB Ouyang, XS Shen, YH Levy, DE Hyink, D Klotman, M D'Agati, V Iyengar, R Klotman, PE He, JC AF Feng, Xiaobei Lu, Ting-Chi Chuang, Peter Y. Fang, Wei Ratnam, Krishna Xiong, Huabao Ouyang, Xinshou Shen, Yuhong Levy, David E. Hyink, Deborah Klotman, Mary D'Agati, Vivette Iyengar, Ravi Klotman, Paul E. He, John C. TI Reduction of Stat3 Activity Attenuates HIV-Induced Kidney Injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID JAK/STAT SIGNALING PATHWAY; AIDS-LIKE DISEASE; TRANSGENIC MICE; DIABETIC-NEPHROPATHY; CELL DEVELOPMENT; NEF; EXPRESSION; PODOCYTES; PROLIFERATION; ACTIVATION AB HIV-1 Nef induces podocyte proliferation and dedifferentiation by activating the Stat3 and MAPK1,2 pathways. Activation of Stat3 also occurs in human kidneys affected by HIV-associated nephropathy (HIVAN), but its contribution to the development of HIVAN is unknown. Here, we generated HIV-1 transgenic mice (Tg26) with either 75% Stat3 activity (Tg26-SA/+) or 25% Stat3 activity (Tg26-SA/-). The kidneys of Tg26-SA/+ mice, but not Tg26-SA/- mice, showed increased Stat3 phosphorylation. The Tg26-SA/+ phenotype was not different from Tg26 mice, but Tg26-SA/- mice developed significantly less proteinuria, glomerulosclerosis, and tubulointerstitial injury. Tg26-SA/+ mice exhibited reduced expression of podocyte differentiation markers and increased expression of VEGF and proliferation markers as compared to Tg26-SA/- mice. Primary podocytes isolated from Tg26-SA/+ mice showed increased Stat3 phosphorylation and reduced expression of podocyte differentiation markers. The tubulointerstitial compartment and isolated tubules of Tg26-SA/+ mice also had increased Stat3 phosphorylation and expression of Stat3 target genes. We confirmed that the expression of the HIV-1 transgene and reduction of Stat3 activity did not affect T and B cell development. In conclusion, Stat3 plays a critical role in the pathogenesis of HIVAN. C1 [He, John C.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Iyengar, Ravi; He, John C.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Xiong, Huabao; Ouyang, Xinshou] Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. [Feng, Xiaobei] Shanghai Jiao Tong Univ, Sch Med, RuiJin Hosp, Dept Nephrol, Shanghai 200030, Peoples R China. [Shen, Yuhong] Rockefeller Univ, Mol Cell Biol Lab, New York, NY 10021 USA. [Levy, David E.] NYU, Dept Pathol, New York, NY 10016 USA. [D'Agati, Vivette] Columbia Univ, Dept Pathol, New York, NY USA. [Lu, Ting-Chi; He, John C.] James J Peters VA Med Ctr, Bronx, NY USA. RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. EM cijiang.he@mssm.edu RI klotman, mary/A-1921-2016 FU NIH [R01 DK078897, P01 DK056492, R01 GM54508] FX J.C.H. is supported by NIH R01 DK078897. This work was also supported by NIH Grants P01 DK056492 to P.K. and R01 GM54508 to R.I. NR 44 TC 25 Z9 26 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2009 VL 20 IS 10 BP 2138 EP 2146 DI 10.1681/ASN.2008080879 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 510ST UT WOS:000271112700011 PM 19608706 ER PT J AU Chan, KE Lazarus, JM Thadhani, R Hakim, RM AF Chan, Kevin E. Lazarus, J. Michael Thadhani, Ravi Hakim, Raymond M. TI Warfarin Use Associates with Increased Risk for Stroke in Hemodialysis Patients with Atrial Fibrillation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ORAL ANTICOAGULANT-THERAPY; TRANSIENT ISCHEMIC ATTACK; STAGE RENAL-DISEASE; ADMINISTRATIVE DATA; THROMBOEMBOLIC COMPLICATIONS; VASCULAR EVENTS; ESRD PATIENTS; CO-MORBIDITY; PREVENTION; MORTALITY AB Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities. Here, we investigated the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort analysis of 1671 incident hemodialysis patients with preexisting atrial fibrillation. We followed patient outcomes from the time of initiation of dialysis for an average of 1.6 yr. Compared with nonuse, warfarin use associated with a significantly increased risk for new stroke (hazard ratio 1.93; 95% confidence interval 1.29 to 2.90); clopidogrel or aspirin use did not associate with increased risk for new stroke. Analysis using international normalized ratio (INR) suggested a dose-response relationship between the degree of anticoagulation and new stroke in patients on warfarin (P = 0.02 for trend). Warfarin users who received no INR monitoring in the first 90 d of dialysis had the highest risk for stroke compared with nonusers (hazard ratio 2.79; 95% confidence interval 1.65 to 4.70). Warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization. In conclusion, warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke. The risk is greatest in warfarin users who do not receive in-facility INR monitoring. C1 [Chan, Kevin E.; Lazarus, J. Michael; Hakim, Raymond M.] Fresenius Med Care NA, Waltham, MA 02451 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Chan, KE (reprint author), Fresenius Med Care NA, 920 Winter St, Waltham, MA 02451 USA. EM Kevin.chan@fmc-na.com NR 81 TC 183 Z9 192 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2009 VL 20 IS 10 BP 2223 EP 2233 DI 10.1681/ASN.2009030319 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 510ST UT WOS:000271112700020 PM 19713308 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI What is a Patient Navigator, and Should We Have Them in Major Cancer Centers? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2009 VL 7 IS 9 BP 905 EP 905 PG 1 WC Oncology SC Oncology GA 513PQ UT WOS:000271335700001 PM 19878636 ER PT J AU Anderson, KC Alsina, M Bensinger, W Biermann, S Chanan-Khan, A Cohen, AD Devine, S Djulbegovic, B Gasparetto, C Huff, CA Jagasia, M Medeiros, BC Meredith, R Raje, N Schriber, J Singhal, S Somlo, G Stockerl-Goldstein, K Tricot, G Vose, JM Weber, D Yahalom, J Yunus, F AF Anderson, Kenneth C. Alsina, Melissa Bensinger, William Biermann, Sybil Chanan-Khan, Asher Cohen, Adam D. Devine, Steven Djulbegovic, Benjamin Gasparetto, Cristina Huff, Carol Ann Jagasia, Madan Medeiros, Bruno C. Meredith, Ruby Raje, Noopur Schriber, Jeffrey Singhal, Seema Somlo, George Stockerl-Goldstein, Keith Tricot, Guido Vose, Julie M. Weber, Donna Yahalom, Joachim Yunus, Furhan TI Multiple Myeloma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE multiple myeloma; Waldenstrom's monoclonal protein; C-reactive protein; combination chemotherapy; stem cell transplant; primary amyloidosis; cytogenetics; proteasome inhibitor; immunomodulatory drugs; bisphosphonates; supportive therapies; novel therapies ID STEM-CELL TRANSPLANTATION; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY SYSTEMIC AMYLOIDOSIS; HIGH-DOSE DEXAMETHASONE; LENALIDOMIDE PLUS DEXAMETHASONE; PEGYLATED LIPOSOMAL DOXORUBICIN; RANDOMIZED CONTROLLED-TRIAL; DONOR LYMPHOCYTE INFUSIONS; NATIONAL-CANCER-INSTITUTE; NEWLY-DIAGNOSED MYELOMA C1 [Biermann, Sybil] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Chanan-Khan, Asher] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cohen, Adam D.] Roswell Pk Canc Inst, Buffalo, NY USA. [Devine, Steven] Fox Chase Canc Ctr, Philadelphia, PA USA. [Djulbegovic, Benjamin] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Jagasia, Madan] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Meredith, Ruby] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Raje, Noopur] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. [Schriber, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Somlo, George] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Tricot, Guido] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Tricot, Guido] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Vose, Julie M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Weber, Donna] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Yahalom, Joachim] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Yunus, Furhan] Mem Sloan Kettering Canc Ctr, New York, NY USA. Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. RI Cohen, Adam/F-6729-2012; Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 NR 128 TC 36 Z9 40 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2009 VL 7 IS 9 BP 908 EP 942 PG 35 WC Oncology SC Oncology GA 513PQ UT WOS:000271335700002 PM 19878637 ER PT J AU Laubach, JP Mitsiades, CS Mahindra, A Schlossman, RL Hideshima, T Chauhan, D Carreau, NA Ghobrial, IM Raje, N Munshi, NC Anderson, KC Richardson, PG AF Laubach, Jacob P. Mitsiades, Constantine S. Mahindra, Anuj Schlossman, Robert L. Hideshima, Teru Chauhan, Dharminder Carreau, Nicole A. Ghobrial, Irene M. Raje, Noopur Munshi, Nikhil C. Anderson, Kenneth C. Richardson, Paul G. TI Novel Therapies in the Treatment of Multiple Myeloma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE Multiple myeloma; cytogenetics; chemotherapy; thalidomide; lenalidomide; bortezomib ID STEM-CELL TRANSPLANTATION; PROTEASOME INHIBITOR PS-341; LENALIDOMIDE PLUS DEXAMETHASONE; COOPERATIVE-ONCOLOGY-GROUP; OVERCOMES DRUG-RESISTANCE; HIGH-DOSE DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; RANDOMIZED PHASE-III; EXTENDED FOLLOW-UP; VAD CHEMOTHERAPY AB Multiple myeloma (MM) is a clonal B-cell malignancy characterized by aberrant expansion of plasma cells within bone marrow and extramedullary sites. In 2009, 20,580 new cases of MM and 10,580 deaths from the disease occurred in the United States. Treatment traditionally consists of systemic chemotherapy, with adjunctive use of radiation or surgery in selected cases associated with extramedullary disease. The therapeutic landscape in MM has changed markedly in the past decade with the introduction of the novel immunomodulatory agents thalidomide and lenalidomide, and the first-in-class proteasome inhibitor bortezomib. Although MM remains an incurable malignancy, new approaches to therapy incorporating these agents have produced significantly higher response rates and improved intervals of both progression-free and overall survival in the context of randomized, controlled trials. In aggregate, the use of novel therapies in MM has been associated with substantial improvements in patient outcome. (JNCCN 2009;7:947-960) C1 [Laubach, Jacob P.; Mitsiades, Constantine S.; Schlossman, Robert L.; Hideshima, Teru; Chauhan, Dharminder; Carreau, Nicole A.; Ghobrial, Irene M.; Munshi, Nikhil C.; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mahindra, Anuj; Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol, Boston, MA USA. RP Laubach, JP (reprint author), Harvard Univ, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu NR 106 TC 28 Z9 28 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2009 VL 7 IS 9 BP 947 EP 960 PG 14 WC Oncology SC Oncology GA 513PQ UT WOS:000271335700003 PM 19878638 ER PT J AU Fok, JW Nogueira, R Singhal, AB AF Fok, J. W. Nogueira, R. Singhal, A. B. TI Cerebral angiographic features can distinguish reversible cerebral vasoconstriction syndromes (RCVS) from primary angiitis of the CNS (PACNS) SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 19th World Congress of Neurology CY OCT 24-30, 2009 CL Bangkok, THAILAND C1 [Fok, J. W.; Nogueira, R.; Singhal, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT PY 2009 VL 285 SU 1 BP S99 EP S100 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529ML UT WOS:000272521300346 ER PT J AU Posner, J AF Posner, J. TI Several treatment aspects regarding gliomas SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 19th World Congress of Neurology CY OCT 24-30, 2009 CL Bangkok, THAILAND C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Posner, J.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT PY 2009 VL 285 SU 1 BP S18 EP S18 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529ML UT WOS:000272521300063 ER PT J AU Putzki, N Kinkel, RP Dontchev, M Tanner, JP Kollman, C Simon, J O'Connor, P Hyde, R AF Putzki, N. Kinkel, R. P. Dontchev, M. Tanner, J. P. Kollman, C. Simon, J. O'Connor, P. Hyde, R. TI CHAMPIONS extension: 10-year outcomes in interferon beta-1a-treated patients at high risk for developing multiple sclerosis after a clinically isolated syndrome SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 19th World Congress of Neurology CY OCT 24-30, 2009 CL Bangkok, THAILAND C1 [Putzki, N.] Cantonal Hosp, St Gallen, Switzerland. [Putzki, N.] Univ Duisburg Essen, Dept Neurol, Essen, Germany. [Kinkel, R. P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Dontchev, M.; Tanner, J. P.; Kollman, C.] Hlth Res Fdn Inc, Jaeb Ctr, Tampa, FL USA. [Simon, J.] Portland VA Med Ctr, Portland, OR USA. [O'Connor, P.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Hyde, R.] Biogen Idec Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT PY 2009 VL 285 SU 1 BP S119 EP S120 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529ML UT WOS:000272521300412 ER PT J AU Singhal, AB Hajj-Ali, RA Calabrese, LH AF Singhal, A. B. Hajj-Ali, R. A. Calabrese, L. H. TI Reversible cerebral vasoconstriction syndromes (RCVS) - two center experience of 139 cases SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 19th World Congress of Neurology CY OCT 24-30, 2009 CL Bangkok, THAILAND C1 [Singhal, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hajj-Ali, R. A.; Calabrese, L. H.] Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT PY 2009 VL 285 SU 1 BP S100 EP S101 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529ML UT WOS:000272521300349 ER PT J AU De Luca, G Gibson, CM Bellandi, F Murphy, S Maioli, M Noc, M Zeymer, U Dudek, D Arntz, HR Zorman, S Gabriel, HM Emre, A Cutlip, D Rakowski, T Gyongyosi, M Huber, K van't Hof, A AF De Luca, Giuseppe Gibson, C. Michael Bellandi, Francesco Murphy, Sabina Maioli, Mauro Noc, Marko Zeymer, Uwe Dudek, Dariusz Arntz, Hans-Richard Zorman, Simona Gabriel, H. Mesquita Emre, Ayse Cutlip, Donald Rakowski, Tomasz Gyongyosi, Mariann Huber, Kurt van't Hof, Arnoud W. J. TI Benefits of pharmacological facilitation with glycoprotein IIb-IIIa inhibitors in diabetic patients undergoing primary angioplasty for STEMI. A subanalysis of the EGYPT cooperation SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; ST-SEGMENT RESOLUTION; RANDOMIZED CLINICAL-TRIALS; EMERGENCY-DEPARTMENT; REPERFUSION THERAPY; IIB/IIIA INHIBITORS; PILOT TRIAL; ABCIXIMAB; TIROFIBAN AB The Early Glycoprotein IIb-IIIa inhibitors in Primary angioplasty (EGYPT) cooperation aimed at evaluating, by pooling individual patient's data of randomized trials, the benefits of pharmacological facilitation with Gp IIb-IIIa inhibitors among STEMI patients undergoing primary angioplasty. In the current study we analyze the benefits of early Gp IIb-IIIa inhibitors in diabetic patients. The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. We examined all randomized trials on facilitation by early administration of Gp IIb-IIIa inhibitors in STEMI. No language restrictions were enforced. Individual patients' data were obtained from 11 out of 13 trials, including 1,662 patients. Diabetes was present in 281 (16.9%). Early Gp IIb-IIIa inhibitors were associated with improved preprocedural TIMI 3 flow (26.0% vs. 13.1%, P = 0.006), postprocedural TIMI 3 flow (90.1% vs. 75.0%, P = 0.18), MBG 3 (40.8% vs. 30.4%, P = 0.004), and less distal embolization (11.6% vs. 20.8%, P = 0.05). However, early Gp IIb-IIIa inhibitors did not significantly reduce mortality (8.3% vs. 9.5%, P = 0.64). This meta-analysis shows that pharmacological facilitation with early administration of Gp IIb-IIIa inhibitors in STEMI patients with diabetes undergoing primary angioplasty, is associated with significant benefits in terms of preprocedural and postprocedural TIMI flow, improved myocardial perfusion, without significant benefits in mortality. C1 [De Luca, Giuseppe] Eastern Piedmont Univ, Div Cardiol Maggiore Carita, Novara, Italy. [Gibson, C. Michael; Murphy, Sabina] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Bellandi, Francesco; Maioli, Mauro] Prato Hosp, Div Cardiol, Prato, Italy. [Noc, Marko; Zorman, Simona] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany. [Dudek, Dariusz; Rakowski, Tomasz] Jagiellonian Univ, Inst Cardiol, Dept Cardiol 2, Krakow, Poland. [Arntz, Hans-Richard] Charite, Med Klin 2, Berlin, Germany. [Gabriel, H. Mesquita] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal. [Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Instabul, Turkey. [Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA. [Gyongyosi, Mariann] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [Huber, Kurt] Wilhelminen Hosp, Dept Med Cardiol & Emergency Med 3, Vienna, Austria. [van't Hof, Arnoud W. J.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands. RP De Luca, G (reprint author), Eastern Piedmont Univ, Div Cardiol Maggiore Carita, Novara, Italy. EM giuseppe.deluca@maggioreosp.novara.it NR 45 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2009 VL 28 IS 3 BP 288 EP 298 DI 10.1007/s11239-008-0296-9 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 495AD UT WOS:000269860600008 PM 19030969 ER PT J AU Stein, PD Matta, F Yaekoub, AY Goodman, LR Sostman, HD Weg, JG Hales, CA Hull, RD Leeper, KV Beemath, A Saeed, IM Woodard, PK AF Stein, Paul D. Matta, Fadi Yaekoub, Abdo Y. Goodman, Lawrence R. Sostman, H. Dirk Weg, John G. Hales, Charles A. Hull, Russell D. Leeper, Kenneth V., Jr. Beemath, Afzal Saeed, Ibrahim M. Woodard, Pamela K. TI Reconstructed 4-chamber views compared with axial imaging for assessment of right ventricular enlargement on CT pulmonary angiograms SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Pulmonary embolism; Venous thromboembolism; Right ventricular enlargement; CT pulmonary angiography ID CHEST COMPUTED-TOMOGRAPHY; HELICAL CT; DYSFUNCTION SECONDARY; EMBOLISM; PREDICTORS; PROGNOSIS; MORTALITY AB Purpose To test the hypothesis that right enlargement assessed from right ventricular/left ventricular (RV/LV) dimension ratios of computed tomographic (CT) angiograms are equivalent irrespective of whether measured on axial views or reconstructed 4-chamber views. Methods RV/LV dimension ratios were calculated from measurements on axial views, manually reconstructed 4-chamber views and computer generated reconstructed 4-chamber views of CT angiograms in 152 patients with PE. Results Paired readings of the axial view and manually reconstructed 4-chamber view showed agreement with RV/LV a parts per thousand yen1 or RV/LV < 1 in 114 of 127 (89.8%). Paired readings also showed agreement in 119 of 127 (93.7%) with axial views and computer generated reconstructed 4-chamber views. The McNemar test showed no statistically significant difference between assessments of RV enlargement (RV/LV a parts per thousand yen 1) with any method. Conclusion Right ventricular enlargement can be determined from axial views on CT angiograms, which are readily and immediately available, without obtaining 4-chamber reconstructed views. C1 [Stein, Paul D.; Matta, Fadi; Yaekoub, Abdo Y.] St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI 48341 USA. [Stein, Paul D.] Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. [Goodman, Lawrence R.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Sostman, H. Dirk] Weill Cornell Med Coll, Off Dean, Houston, TX USA. [Sostman, H. Dirk] Methodist Hosp, Houston, TX 77030 USA. [Weg, John G.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Hales, Charles A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hales, Charles A.] Harvard Univ, Sch Med, Boston, MA USA. [Hull, Russell D.] Univ Calgary, Dept Med, Calgary, AB, Canada. [Leeper, Kenneth V., Jr.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Beemath, Afzal] Sinai Grace Hosp, Detroit, MI USA. [Saeed, Ibrahim M.; Woodard, Pamela K.] Washington Univ, Dept Radiol, St Louis, MO USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland Hosp, Dept Res, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org FU U.S. Department of Health and Human Services, Public Health Services, National Heart, Lung, and Blood Institute, Bethesda, Maryland [HL63899, HL63928, HL63931, HL63940, HL63981, HL63982, HL67453] FX This study was supported by Grants HL63899, HL63928, HL63931, HL63940, HL63981, HL63982, and HL67453 from the U. S. Department of Health and Human Services, Public Health Services, National Heart, Lung, and Blood Institute, Bethesda, Maryland. NR 17 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2009 VL 28 IS 3 BP 342 EP 347 DI 10.1007/s11239-009-0331-5 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 495AD UT WOS:000269860600016 PM 19326189 ER PT J AU Hebert, TL Wu, XY Yu, G Goh, BC Halvorsen, YDC Wang, Z Moro, C Gimble, JM AF Hebert, Teddi L. Wu, Xiying Yu, Gang Goh, Brian C. Halvorsen, Yuan-Di C. Wang, Zhong Moro, Cedric Gimble, Jeffrey M. TI Culture effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on cryopreserved human adipose-derived stromal/stem cell proliferation and adipogenesis SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Article DE adipogenesis; adipose-derived stem cells; edipermal growth factor; basic fibroblast growth factor; cryopreservation; differentiation ID MESENCHYMAL STEM-CELLS; HUMAN BONE-MARROW; EX-VIVO EXPANSION; GENE-EXPRESSION; HUMAN FAT; TISSUE; DIFFERENTIATION; CRYOPROTECTANT; MAINTENANCE; MECHANISMS AB Previous studies have demonstrated that EGF and bFGF maintain the stem cell properties of proliferating human adipose-derived stromal/stem cells (hASCs) in vitro. While the expansion and cryogenic preservation of isolated hASCs are routine, these manipulations can impact their proliferative and differentiation potential. This study examined cryogenically preserved hASCs (n = 4 donors), with respect to these functions, after culture with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) at varying concentrations (0-10 ng/ml). Relative to the control, cells supplemented with EGF and bFGF significantly increased proliferation by up to three-fold over 7-8 days. Furthermore, cryopreserved hASCs expanded in the presence of EGF and bFGF displayed increased oil red 0 staining following adipogenic induction. This was accompanied by significantly increased levels of several adipogenesis-related mRNAs: aP2, C/EBP alpha, lipoprotein lipase (LPL), PPAR gamma and PPAR gamma co-activator-1 (PGC1). Adipocytes derived from EGF- and bFGF-cultured hASCs exhibited more robust functionality based on insulin-stimulated glucose uptake and atriall natriuretic peptide (ANP)-stimulated lipolysis. These findings indicate that bFGF and EGF can be used as culture supplements to optimize the proliferative capacity of cryopreserved human ASCs and their adipogenic differentiation potential. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Hebert, Teddi L.; Wu, Xiying; Yu, Gang; Goh, Brian C.; Gimble, Jeffrey M.] Pennington Biomed Res Ctr, Stem Cell Biol Lab, Baton Rouge, LA 70808 USA. [Yu, Gang; Gimble, Jeffrey M.] Pennington Biomed Res Ctr, Clin Nutr Res Unit, Baton Rouge, LA 70808 USA. [Halvorsen, Yuan-Di C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Wang, Zhong] Pennington Biomed Res Ctr, Diabet & Nutr Lab, Baton Rouge, LA 70808 USA. [Moro, Cedric] Pennington Biomed Res Ctr, Endocrinol Lab, Baton Rouge, LA 70808 USA. RP Gimble, JM (reprint author), Pennington Biomed Res Ctr, Stem Cell Biol Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM gimblejm@pbrc.edu FU Pennington Biomedical Research Center; Pennington Biomedical Research Foundation; CNRU Center [1P30 DK072476]; NIDDK FX This work was supported in part by support (to J.M.G. and X.W.) from the Pennington Biomedical Research Center, Pennington Biomedical Research Foundation, and a CNRU Center Grant (No. 1P30 DK072476, to J.M.G and G.Y.) entitled 'Nutritional Programming: Environmental and Molecular Interactions', sponsored by NIDDK. The authors wish to thank Ms Laura Dallam for excellent editorial assistance. NR 44 TC 32 Z9 39 U1 1 U2 15 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1932-6254 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD OCT PY 2009 VL 3 IS 7 BP 553 EP 561 DI 10.1002/term.198 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA 506ZT UT WOS:000270819400007 PM 19670348 ER PT J AU Alam, HB Bice, LM Butt, MU Cho, SD Dubick, MA Duggan, M Englehart, MS Holcomb, JB Morris, MS Prince, MD Schreiber, MA Shults, C Sondeen, JL Tabbara, M Tieu, BH Underwood, SA AF Alam, Hasan B. Bice, Leticia M. Butt, Muhammad U. Cho, S. David Dubick, Michael A. Duggan, Michael Englehart, Michael S. Holcomb, John B. Morris, Melanie S. Prince, M. Dale Schreiber, Martin A. Shults, Christian Sondeen, Jill L. Tabbara, Malek Tieu, Brandon H. Underwood, Samantha A. CA Hemostatic Resuscitation Res Grp TI Testing of Blood Products in a Polytrauma Model: Results of a Multi-Institutional Randomized Preclinical Trial SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 24-27, 2008 CL Maui, HI SP Amer Assoc Surg Trauma DE Plasma; Hemorrhage; Shock; Coagulopathy; Liver injury; Polytrauma; Acidosis; Hypothermia ID FRESH-FROZEN PLASMA; ACUTE TRAUMATIC COAGULOPATHY; WHOLE-BLOOD; CELL TRANSFUSIONS; CUMULATIVE RISKS; RESUSCITATION; TEMPERATURE; MORTALITY; MILITARY; HYPOPERFUSION AB Introduction: Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model. Methods: Yorkshire swine (40 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3 x shed blood) + induction of hypother-mia (33 degrees C); (b) "Early hospital" phase = grade V liver injury; and (c) "Operative" phase = liver packing. After liver packing, the animals (n = 60) were randomized to the following groups: (1) Sham-instrumentation and anesthesia without hemorrhage/injuries, (2) fresh whole blood (FWB), (3) 6% hetastarch (Hextend), (4) fresh frozen plasma/packed RBCs in 1:1 ratio (1:1 FFP/PRBC), and (5) FFP alone. Treatment volumes were equal to the volume of shed blood. Hemodynamic and physiologic parameters and coagulation profile (thrombelastography, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelets) were monitored during the experiment and for 4 hours posttreatment. Results: At the end of prehospital phase, animals had developed significant acidosis (lactate >5 mmol/L and base deficit >9 mmol/L) and coagulopathy. Posttreatment mortality rates were 85% and 0% for the Hextend and blood component treated groups, respectively (p < 0.05). Hemodynamic parameters and survival rates were similar in groups that were treated with blood products (FWB, FFP, and FFP:PRBC). Animals treated with FFP and Hextend had significant anemia compared with the groups that received red blood cells (FWB and FFP:PRBC). Treatment with FFP and FFP:PRBC corrected the coagulopathy as effectively as FWB, whereas Hextend treatment worsened coagulopathy. Conclusions: In this reproducible model, we have shown that trauma-associated coagulopathy is made worse by hetastarch, but it can be rapidly reversed with the administration of blood components. Impressively, infusion of FFP, even without any red blood cells, can correct the coagulopathy and result in excellent early survival. C1 [Alam, Hasan B.; Butt, Muhammad U.; Duggan, Michael; Shults, Christian; Tabbara, Malek] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma, Boston, MA USA. [Bice, Leticia M.; Dubick, Michael A.; Holcomb, John B.; Prince, M. Dale; Sondeen, Jill L.] USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [Cho, S. David; Englehart, Michael S.; Morris, Melanie S.; Schreiber, Martin A.; Tieu, Brandon H.; Underwood, Samantha A.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org OI Tabbara, Malek/0000-0003-1046-7803 NR 38 TC 39 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2009 VL 67 IS 4 BP 856 EP 864 DI 10.1097/TA.0b013e3181b5ae75 PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 506BE UT WOS:000270747000029 PM 19820596 ER PT J AU Resick, PA Miller, MW AF Resick, Patricia A. Miller, Mark W. TI Posttraumatic Stress Disorder: Anxiety or Traumatic Stress Disorder? SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 2008 CL Chicago, IL SP Int Soc Traumat Stress Studies ID COMMON MENTAL-DISORDERS; VIETNAM COMBAT VETERANS; DEFICIT HYPERACTIVITY DISORDER; ADMINISTERED PTSD SCALE; FEMALE CRIME VICTIMS; DSM-IV; PSYCHOPHYSIOLOGICAL ASSESSMENT; INTERNALIZING SUBTYPES; CONDUCT DISORDER; VIOLENT CRIME AB The authors examine the question of whether posttraumatic stress disorder (PTSD) should continue to he classified with the anxiety disorders in the upcoming revision of the Diaenostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V; American Psychiatric Association) classification system. They examine four areas of research that challenge the placement of PTSD among the anxiety disorders: research on peritraumatic emotions and their association with later PTSD symptoms, the role of emotions over the course of PTSD, physiological reactivity and emotional responses, and comorbidity patterns. The authors conclude with the recommendation that PTSD he included among a new category of traumatic stress disorders in DSM-V C1 [Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM Patricia.Resick@va.gov; Mark.Miller5@va.gov RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 FU CSRD VA [I01 CX000431] NR 57 TC 41 Z9 41 U1 6 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2009 VL 22 IS 5 BP 384 EP 390 DI 10.1002/jts.20437 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 515SK UT WOS:000271493000006 PM 19774665 ER PT J AU Shin, LM Handwerger, K AF Shin, Lisa M. Handwerger, Kathryn TI Is Posttraumatic Stress Disorder A Stress-Induced Fear Circuitry Disorder? SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 2008 CL Chicago, IL SP Int Soc Traumat Stress Studies ID MEDIAL PREFRONTAL CORTEX; CHILDHOOD SEXUAL-ABUSE; CEREBRAL-BLOOD-FLOW; SCRIPT-DRIVEN IMAGERY; ANTERIOR CINGULATE FUNCTION; COGNITIVE-BEHAVIOR THERAPY; HIPPOCAMPAL FUNCTION; SYMPTOM PROVOCATION; DECLARATIVE MEMORY; TRAUMATIC MEMORIES AB Neuroimaging studies of posttraumatic stress disorder (PTSD) have reported functional abnormalities in brain regions involved in fear conditioning, extinction, and emotion regulation. These findings have prompted researchers to consider whether PTSD can be characterized as a stress-induced fear circuitry disorder. In this review, the authors summarize the results of functional neuroimaging studies and conclude that there is a strong argument for characterizing PTSD as a stress-induced fear circuitry disorder. They also acknowledge that (a) fear is not the only emotion associated with PTSD, (b) a state of fear is not required to observe fear-circuitry abnormalities in this disorder, and (c) not all functional abnormalities in PTSD are related to fear circuitry. Implications for future diagnostic classifications are discussed. C1 [Shin, Lisa M.; Handwerger, Kathryn] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Shin, Lisa M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM lisa.shin@tufts.edu NR 83 TC 38 Z9 39 U1 3 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2009 VL 22 IS 5 BP 409 EP 415 DI 10.1002/jts.20442 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 515SK UT WOS:000271493000009 PM 19743481 ER PT J AU Yehuda, R Bierer, LA AF Yehuda, Rachel Bierer, Linda A. TI The Relevance of Epigenetics to PTSD: Implications for the DSM-V SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 2008 CL Chicago, IL SP Int Soc Traumat Stress Studies ID POSTTRAUMATIC-STRESS-DISORDER; MATERNAL-CARE; ANIMAL-MODEL; HOLOCAUST SURVIVORS; GLUCOCORTICOID-RECEPTOR; CHILDHOOD ABUSE; RISK-FACTORS; RESPONSES; GENE; CORTISOL AB Epigenetic modifications, such as DNA methylation, can occur in response to environmental influences to alter the functional expression of genes in an enduring and potentially, intergenerationally transmissible manner. As such, they may explain interindividual variation, as well as the long-lasting effects of trauma exposure. Although there are currently no findings that suggest epigenetic modifications that are specific to posttraumatic stress disorder (PTSD) or PTSD risk, many recent observations are compatible with epigenetic explanations. These include recent findings of stress-related gene expression, in utero contributions to infant biology, the association of PTSD risk with maternal PTSD, and the relevance of childhood adversity to the development of PTSD. The relevance of epigenetic mechanisms to formulations of PTSD for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is described. C1 James J Peters VAMC, PTSD Clin & Res Program, Bronx, NY USA. Mt Sinai Sch Med, Traumat Stress Studies Div, New York, NY USA. RP Yehuda, R (reprint author), Bronx VA OOMH, 116-A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@va.gov FU NCRR NIH HHS [M01 RR000071-430595, M01 RR000071, M01 RR000071-447234, M01 RR000071-458256]; NIMH NIH HHS [R56 MH077321, R56 MH077321-01] NR 57 TC 73 Z9 76 U1 9 U2 28 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2009 VL 22 IS 5 BP 427 EP 434 DI 10.1002/jts.20448 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 515SK UT WOS:000271493000011 PM 19813242 ER PT J AU Maguen, S Metzler, TJ Litz, BT Seal, KH Knight, SJ Marmar, CR AF Maguen, Shira Metzler, Thomas J. Litz, Brett T. Seal, Karen H. Knight, Sara J. Marmar, Charles R. TI The Impact of Killing in War on Mental Health Symptoms and Related Functioning SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 2008 CL Chicago, IL SP Int Soc Traumat Stress Studies ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; COMBAT VETERANS; ZONE STRESSORS; VIOLENCE; PREVALENCE; EXPOSURE; FEMALE; MMPI-2; SCALE AB This study examined the mental health and functional consequences associated with killing combatants and noncombatants. Using the National Vietnam Veterans Readjustment Study (NVVRS) survey data, the authors reported the percentage of male Vietnam theater veterans (N = 1200) who killed an enemy combatant, civilian, and/or prisoner of war. They next examined the relationship between killing in war and a number Of mental health and functional outcomes using the clinical interview subsample of the NVVRS (n = 259). Controlling for demographic variables and exposure to general combat experiences, the authors found that killing was associated with posttraumatic stress disorder symptoms, dissociation, functional impairment, and violent behaviors. Experiences of killing in war are important to address in the evaluation and treatment of veterans. C1 [Maguen, Shira] Univ Calif San Francisco, PTSD Program 116 P, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Litz, Brett T.] Boston Univ, Sch Med, Natl Ctr PTSD,Massachusetts Vet Epidemiol Res & I, Dept Vet Affairs Boston Healthcare Syst, Boston, MA 02215 USA. [Maguen, Shira; Knight, Sara J.; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Litz, Brett T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Maguen, S (reprint author), Univ Calif San Francisco, PTSD Program 116 P, San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94143 USA. EM Shira.Maguen@va.gov NR 28 TC 41 Z9 42 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2009 VL 22 IS 5 BP 435 EP 443 DI 10.1002/jts.20451 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 515SK UT WOS:000271493000012 PM 19842160 ER PT J AU McDougal, WS AF McDougal, W. Scott TI Tumor Size is a Determinant of the Rate of Stage T1 Renal Cell Cancer Synchronous Metastasis COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02163 USA. RP McDougal, WS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02163 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2009 VL 182 IS 4 BP 1293 EP 1293 DI 10.1016/j.juro.2009.06.116 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 493UP UT WOS:000269764100013 PM 19683301 ER PT J AU Chaikof, EL Brewster, DC Dalman, RL Makaroun, MS Illig, KA Sicard, GA Timaran, CH Upchurch, GR Veith, FJ AF Chaikof, Elliot L. Brewster, David C. Dalman, Ronald L. Makaroun, Michel S. Illig, Karl A. Sicard, Gregorio A. Timaran, Carlos H. Upchurch, Gilbert R., Jr. Veith, Frank J. TI The care of patients with an abdominal aortic aneurysm: The Society for Vascular Surgery practice guidelines SO JOURNAL OF VASCULAR SURGERY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; INTERNAL ILIAC ARTERY; OBSTRUCTIVE PULMONARY-DISEASE; OPEN SURGICAL REPAIR; HIGH-RISK PATIENTS; CONTRAST-INDUCED NEPHROPATHY; ENDOVASCULAR STENT-GRAFT; COLOR DUPLEX ULTRASOUND; DEEP VENOUS THROMBOSIS; INTERMEDIATE FOLLOW-UP C1 [Chaikof, Elliot L.] Emory Univ, Dept Surg, Atlanta, GA 30322 USA. [Brewster, David C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dalman, Ronald L.] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. [Makaroun, Michel S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA. [Illig, Karl A.] Univ Rochester, Dept Surg, Rochester, NY 14627 USA. [Sicard, Gregorio A.] Washington Univ, Dept Surg, St Louis, MO 63130 USA. [Timaran, Carlos H.] Univ Texas SW, Dept Surg, Dallas, TX USA. [Upchurch, Gilbert R., Jr.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Veith, Frank J.] Cleveland Clin Fdn, Dept Vasc Surg, Cleveland, OH 44195 USA. RP Chaikof, EL (reprint author), Emory Univ, Dept Surg, 101 Woodruff Circle,Rm 5105, Atlanta, GA 30322 USA. EM echaiko@emory.edu NR 511 TC 270 Z9 275 U1 3 U2 18 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2009 VL 50 SU S BP 2S EP 49S DI 10.1016/j.jvs.2009.07.002 PG 48 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 501TG UT WOS:000270404600002 PM 19786250 ER PT J AU Conrad, MF Kang, JW Cambria, RP Brewster, DC Watkins, MT Kwolek, CJ LaMuraglia, GM AF Conrad, Mark F. Kang, Jeanwan Cambria, Richard P. Brewster, David C. Watkins, Michael T. Kwolek, Christopher J. LaMuraglia, Glenn M. TI Infrapopliteal balloon angioplasty for the treatment of chronic occlusive disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CRITICAL LIMB ISCHEMIA; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; LOWER-EXTREMITY REVASCULARIZATION; TIBIAL VESSEL OCCLUSIONS; INFRAINGUINAL BYPASS; SUBINTIMAL ANGIOPLASTY; RESULTS JUSTIFY; BARE STENTS; SALVAGE; ARTERIES AB Objective: There is little documentation of the effectiveness of percutaneous balloon angioplasty (PTA) of infrapopliteal vessels for the treatment of chronic lower extremity ischemia. This stud), reviewed our recent experience with infrapopliteal PTA in a large series of patients to determine its effectiveness as a treatment modality. Methods: All patients undergoing primary infrapopliteal PTA from March 2002 to June 2006 were included. Primary study end points were primary patency, assisted patency, limb salvage, and patient survival assessed by Kaplan-Meier life-table analysis. Factors predictive of PTA failure and patient longevity were evaluated by multivariate methods. Results: There were 155 PTAs undertaken in 144 patients (70% men; mean age, 74 years), with critical limb ischemia (86%), diabetes (66%), and renal insufficiency (45%). Infrapopliteal lesions were classified as TransAtlantic Inter-Society Consensus A (7%), B (18%), C (39%), and D (35%). PTA was confined to the infrapopliteal segment in 40 (26%), and 115 (74%) underwent multilevel treatment. Five patients (3%) received stents. Technical success was 95%. The 30-day mortality was 2%, and major morbidity was 3%. The mean follow-up was 22 months (range, 0-54 months). The 40-month actuarial primary patency was 62% (standard error, 5%), with assisted patency (infrapopliteal re-PTA, 25 [16%]) of 90%. Interval conversion to bypass surgery occurred in seven (5%). Nonhealing ulcers occurred in 118 patients (76%), of which 76 (64%) healed during follow-up. Of the 42 unhealed ulcers, 15 (13%) required major amputations for a 40-month limb salvage of 86.2%. Multivariate predictors that were negative for primary patency included 0/1 vessel runoff (P = .01), critical limb ischemia (P = .002), and dialysis (P = .03). Negative predictors of limb salvage included dialysis (P = .007) and failure to improve runoff to the foot (P = .006). At 40-months, patient survival was 54%, with negative predictors including severe pulmonary disease (P = .01), coronary artery disease (P = .04), and renal insufficiency (P < .001). Conclusions: Infrapopliteal angioplasty can be performed safely with favorable results in patients with limited longevity. Primary patency is related to disease extent. Secondary interventions may be necessary to maintain clinical success. These data indicate that PTA should be considered as initial therapy for infrapopliteal occlusive disease in patients with lower extremity ischemia. (J Vasc Surg 2009;50:799-805.) C1 Massachusetts Gen Hosp, Gen Surg Serv, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Conrad, MF (reprint author), 15 Parkman St,WAC 4, Boston, MA 02114 USA. EM mconrad@partners.org NR 34 TC 56 Z9 68 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2009 VL 50 IS 4 BP 799 EP 805 DI 10.1016/j.jvs.2009.05.026 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 501TF UT WOS:000270404500013 PM 19786239 ER PT J AU Chaikof, EL Brewster, DC Dalman, RL Makaroun, MS Illig, KA Sicard, GA Timaran, CH Upchurch, GR Veith, FJ AF Chaikof, Elliot L. Brewster, David C. Dalman, Ronald L. Makaroun, Michel S. Illig, Karl A. Sicard, Gregorio A. Timaran, Carlos H. Upchurch, Gilbert R., Jr. Veith, Frank J. TI SVS practice guidelines for the care of patients with an abdominal aortic aneurysm: Executive summary SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HYPOGASTRIC ARTERY INTERRUPTION; US MULTICENTER TRIAL; ENDOVASCULAR REPAIR; COMPUTED-TOMOGRAPHY; CLINICAL-TRIAL; VENOUS THROMBOSIS; VASCULAR-SURGERY; RISK-FACTORS; FOLLOW-UP C1 [Chaikof, Elliot L.] Emory Univ, Dept Surg, Atlanta, GA 30322 USA. [Brewster, David C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dalman, Ronald L.] Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA. [Makaroun, Michel S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Illig, Karl A.] Univ Rochester, Dept Surg, Rochester, NY USA. [Sicard, Gregorio A.] Washington Univ, Dept Surg, St Louis, MO USA. [Timaran, Carlos H.] Univ Texas SW, Dept Surg, Dallas, TX USA. [Upchurch, Gilbert R., Jr.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Veith, Frank J.] Cleveland Clin Fdn, Dept Vasc Surg, Cleveland, OH 44195 USA. RP Chaikof, EL (reprint author), Emory Univ, Dept Surg, 101 Woodruff Circle,Rm 5105, Atlanta, GA 30322 USA. EM echaiko@emory.edu NR 67 TC 112 Z9 113 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2009 VL 50 IS 4 BP 880 EP 896 DI 10.1016/j.jvs.2009.07.001 PG 17 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 501TF UT WOS:000270404500024 PM 19786241 ER PT J AU Etemad, B Fellows, A Kwambana, B Kamat, A Feng, Y Lee, S Sagar, M AF Etemad, Behzad Fellows, Angela Kwambana, Brenda Kamat, Anupa Feng, Yang Lee, Sandra Sagar, Manish TI Human Immunodeficiency Virus Type 1 V1-to-V5 Envelope Variants from the Chronic Phase of Infection Use CCR5 and Fuse More Efficiently than Those from Early after Infection SO JOURNAL OF VIROLOGY LA English DT Article ID ENTRY INHIBITOR SENSITIVITY; DYNAMICS IN-VIVO; MACROPHAGE-TROPISM; HIV-1 INFECTION; SEQUENCE VARIATION; CORECEPTOR USAGE; ANTIBODY NEUTRALIZATION; GASTROINTESTINAL-TRACT; REPLICATION-COMPETENT; BIOLOGICAL-PROPERTIES AB Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein modifications over the course of infection have been associated with coreceptor switching and antibody neutralization resistance, but the effect of the changes on replication and host cell receptor usage remains unclear. To examine this question, unique early-and chronic-stage infection envelope V1-toV5 (V1-V5) segments from eight HIV-1 subtype A-infected subjects were incorporated into an isogenic background to construct replication-competent recombinant viruses. In all subjects, viruses with chronic-infection V1-V5 segments showed greater replication capacity than those with early-infection V1-V5 domains in cell lines with high levels of both the CD4 and the CCR5 receptors. Viruses with chronic-infection V1-V5s demonstrated a significantly increased ability to replicate in cells with low CCR5 receptor levels and greater resistance to CCR5 receptor and fusion inhibitors compared to those with early-infection V1-V5 segments. These properties were associated with sequence changes in the envelope V1-V3 segments. Viruses with the envelope segments from the two infection time points showed no significant difference in their ability to infect cells with low CD4 receptor densities, in their sensitivity to soluble CD4, or in their replication capacity in monocyte-derived macrophages. Our results suggest that envelope changes, primarily in the V1-V3 domains, increase both the ability to use the CCR5 receptor and fusion kinetics. Thus, envelope modifications over time within a host potentially enhance replication capacity. C1 [Etemad, Behzad; Fellows, Angela; Kwambana, Brenda; Kamat, Anupa; Sagar, Manish] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Cambridge, MA 02139 USA. [Feng, Yang; Lee, Sandra] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Feng, Yang; Lee, Sandra] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Sagar, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 65 Landsdowne St,Room 447, Cambridge, MA 02139 USA. EM msagar@partners.org OI Sagar, Manish/0000-0001-9803-6594 FU NIH [AI1077473]; American Foundation for AIDS Research ( amfAR); Doris Duke Charitable Foundation FX This study was supported by NIH grant AI1077473 ( M. S.), the American Foundation for AIDS Research ( amfAR) ( M. S.), and a Doris Duke Charitable Foundation Early Career Development Award ( M. S.). NR 88 TC 27 Z9 27 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2009 VL 83 IS 19 BP 9694 EP 9708 DI 10.1128/JVI.00925-09 PG 15 WC Virology SC Virology GA 491WX UT WOS:000269614300008 PM 19625411 ER PT J AU Thobakgale, CF Prendergast, A Crawford, H Mkhwanazi, N Ramduth, D Reddy, S Molina, C Mncube, Z Leslie, A Prado, J Chonco, F Mphatshwe, W Tudor-Williams, G Jeena, P Blanckenberg, N Dong, K Kiepiela, P Coovadia, H Ndung'u, T Walker, BD Goulder, PJR AF Thobakgale, Christina F. Prendergast, Andrew Crawford, Hayley Mkhwanazi, Nompumelelo Ramduth, Danni Reddy, Sharon Molina, Claudia Mncube, Zenele Leslie, Alasdair Prado, Julia Chonco, Fundi Mphatshwe, Wendy Tudor-Williams, Gareth Jeena, Prakash Blanckenberg, Natasha Dong, Krista Kiepiela, Photini Coovadia, Hoosen Ndung'u, Thumbi Walker, Bruce D. Goulder, Philip J. R. TI Impact of HLA in Mother and Child on Disease Progression of Pediatric Human Immunodeficiency Virus Type 1 Infection SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE ESCAPE; HIV-INFECTION; CTL ESCAPE; CLASS-I; RANDOMIZED-TRIAL; AFRICAN INFANTS; VIRAL LOAD; TRANSMISSION; GAG; MUTATIONS AB A broad Gag-specific CD8(+) T-cell response is associated with effective control of adult human immunodeficiency virus (HIV) infection. The association of certain HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune control is linked to mutations within Gag epitopes presented by these alleles that allow HIV to evade the immune response but that also reduce viral replicative capacity. Transmission of such viruses containing mutations within Gag epitopes results in lower viral loads in adult recipients. In this study of pediatric infection, we tested the hypothesis that children may tend to progress relatively slowly if either they themselves possess one of the protective HLA-B alleles or the mother possesses one of these alleles, thereby transmitting a low-fitness virus to the child. We analyzed HLA type, CD8(+) T-cell responses, and viral sequence changes for 61 mother-child pairs from Durban, South Africa, who were monitored from birth. Slow progression was significantly associated with the mother or child possessing one of the protective HLA-B alleles, and more significantly so when the protective allele was not shared by mother and child (P = 0.007). Slow progressors tended to make CD8(+) T-cell responses to Gag epitopes presented by the protective HLA-B alleles, in contrast to progressors expressing the same alleles (P = 0.07; Fisher's exact test). Mothers expressing the protective alleles were significantly more likely to transmit escape variants within the Gag epitopes presented by those alleles than mothers not expressing those alleles (75% versus 21%; P = 0.001). Reversion of transmitted escape mutations was observed in all slow-progressing children whose mothers possessed protective HLA-B alleles. These data show that HLA class I alleles influence disease progression in pediatric as well as adult infection, both as a result of the CD8(+) T-cell responses generated in the child and through the transmission of low-fitness viruses by the mother. C1 [Thobakgale, Christina F.; Mkhwanazi, Nompumelelo; Ramduth, Danni; Reddy, Sharon; Mncube, Zenele; Chonco, Fundi; Mphatshwe, Wendy; Jeena, Prakash; Blanckenberg, Natasha; Dong, Krista; Kiepiela, Photini; Coovadia, Hoosen; Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Prendergast, Andrew; Crawford, Hayley; Molina, Claudia; Leslie, Alasdair; Prado, Julia; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. [Walker, Bruce D.] Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA. [Tudor-Williams, Gareth] Univ London Imperial Coll Sci Technol & Med, Dept Paediat, Div Med, London, England. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Thobakgale, CF (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. EM Thobakgalec@ukzn.ac.za OI Ndung'u, Thumbi/0000-0003-2962-3992 FU Doris Duke Charitable Foundation [20011031]; The Wellcome Trust; Bristol Myers Squibb Secure the Future [RES116/01] FX This study was funded by the Doris Duke Charitable Foundation ( grant 20011031 to P. J. R. G.), The Wellcome Trust ( to P. J. R. G.), and Bristol Myers Squibb Secure the Future ( grant RES116/01 to P. J. R. G.). T. N.holds the South African DST/NRF Chair in Systems Biology of HIV/AIDS. NR 34 TC 33 Z9 34 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2009 VL 83 IS 19 BP 10234 EP 10244 DI 10.1128/JVI.00921-09 PG 11 WC Virology SC Virology GA 491WX UT WOS:000269614300054 PM 19605475 ER PT J AU Holsen, LM Spaeth, SB Ogden, LA Lee, JH Klibanski, A Whitfield-Gabrieli, S Goldstein, JM AF Holsen, Laura M. Spaeth, Sarah B. Ogden, Lauren A. Lee, Jong-Hwan Klibanski, Anne Whitfield-Gabrieli, Susan Goldstein, Jill M. TI Stress-Response Circuitry Hypoactivity and Hormonal Dysregulation in Women with Depression SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Holsen, Laura M.; Spaeth, Sarah B.; Ogden, Lauren A.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Lee, Jong-Hwan] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Goldstein, Jill M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Holsen, Laura M.; Lee, Jong-Hwan; Klibanski, Anne; Goldstein, Jill M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2009 VL 18 IS 10 BP 1498 EP 1498 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 512FJ UT WOS:000271231200029 ER PT J AU Isakova, T Gutierrez, OM Wolf, M AF Isakova, Tamara Gutierrez, Orlando M. Wolf, Myles TI A blueprint for randomized trials targeting phosphorus metabolism in chronic kidney disease SO KIDNEY INTERNATIONAL LA English DT Review DE cardiovascular disease; chronic kidney disease; clinical trials; FGF23; phosphorus ID STAGE RENAL-DISEASE; FIBROBLAST GROWTH FACTOR-23; LEFT-VENTRICULAR HYPERTROPHY; CORONARY-ARTERY CALCIFICATION; DOMINANT HYPOPHOSPHATEMIC RICKETS; VITAMIN-D METABOLISM; PULSE-WAVE VELOCITY; HEMODIALYSIS-PATIENTS; CARDIOVASCULAR-DISEASE; VASCULAR CALCIFICATION AB The diagnosis of chronic kidney disease (CKD) confers dismal clinical outcomes regardless of whether patients are initiating dialysis and face a median survival of only 2-3 years or they have earlier-stage CKD and face a risk of death that is greater than the risk of progression to dialysis. These poor outcomes are driven by extraordinarily high rates of cardiovascular disease that historically have not responded to risk-factor modification strategies proven to attenuate risk in the general population. Nor have measures aimed at increasing the dose or quality of dialysis made an appreciable dent in mortality. Still worse, interventions that were expected to be beneficial resulted in increased mortality in recent trials. Although this apparent lack of progress in advancing the care of CKD is discouraging, resignation is not an option. On the contrary, with the rising rates of CKD worldwide, there is an urgent need to rigorously test novel therapeutic strategies in randomized trials. The breadth of accumulating evidence linking disordered phosphorus metabolism to adverse outcomes spans in vitro, animal, and human studies, and positions phosphorus management as an attractive target for intervention. Although opinion-based practice guidelines promote phosphorus management strategies that are widely accepted in dialysis patients, there is a clear need to perform randomized controlled trials to prove or disprove the benefits of therapy. Perhaps even more important, the discovery of fibroblast growth factor 23 (FGF23) and its potential as a novel diagnostic to identify disordered phosphorus metabolism at an early, subclinical state has presented the opportunity to develop placebo-controlled randomized trials in pre-dialysis CKD patients with normal serum phosphate levels. This commentary considers the justification and challenges for such trials and presents a 'first-draft' blueprint of distinct trial approaches to initiate a dialog that will ultimately culminate in studies aimed at improving survival across the spectrum of CKD. Kidney International (2009) 76, 705-716; doi: 10.1038/ki.2009.246; published online 15 July 2009 C1 [Gutierrez, Orlando M.; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [Isakova, Tamara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit,Dept Med, Boston, MA USA. RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, 1120 NW 14th St, Miami, FL 33136 USA. EM mwolf2@med.miami.edu FU American Kidney Fund Clinical Scientist in Nephrology; National Institutes of Health [K23DK081673, RO1DK076116, R01DK081374] FX This study was supported by grants from the American Kidney Fund Clinical Scientist in Nephrology Fellowship (TI), and grants K23DK081673 (OMG), RO1DK076116 (MW), and R01DK081374 (MW) from the National Institutes of Health. NR 157 TC 63 Z9 66 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2009 VL 76 IS 7 BP 705 EP 716 DI 10.1038/ki.2009.246 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 494NC UT WOS:000269819100006 PM 19606082 ER PT J AU Je, YJ Schutz, FAB Choueiri, TK AF Je, Youjin Schutz, Fabio A. B. Choueiri, Toni K. TI Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials SO LANCET ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; PHASE-II TRIAL; ADVANCED HEPATOCELLULAR-CARCINOMA; ANTI-VEGF THERAPY; TARGETED THERAPY; LUNG-CANCER; OPEN-LABEL; BEVACIZUMAB; ANGIOGENESIS; TUMORS AB Background Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors used in various cancers. Bleeding has been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to calculate the incidence and relative risk associated with use of sunitinib and sorafenib. Methods We searched PubMed (from January, 1966, to April, 2009) and meeting proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology (2004-09) for relevant clinical trials. Eligible studies included phase 2 and 3 trials and expanded-access programmes. Statistical analyses were done to calculate summary incidences, relative risks, and 95% CI, using random-effects or fixed-effects models based on the heterogeneity of included studies. Findings 23 trials were selected for the meta-analysis, yielding a total of 6779 patients. The incidence of bleeding events (all grades) was 16.7% (95% CI 12.7-21.5), and that of high-grade events was 2.4% (1.6-3.9). The relative risk of all-grade bleeding events associated with sunitinib and sorafenib (for randomised controlled trials only) was 2.0 (1.14-3.49; p=0.015). Our analysis was also stratified by underlying malignant disease (renal-cell carcinoma vs non-renal-cell carcinoma) and agent used, but no differences were recorded. Interpretation Treatment with the VEGFR tyrosine-kinase inhibitors sunitinib and sorafenib is associated with a significant increase in risk of bleeding. C1 [Choueiri, Toni K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu NR 48 TC 130 Z9 132 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2009 VL 10 IS 10 BP 967 EP 974 DI 10.1016/S1470-2045(09)70222-0 PG 8 WC Oncology SC Oncology GA 508LL UT WOS:000270932800015 PM 19767240 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Survival Impact of Treatment Options for Papillary Microcarcinoma of the Thyroid SO LARYNGOSCOPE LA English DT Article DE Papillary thyroid microcarcinoma; cancer; survival impact; radioactive iodine therapy; thyroidectomy ID LYMPH-NODE METASTASIS; PROGNOSTIC-FACTORS; CARCINOMA; EXPERIENCE; MANAGEMENT; CANCER AB Objectives/Hypothesis: Evaluate the impact of medical and surgical interventions on the survival of patients with papillary microcarcinoma (PMC) of the thyroid, a common tumor with an increasing worldwide incidence. Study Design: Cross-sectional population analysis of a prospectively maintained database. Methods: Cases of nonmetastatic PMC treated with cancer-directed surgery with or without postoperative radioactive iodine (RAI) therapy were extracted from the Surveillance, Epidemiology and End Results Database (1988-2005). Kaplan-Meier disease-specific survival (DSS) and overall survivals were compared according to extent of thyroidectomy and use of RAI therapy. Cox regression analysis was performed to determine the influence of these factors on survival. Results: A total of 7,818 cases of PMC were identified. Overall actuarial survival rates at 10 and 15 years were 96.6% and 96.3%, respectively. DSS was 99.9% at both time intervals, with a total of 10 thyroid cancer-related deaths. There were no significant differences in DSS for patients who underwent total thyroidectomy, near-total/subtotal thyroidectomy, or lobectomy (P = .239). DSS for patients receiving RAI therapy was not significantly different than that of patients who did not (P = .504). On multivariate analysis, only increasing age at diagnosis, successfully predicted poor DSS (P = .001), whereas gender (P = .481), use of RAI therapy (P = .633), and extent of thyroidectomy (P = .104) did not. Conclusions: PMC carries an excellent prognosis with respect to both overall and disease-specific survival that is independent of surgical extent and the use of RAI therapy. An isolated, fine-needle-aspiration proven unilateral PMC focus in a patient lacking evidence of metastatic disease may be treated with lobectomy alone. C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Lin, Harrison W.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 20 TC 28 Z9 30 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2009 VL 119 IS 10 BP 1983 EP 1987 DI 10.1002/lary.20617 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 502YW UT WOS:000270498100019 PM 19655332 ER PT J AU Palumbo, A Sezer, O Kyle, R Miguel, JS Orlowski, RZ Moreau, P Niesvizky, R Morgan, G Comenzo, R Sonneveld, P Kumar, S Hajek, R Giralt, S Bringhen, S Anderson, KC Richardson, PG Cavo, M Davies, F Blade, J Einsele, H Dimopoulos, MA Spencer, A Dispenzieri, A Reiman, T Shimizu, K Lee, JH Attal, M Boccadoro, M Mateos, M Chen, W Ludwig, H Joshua, D Chim, J Hungria, V Turesson, I Durie, BGM Lonial, S AF Palumbo, A. Sezer, O. Kyle, R. Miguel, J. S. Orlowski, R. Z. Moreau, P. Niesvizky, R. Morgan, G. Comenzo, R. Sonneveld, P. Kumar, S. Hajek, R. Giralt, S. Bringhen, S. Anderson, K. C. Richardson, P. G. Cavo, M. Davies, F. Blade, J. Einsele, H. Dimopoulos, M. A. Spencer, A. Dispenzieri, A. Reiman, T. Shimizu, K. Lee, J. H. Attal, M. Boccadoro, M. Mateos, M. Chen, W. Ludwig, H. Joshua, D. Chim, J. Hungria, V. Turesson, I. Durie, B. G. M. Lonial, S. CA IMWG TI International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation SO LEUKEMIA LA English DT Review DE myeloma; guidelines; treatment; chemotherapy ID PEGYLATED LIPOSOMAL DOXORUBICIN; LENALIDOMIDE PLUS DEXAMETHASONE; RANDOMIZED CONTROLLED-TRIAL; NEWLY-DIAGNOSED MYELOMA; ELDERLY-PATIENTS; STAGING SYSTEM; ORAL CYCLOPHOSPHAMIDE; PULSED DEXAMETHASONE; MAINTENANCE THERAPY; COMBINATION THERAPY AB In 2005, the first guidelines were published on the management of patients with multiple myeloma (MM). An expert panel reviewed the currently available literature as the basis for a set of revised and updated consensus guidelines for the diagnosis and management of patients with MM who are not eligible for autologous stem cell transplantation. Here we present recommendations on the diagnosis, treatment of newly diagnosed non-transplant-eligible patients and the management of complications occurring during induction therapy among these patients. These guidelines will aid the physician in daily clinical practice and will ensure optimal care for patients with MM. Leukemia (2009) 23, 1716-1730; doi: 10.1038/leu.2009.122; published online 4 June 2009 C1 [Palumbo, A.; Bringhen, S.; Boccadoro, M.] Univ Turin, Div Ematol, Osped Molinette, Azienda Osped S Giovanni Battista, I-10126 Turin, Italy. [Sezer, O.] Charite Univ Med Berlin, Dept Hematol Oncol, Berlin, Germany. [Kyle, R.; Kumar, S.; Dispenzieri, A.] Mayo Clin, Div Hematol, Rochester, MN USA. [Miguel, J. S.; Mateos, M.] CSIC, Serv Hematol, Hosp Univ Salamanca, CIC,USAL,IBMCC, Salamanca, Spain. [Orlowski, R. Z.; Giralt, S.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Moreau, P.] Univ Hosp, Dept Clin Hematol, Nantes, France. [Niesvizky, R.] Cornell Univ, Weill Med Coll, Ctr Lymphoma & Myeloma, New York, NY 10021 USA. [Morgan, G.; Davies, F.] Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. [Comenzo, R.] Tufts Med Ctr, Blood Bank, Boston, MA USA. [Comenzo, R.] Tufts Med Ctr, Stem Cell Proc Lab, Boston, MA USA. [Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Hajek, R.] Univ Hosp Brno, Dept Internal Med, Brno, Czech Republic. [Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cavo, M.] Inst Hematol & Med Oncol, Bologna, Italy. [Blade, J.] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain. [Einsele, H.] Univ Klin Wurzburg, Med Klin & Poliklin 2, Wurzburg, Germany. [Dimopoulos, M. A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Spencer, A.] Alfred Hosp, Dept Haematol, Melbourne, Vic, Australia. [Reiman, T.] Cross Canc Inst, Dept Med, Edmonton, AB T6G 1Z2, Canada. [Shimizu, K.] Nagoya City Midori Gen Hosp, Dept Internal Med, Nagoya, Aichi, Japan. [Lee, J. H.] Gachon Univ, Gil Hosp, Div Hematol Oncol, Inchon, South Korea. [Attal, M.] Hop Purpan, Serv Hematol, Dept Hematol, Toulouse, France. [Attal, M.] Hop Purpan, Serv Hematol, Dept Biostat, Toulouse, France. [Chen, W.] Capital Med Univ, Beijing Chaoyang Hosp, Dept Hematol, Beijing, Peoples R China. [Chen, W.] Capital Med Univ, Beijing Chaoyang Hosp, Dept Oncol, Beijing, Peoples R China. [Ludwig, H.] Wilhelminenspital Stadt Wien, Dept Med 1, Vienna, Austria. [Joshua, D.] Bosch Univ Sydney, Royal Prince Alfred Hosp, Inst Hematol, Camperdown, NSW, Australia. [Chim, J.] Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Hungria, V.] Clin Sao Germano, Dept Hematol, Sao Paulo, Brazil. [Turesson, I.] Malmo Univ Hosp, Dept Med Hematol, Malmo, Sweden. [Durie, B. G. M.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Aptium Oncol Inc, Los Angeles, CA USA. [Lonial, S.] Emory Univ, Dept Hematol, Atlanta, GA 30322 USA. RP Palumbo, A (reprint author), Univ Turin, Div Ematol, Osped Molinette, Azienda Osped S Giovanni Battista, Via Genova 3, I-10126 Turin, Italy. EM appalumbo@yahoo.com RI 2009, Secribsal/A-1266-2012; Hungria, Vania/G-3141-2012; Waage, Anders/D-7705-2013; Sangue, Inct/I-1919-2013; FACON, THIERRY/M-9736-2014; Kumar, Shaji/A-9853-2008; richard, chrystelle/K-8595-2015; OI Dispenzieri, Angela/0000-0001-8780-9512; FACON, THIERRY/0000-0001-7705-8460; Kumar, Shaji/0000-0001-5392-9284; CAVO, MICHELE/0000-0003-4514-3227 NR 71 TC 83 Z9 84 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2009 VL 23 IS 10 BP 1716 EP 1730 DI 10.1038/leu.2009.122 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 506YX UT WOS:000270816300005 PM 19494840 ER PT J AU Giralt, S Stadtmauer, EA Harousseau, JL Palumbo, A Bensinger, W Comenzo, RL Kumar, S Munshi, NC Dispenzieri, A Kyle, R Merlini, G San Miguel, J Ludwig, H Hajek, R Jagannath, S Blade, J Lonial, S Dimopoulos, MA Einsele, H Barlogie, B Anderson, KC Gertz, M Attal, M Tosi, P Sonneveld, P Boccadoro, M Morgan, G Sezer, O Mateos, MV Cavo, M Joshua, D Turesson, I Chen, W Shimizu, K Powles, R Richardson, PG Niesvizky, R Rajkumar, SV Durie, BGM AF Giralt, S. Stadtmauer, E. A. Harousseau, J. L. Palumbo, A. Bensinger, W. Comenzo, R. L. Kumar, S. Munshi, N. C. Dispenzieri, A. Kyle, R. Merlini, G. San Miguel, J. Ludwig, H. Hajek, R. Jagannath, S. Blade, J. Lonial, S. Dimopoulos, M. A. Einsele, H. Barlogie, B. Anderson, K. C. Gertz, M. Attal, M. Tosi, P. Sonneveld, P. Boccadoro, M. Morgan, G. Sezer, O. Mateos, M. V. Cavo, M. Joshua, D. Turesson, I. Chen, W. Shimizu, K. Powles, R. Richardson, P. G. Niesvizky, R. Rajkumar, S. V. Durie, B. G. M. CA IMWG TI International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100) SO LEUKEMIA LA English DT Article DE myeloma; plerixafor; stem cell collection; high-dose therapy; IMWG; guidelines ID COLONY-STIMULATING FACTOR; IDENTICAL SIBLING TRANSPLANTATION; VERSUS-HOST-DISEASE; NEWLY-DIAGNOSED MYELOMA; BLOOD PROGENITOR CELLS; AUTOLOGOUS TRANSPLANTATION; G-CSF; ENGRAFTMENT KINETICS; ALLOGENEIC TRANSPLANTATION; CYCLOPHOSPHAMIDE PLUS AB Multiple myeloma is the most common indication for high-dose chemotherapy with autologous stem cell support (ASCT) in North America today. Stem cell procurement for ASCT has most commonly been performed with stem cell mobilization using colony-stimulating factors with or without prior chemotherapy. The target CD34+ cell dose to be collected as well as the number of apheresis performed varies throughout the country, but a minimum of 2 million CD34+ cells/kg has been traditionally used for the support of one cycle of high-dose therapy. With the advent of plerixafor (AMD3100) (a novel stem cell mobilization agent), it is pertinent to review the current status of stem cell mobilization for myeloma as well as the role of autologous stem cell transplantation in this disease. On June 1, 2008, a panel of experts was convened by the International Myeloma Foundation to address issues regarding stem cell mobilization and autologous transplantation in myeloma in the context of new therapies. The panel was asked to discuss a variety of issues regarding stem cell collection and transplantation in myeloma especially with the arrival of plerixafor. Herein, is a summary of their deliberations and conclusions. Leukemia (2009) 23, 1904-1912; doi: 10.1038/leu.2009.127; published online 25 June 2009 C1 [Giralt, S.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Stadtmauer, E. A.] Univ Penn, Bone Marrow & Stem Cell Transplant Program, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Harousseau, J. L.] Inst Biol, Dept Hematol, Nantes, France. [Palumbo, A.; Boccadoro, M.] Univ Turin, Osped Molinette, Azienda Osped S Giovanni Battista, Div Ematol, Turin, Italy. [Bensinger, W.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Comenzo, R. L.] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA. [Kumar, S.; Dispenzieri, A.; Kyle, R.; Gertz, M.; Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, MN USA. [Munshi, N. C.; Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [San Miguel, J.; Mateos, M. V.] CSIC, USAL, Dept Hematol, Serv Hepatol,Hosp Univ Salamanca,CIC,IBMCC, Madrid, Spain. [Ludwig, H.] Wilhelminenspital Stat Wien, Med Dept & Oncol 1, Vienna, Austria. [Hajek, R.] Dept Internal Med Fn Brno & LF MM Brno, Brno, Czech Republic. [Jagannath, S.] St Vincent Catholic Med Ctr, Dept Med, Multiple Myeloma & Bone Marrow Stem Cell Transpla, New York, NY USA. [Blade, J.] Hosp Clin Barcelona, IDIBAPS, Dept Hematol, Barcelona, Spain. [Lonial, S.] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Dimopoulos, M. A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Einsele, H.] Univ Wurzburg, Dept Internal Med, Wurzburg, Germany. [Barlogie, B.] MIRT UAMS, Dept Hematol, Little Rock, AR USA. [Barlogie, B.] MIRT UAMS, Dept Pathol, Little Rock, AR USA. [Attal, M.] Hop Purpan, Dept Hematol, Toulouse, France. [Attal, M.] Hop Purpan, Dept Biostat, Toulouse, France. [Tosi, P.] Univ Bologna, Inst Hematol & Med Oncol, Bologna, Italy. [Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Morgan, G.] Leukemia & Myeloma Program, Dept Hematol Oncol, Wimbledon, England. [Sezer, O.] Univ Berlin, Dept Hematol Oncol, Berlin, Germany. [Cavo, M.] Inst Hematol & Med Oncol Seragnoli, Bologna, Italy. [Joshua, D.] Univ Sydney, Bosch Inst, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. [Turesson, I.] Malmo Univ Hosp, Dept Hematol Oncol, Malmo, Sweden. [Chen, W.] Capital Med Univ, Beijing Chaoyang Hosp, Dept Hematol Oncol, Beijing, Peoples R China. [Shimizu, K.] Nagoya City Midori Gen Hosp, Dept Internal Med, Nagoya, Aichi, Japan. [Powles, R.] Parkside Canc Ctr, Dept Hematol Oncol, London, England. [Niesvizky, R.] Cornell Univ, Weill Med Coll, Ctr Lymphoma & Myeloma, New York, NY 10021 USA. [Durie, B. G. M.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Aptium Oncol Inc, Los Angeles, CA USA. RP Giralt, S (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Unit 423, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM sgiralt@mdanderson.org RI 2009, Secribsal/A-1266-2012; Waage, Anders/D-7705-2013; FACON, THIERRY/M-9736-2014; Kumar, Shaji/A-9853-2008; OI FACON, THIERRY/0000-0001-7705-8460; Kumar, Shaji/0000-0001-5392-9284; CAVO, MICHELE/0000-0003-4514-3227; Rajkumar, S. Vincent/0000-0002-5862-1833; Merlini, Giampaolo/0000-0001-7680-3254; SAN MIGUEL, JESUS/0000-0002-9183-4857; Dispenzieri, Angela/0000-0001-8780-9512 NR 53 TC 107 Z9 110 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2009 VL 23 IS 10 BP 1904 EP 1912 DI 10.1038/leu.2009.127 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 506YX UT WOS:000270816300024 PM 19554029 ER PT J AU Frank, NY Frank, MH AF Frank, Natasha Y. Frank, Markus H. TI ABCB5 gene amplification in human leukemia cells SO LEUKEMIA RESEARCH LA English DT Editorial Material ID BINDING CASSETTE TRANSPORTER; P-GLYCOPROTEIN; CHEMORESISTANCE; EXPRESSION; MELANOMA C1 [Frank, Markus H.] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, W Roxbury, MA 02132 USA. RP Frank, MH (reprint author), Childrens Hosp, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM mfrank@rics.bwh.harvard.edu RI Frank, Markus/O-1625-2014 OI Frank, Markus/0000-0002-1312-0488 FU NCI NIH HHS [R01 CA113796-04, R01 CA138231, R01 CA138231-01, R01 CA113796, R01 CA113796-01A1] NR 13 TC 7 Z9 11 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 2009 VL 33 IS 10 BP 1303 EP 1305 DI 10.1016/j.leukres.2009.04.035 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 475QO UT WOS:000268375500004 PM 19477512 ER PT J AU Heller, JC Prochazka, AV Everson, GT Forman, LM AF Heller, J. Christie Prochazka, Allan V. Everson, Gregory T. Forman, Lisa M. TI Long-Term Management After Liver Transplantation: Primary Care Physician Versus Hepatologist SO LIVER TRANSPLANTATION LA English DT Article ID METABOLIC SYNDROME; DIABETES-MELLITUS; PREVALENCE; OBESITY AB As long-term survival after liver transplantation increases, metabolic complications are becoming increasingly prevalent. Given concerns about which group of providers should be managing liver recipients and how well metabolic complications are managed, we administered a postal survey to 280 transplant hepatologists to determine attitudes, perceptions, and practice patterns in the management of metabolic complications after transplantation. The response rate was 68.2%. There was great variation in patterns of practice across the United States with respect to the number of posttransplant clinics, clinic format, and number of recipients cared for per week. Hepatologists, primary care physicians (PCPs), and surgeons were primarily responsible for the overall care of liver recipients 1 year or more after liver transplantation according to 66%, 24%, and 8% of respondents, respectively. Hepatologists felt that metabolic complications were common, but few strongly agreed that hypertension (33.3%), chronic renal insufficiency (3.8%), diabetes mellitus (8.8%), dyslipidemia (111.1%), and bone disease (12.8%) were well controlled. The majority of hepatologists indicated that ideally PCPs should be managing recipients' hypertension, diabetes mellitus, dyslipidemia, and bone disease (78.8%, 63.1%, 78.3%, and 72.5%), but they felt that in actuality, PCPs were managing these conditions less frequently (45.4%, 51.4%, 44.6%, and 38%). In conclusion, metabolic complications are perceived to be common but not well controlled post-transplant, and most hepatologists feel that PCPs should take a more active role in the management of these complications. Future studies are needed to identify barriers to care in the treatment of metabolic complications post-transplant with the goal of improving long-term morbidity and mortality. Liver Transpl 15:1330-1335, 2009. (C) 2009 AASLD. C1 [Heller, J. Christie; Everson, Gregory T.; Forman, Lisa M.] Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Denver, CO USA. [Prochazka, Allan V.] Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Denver, CO 80262 USA. [Prochazka, Allan V.] Denver VA Hosp, Div Ambulatory Care, Denver, CO USA. RP Forman, LM (reprint author), Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, 1635 Aurora Court,B-154, Aurora, CO 80045 USA. EM lisa.forman@ucdenver.edu FU American Society of Transplantation/Schering Plough Women; Minority Career Development Faculty FX This study was funded in part by an American Society of Transplantation/Schering Plough Women and Minority Career Development Faculty Grant. NR 14 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2009 VL 15 IS 10 BP 1330 EP 1335 DI 10.1002/lt.21786 PG 6 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 508LB UT WOS:000270931500026 PM 19790168 ER PT J AU Yu, L Koepsell, T Manhart, L Ioannou, G AF Yu, Lei Koepsell, Thomas Manhart, Lisa Ioannou, George TI Survival After Orthotopic Liver Transplantation: The Impact of Antibody Against Hepatitis B Core Antigen in the Donor SO LIVER TRANSPLANTATION LA English DT Article ID HBC POSITIVE DONORS; VIRUS INFECTION; GRAFT-SURVIVAL; ISCHEMIA TIME; ALLOGRAFTS; TRANSMISSION; RECIPIENTS; LAMIVUDINE; RISK; REACTIVATION AB Liver transplantation using grafts from donors with antibody against hepatitis B core antigen (anti-HBc) increases the recipients' risk of developing hepatitis B virus (HBV) infection post-transplantation. Our aim was to assess whether using such grafts was associated with reduced posttransplantation survival and whether this association depended on recipients' prior exposure to HBV on the basis of their pretransplantation serological patterns. Data were derived from the United Network for Organ Sharing on adult, cadaveric, first-time liver transplants performed between 1994 and 2006. Among recipients who did not have HBV infection before transplantation, those with anti-HBc-positive donors had significantly worse unadjusted posttransplantation patient survival than recipients with anti-HBc-negative donors [hazard ratio, 1.35; 95% confidence interval (CI), 1.21-1.50). However, after adjustments for other predictors of posttransplantation survival, including donor age, donor race, and recipient underlying liver diseases, patient survival was not significantly different between the 2 groups (hazard ratio, 1.09; 95% CI, 0.97-1.24). Among recipients without antibody against hepatitis B surface antigen (anti-HBs), use of anti-HBc-positive donor grafts was associated with a trend toward worse survival (adjusted hazard ratio, 1.18; 95% CI, 0.95-1.46), whereas no such trend was observed among recipients positive for anti-HBs. In conclusion, in patients without HBV infection before transplantation, using anti-HBc-positive donors was not independently associated with worse posttransplantation survival. Matching these donors to recipients with anti-HBs pre-transplantation may be especially safe. Liver Transpl 15:1343-1350, 2009. (C) 2009 AASLD. C1 [Yu, Lei] Univ Washington, Dept Med, Div Gastroenterol, Sch Med, Seattle, WA 98195 USA. [Yu, Lei; Ioannou, George] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. [Yu, Lei; Ioannou, George] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. [Yu, Lei; Koepsell, Thomas; Manhart, Lisa] Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. RP Yu, L (reprint author), Univ Washington, Dept Med, Div Gastroenterol, Sch Med, 1959 NE Pacific St,Box 356424, Seattle, WA 98195 USA. EM leiy@medicine.washington.edu FU American Liver Foundation; American Association for the Study of Liver Diseases through the Jan Albrecht Award; National Institutes of Health; Health Resources and Services Administration [231-00-0115] FX This research was supported by the American Liver Foundation and American Association for the Study of Liver Diseases through the Jan Albrecht Award (to G. Ioannou), by the Veterans Affairs Puget Sound Health Care System through the Research Enhancement Award Program (to L. Yu), by the National Institutes of Health through a T32 training grant (to L. Yu), and by the Health Resources and Services Administration (contract 231-00-0115). NR 30 TC 25 Z9 25 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2009 VL 15 IS 10 BP 1343 EP 1350 DI 10.1002/lt.21788 PG 8 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 508LB UT WOS:000270931500028 PM 19790164 ER PT J AU Namjou, B Scofield, RH Kelly, JA Goodmon, EL Aberle, T Bruner, GR Harley, JB AF Namjou, B. Scofield, R. H. Kelly, J. A. Goodmon, E. L. Aberle, T. Bruner, G. R. Harley, J. B. TI The effects of previous hysterectomy on lupus SO LUPUS LA English DT Article DE anti-DNA antibodies; nephritis; systemic lupus erythematosus ID UNITED-STATES; ERYTHEMATOSUS; SEX; PREVALENCE; WOMEN; AGE AB Hysterectomy is one of the most common surgical procedures performed in United States, and currently, one in three women in United States has had a hysterectomy by the age of 60 years. Systemic lupus erythematosus (SLE) is a common autoimmune disease and especially targets women of childbearing age at least 10 times higher than men, which reflects the major role of female sex hormones. In this retrospective study, we evaluate the potential effects of previous hysterectomy in our lupus cohort. Data collected from study subject questionnaires were obtained from the Lupus Family Registry and Repository (LFRR) at the Oklahoma Medical Research Foundation. Hysterectomy data were available from 3389 subjects. SLE patients with a positive history of hysterectomy have been selected and compared with matched lupus patients with a negative history of hysterectomy and healthy controls. Association analyses were performed, and the P values and adjusted odds ratios (ORs) were calculated. SLE patients with a negative history of hysterectomy more likely had kidney nephritis or positive anti-dsDNA than age-matched SLE patients with a history of hysterectomy before disease onset. This effect was independent of ethnicity with an OR of 6.66 (95% CI = 3.09-14.38, P = 1.00 x 10(-8)) in European patients and 2.74 (95% CI = 1.43-5.25, P = 0.001) in African-Americans. SLE patients with a positive history of hysterectomy before disease onset also had a later age of disease onset (P = 0.0001) after adjustment for age and race. Our findings support the notion that the influence of female sex hormones in SLE and various clinical findings are tremendous and that surgical menopause such as this could significantly affect the outcome of disease and clinical manifestations. Lupus (2009) 18, 1000-1005. C1 [Namjou, B.; Scofield, R. H.; Kelly, J. A.; Goodmon, E. L.; Aberle, T.; Bruner, G. R.; Harley, J. B.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Harley, J. B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Harley, J. B.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM john-harley@omrf.org FU NIH [AR42460, RR015577, AI31584, AR12253, AR48940, DE015223, RR020143, AI062629, AI24717, AI07633, AR62277]; U.S. Department of Veterans Affairs FX This work was supported by the NIH (AR42460, RR015577, AI31584, AR12253, AR48940, DE015223, RR020143, AI062629, AI24717, AI07633 and AR62277) and the U.S. Department of Veterans Affairs. NR 15 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PD OCT PY 2009 VL 18 IS 11 BP 1000 EP 1005 DI 10.1177/0961203309104315 PG 6 WC Rheumatology SC Rheumatology GA 495AW UT WOS:000269862600010 PM 19762402 ER PT J AU Varadarajan, KM Harry, RE Johnson, T Li, GA AF Varadarajan, Kartik M. Harry, Rubash E. Johnson, Todd Li, Guoan TI Can in vitro systems capture the characteristic differences between the flexion-extension kinematics of the healthy and TKA knee? SO MEDICAL ENGINEERING & PHYSICS LA English DT Review DE Knee kinematics; Oxford knee rig; Robotic testing system; Total knee arthroplasty ID ANTERIOR CRUCIATE LIGAMENT; VIVO FLUOROSCOPIC ANALYSIS; JOINT KINEMATICS; WEIGHT-BEARING; ARTHROPLASTY KINEMATICS; CONTACT KINEMATICS; ARTICULAR SURFACES; FEMORAL ROLLBACK; REACTION FORCES; MOTION ANALYSIS AB In vitro systems provide a powerful means to evaluate the efficacy of total knee arthroplasty (TKA) in restoring normal knee kinematics The Oxford knee rig (OKR) and the robotic knee testing system (RKTS) represent two systems that have been extensively used to study TKA biomechanics. Nonetheless, a frequently asked question is whether in vitro simulations can capture the in vivo behavior of the knee. Here, we compared the flex ion-extension kinematics of intact knees and knees after TKA tested on the OKR and RKTS, to results of representative in vivo studies. The goal was to determine if the in vitro systems could capture the key kinematic features of knees in healthy subjects and TKA patients Results showed that the RKTS and the OKR can replicate the femoral rollback and 'screw home' tibial rotation between 0 degrees and 30 degrees flexion seen in healthy subjects, and the reduced femoral rollback and absence of 'screw home' motion in TKA patients The RKTS also replicated the overall internally rotated position of the tibia beyond 30 degrees flexion However. ability of the OKR to replicate the internally rotated position of the knee beyond 30 degrees flexion was inconsistent. These data could aid in validation of new in vitro systems and physiologic interpretations of in vitro results. (C) 2009 IPEM. Published by Elsevier Ltd All rights reserved. C1 [Li, Guoan] Harvard Univ, Sch Med, MGH, Bioengn Lab, Boston, MA 02114 USA. [Varadarajan, Kartik M.; Harry, Rubash E.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Varadarajan, Kartik M.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Johnson, Todd] Zimmer Inc, Warsaw, IN USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, MGH, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. FU Zimmer Inc. FX This work was supported by a research grant from Zimmer Inc. and one of the co-authors is an employee of Zimmer Inc. No coauthors received any benefits for this work. NR 85 TC 28 Z9 28 U1 2 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0951-8320 J9 MED ENG PHYS JI Med. Eng. Phys. PD OCT PY 2009 VL 31 IS 8 BP 899 EP 906 DI 10.1016/j.medengphy.2009.06.005 PG 8 WC Engineering, Biomedical SC Engineering GA 512BV UT WOS:000271218400002 PM 19595621 ER PT J AU Park, SJ Ionascu, D Hacker, F Mamon, H Berbeco, R AF Park, Sang-June Ionascu, Dan Hacker, Fred Mamon, Harvey Berbeco, Ross TI Automatic marker detection and 3D position reconstruction using cine EPID images for SBRT verification SO MEDICAL PHYSICS LA English DT Article DE automatic marker detection; 3D position reconstruction; cine EPID; SBRT verification ID IMPLANTED FIDUCIAL MARKERS; SCALE SELECTION; EDGE-DETECTION; RADIOTHERAPY; TRACKING; KV; MV; FEASIBILITY; ALGORITHM; MODE AB In previous studies, an electronic portal imaging device (EPID) in cine mode was used for validating respiratory gating and stereotactic body radiation therapy (SBRT) by tracking implanted fiducials. The manual marker tracking methods that were used were time and labor intensive, limiting the utility of the validation. The authors have developed an automatic algorithm to quickly and accurately extract the markers in EPID images and reconstruct their 3D positions. Studies have been performed with gold fiducials placed in solid water and dynamic thorax phantoms. In addition, the authors have examined the cases of five patients being treated under an SBRT protocol for hepatic metastases. For each case, a sequence of images was created by collecting the exit radiation using the EPID. The markers were detected and recognized using an image processing algorithm based on the Laplacian of Gaussian function. To reduce false marker detection, a marker registration technique was applied using image intensity as well as the geometric spatial transformations between the reference marker positions produced from the projection of 3D CT images and the estimated marker positions. An average marker position in 3D was reconstructed by backprojecting, towards the source, the position of each marker on the 2D image plane. From the static phantom study, spatial accuracies of <1 mm were achieved in both 2D and 3D marker locations. From the dynamic phantom study, using only the Laplacian of the Gaussian algorithm, the marker detection success rate was 88.8%. However, adding a marker registration technique which utilizes prior CT information, the detection success rate was increased to 100%. From the SBRT patient study, intrafractional tumor motion (3.1-11.3 mm) in the SI direction was measured using the 2D images. The interfractional patient setup errors (0.1-12.7 mm) in the SI, AP, and LR directions were obtained from the average marker locations reconstructed in 3D and compared to the reference planning CT image. The authors have developed an automatic algorithm to extract marker locations from MV images and have evaluated its performance. The measured intrafractional tumor motion and the interfractional daily patient setup error can be used for off-line retrospective verification of SBRT. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3218845] C1 [Park, Sang-June; Ionascu, Dan; Hacker, Fred; Mamon, Harvey; Berbeco, Ross] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Park, SJ (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. EM spark@lroc.harvard.edu OI Hacker, Fred/0000-0001-7535-7598 FU Varian Medical Systems, Inc.; Joint Center for Radiation Therapy (JCRT) Foundation FX This work was partially supported by grants from Varian Medical Systems, Inc. and the Joint Center for Radiation Therapy (JCRT) Foundation. NR 17 TC 25 Z9 27 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2009 VL 36 IS 10 BP 4536 EP 4546 DI 10.1118/1.3218845 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 499SO UT WOS:000270246000024 PM 19928085 ER PT J AU Bennett, GG Wolin, KY Puleo, EM Masse, LC Atienza, AA AF Bennett, Gary G. Wolin, Kathleen Y. Puleo, Elaine M. Masse, Louise C. Atienza, Audie A. TI Awareness of National Physical Activity Recommendations for Health Promotion among US Adults SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE HINTS; EXERCISE; DIET; PHYSICAL INACTIVITY ID AMERICAN-HEART-ASSOCIATION; OF-SPORTS-MEDICINE; PERCEIVED RISK; CANCER-SOCIETY; PUBLIC-HEALTH; UNITED-STATES; DISEASE; PREVENTION; KNOWLEDGE; AGENDA AB BENNETT, G. G., K. Y. WOLIN. E. M. PULEO, L. C. MASSE, and A. A. ATIENZA. Awareness of National Physical Activity Recommendations for Health Promotion among US Adults. Med. Sci. Sports Exerc., Vol. 41, No. 10, pp. 1849-1855, 2009. Purpose: To examine whether knowledge of the 1995 Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) national physical activity recommendations varies by sociodemographic, behavioral, and communication-related factors. Methods: Cross-sectional analyses of 2381 participants in the 2005 Health Information National Trends Survey, a national probability sample of the US population contacted via random-digit dial. Results: Only a third of respondents were accurately knowledgeable of the CDC/ACSM physical activity recommendations. Recommendation knowledge was higher among women (OR 1.70; 95% confidence interval (CI) = 1.35-2.14) than men, the employed compared with those not currently working (OR = 0.73 95% CI = 0.55-0.95), foreign-born individuals (OR = 1.62; 95% CI = 1.15-2.30) compared with the US-born, and those meeting CDC/ACSM recommendations vs those who do not (OR = 0.74: 95% CI = 0.58-0.96). Conclusions: There is riot widespread knowledge of the consensus national physical activity recommendations. These findings highlight the need for more effective campaigns to promote physical activity among the American public. C1 [Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bennett, Gary G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolin, Kathleen Y.] Washington Univ, Sch Med, St Louis, MO USA. [Puleo, Elaine M.] Univ Massachusetts Amherst, Amherst, MA USA. [Masse, Louise C.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Atienza, Audie A.] NCI, Bethesda, MD 20892 USA. RP Bennett, GG (reprint author), Duke Univ, Box 90086,9 Flowers Dr, Durham, NC 27708 USA. EM gary.bennett@duke.edu RI Wolin, Kathleen/I-2154-2014 OI Wolin, Kathleen/0000-0001-7950-9042 FU Dana-Farber/ Harvard Cancer Center; NCI [1K22CA126992]; US NCI FX Present address for Gary G. Bennett is Duke University, Durham, NC. NR 46 TC 30 Z9 30 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD OCT PY 2009 VL 41 IS 10 BP 1849 EP 1855 DI 10.1249/MSS.0b013e3181a52100 PG 7 WC Sport Sciences SC Sport Sciences GA 499FI UT WOS:000270202700003 PM 19727030 ER PT J AU Thameem, F Puppala, S He, X Arar, NH Stern, MP Blangero, J Duggirala, R Abboud, HE AF Thameem, Farook Puppala, Sobha He, Xin Arar, Nedal H. Stern, Michael P. Blangero, John Duggirala, Ravindranath Abboud, Hanna E. TI Evaluation of gremlin 1 (GREM1) as a candidate susceptibility gene for albuminuria-related traits in Mexican Americans with type 2 diabetes mellitus SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID GLOMERULAR-FILTRATION-RATE; MEASURED GENOTYPE; NEPHROPATHY; LINKAGE; EXPRESSION; DISEASE; GLUCOSE; SEARCH; KIDNEY; LIMB AB Several novel genes that are up-regulated in the kidney in diabetes have been identified including GREM1, which encodes gremlin 1. GREM1 maps to human chromosome 15q12, a region previously found to be linked to albumin to creatinine ratio (ACR) in Mexican Americans. The objective of this study is to investigate whether genetic variants in GREM1, a positional candidate gene, contribute to variation in ACR. By sequencing 32 individuals for both exons and 2-kilobase putative promoter region of GREM1, we identified 19 genetic variants including 5 in the promoter region and 13 in the 3' Untranslated region. Of 19 polymorphisms identified, 13 polymorphisms were genotyped in the entire cohort (N = 670, 39 large families) either by restriction fragment length polymorphism or by TaqMan (Applied Biosystems, Foster City, CA) assays. Association analyses between the genotypes and ACR, type 2 diabetes mellitus, and related phenotypes were carried out using a measured genotype approach as implemented in the variance component analytical tools (SOLAR). of the variants examined for association, none exhibited statistically significant association with ACR after accounting for the effects of covariates such as age, sex, diabetes, duration of diabetes, systolic blood pressure, and antihypertensive medications. However, 2 novel variants at the 31 untranslated region showed significant association with estimated glomerular filtration rate (P = .010 and P = .049) and body mass index (P = .013 and P = .019) after accounting for trait-specific covariate influences. Furthermore, a novel variant located in the promoter exhibited a significant association with systolic (P = .038) and diastolic blood pressure (P = .005) after adjusting for the effects of age, sex, diabetes, and antihypertensive medications. In conclusion, the variants examined at GREM1 are not significant contributors to variation in ACR in Mexican Americans, although they appear to minimally influence risk factors related to ACR. (c) 2009 Elsevier Inc. All rights reserved. C1 [Thameem, Farook] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Thameem, Farook; Arar, Nedal H.; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, George OBrien Kidney Res Ctr, San Antonio, TX 78229 USA. [Puppala, Sobha; Blangero, John; Duggirala, Ravindranath] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78227 USA. [Arar, Nedal H.; Abboud, Hanna E.] S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Stern, Michael P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. RP Thameem, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. EM thameem@uthscsa.edu FU American Heart Association; Diabetes Action Research and Education Foundation; Satellite HealthCare; George O'Brien Kidney Research Center [P50 DK061597]; VA-Merit Review; National Institute of Diabetes, Digestive, and Kidney Diseases [DK42273, DK47482, DK53889]; National Center for Research Resources [UL1 RR025767, KL2 RR025766] FX We thank members of the SAFDGS for their participation and cooperation. This Study was Supported by a Scientist Development Grant from the American Heart Association (FT), Diabetes Action Research and Education Foundation (FT), Satellite HealthCare (FT), George O'Brien Kidney Research Center (P50 DK061597; HEA, FT), VA-Merit Review (HEA, NHA), and grants from the National Institute of Diabetes, Digestive, and Kidney Diseases (NIPS: DK42273, DK47482; RD: DK53889). This work was also Supported by the National Center for Research Resources contracts UL1 RR025767 and KL2 RR025766 for the Institute for Integration of Medicine and Science. We also thank the General Clinical Research Center, South Texas Healthcare System. NR 22 TC 5 Z9 5 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2009 VL 58 IS 10 BP 1496 EP 1502 DI 10.1016/j.metabol.2009.04.039 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 500TF UT WOS:000270327100020 PM 19577778 ER PT J AU Brown, M AF Brown, Mark TI Military Chemical Warfare Agent Human Subjects Testing: Part 1-History of Six-Decades of Military Experiments With Chemical Warfare Agents SO MILITARY MEDICINE LA English DT Article AB Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns of possible long-term health consequences. Clinical and research evaluation of potential long-term health effects has been difficult because the exposures occurred decades ago, the identity of troops exposed and exposure magnitudes are uncertain, and acute effects during experiments poorly documented. In contrast, a companion article describes the large amount of information available about the specific agents tested and their long-term health effects. This short history describes U.S. military chemical-agent experiments with human subjects and identifies tested agents. Finally, the demonstrated need to anticipate future health concerns from military personnel involved in such military testing suggests current and future military researchers should be required, by law and regulation, to fully record the identity of those exposed, relevant exposure magnitude, and complete medical information for all subjects. New study protocols and institutional review board approvals for research involving military personnel should reflect this need. C1 US Dept Vet Affairs, Environm Agents Serv, Washington, DC 20420 USA. RP Brown, M (reprint author), US Dept Vet Affairs, Environm Agents Serv, 810 Vermont Ave NW, Washington, DC 20420 USA. NR 10 TC 4 Z9 4 U1 0 U2 1 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2009 VL 174 IS 10 BP 1041 EP 1048 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 601LI UT WOS:000278060500006 PM 19891215 ER PT J AU Brown, M AF Brown, Mark TI Military Chemical Warfare Agent Human Subjects Testing: Part 2-Long-Term Health Effects Among Participants of US Military Chemical Warfare Agent Testing SO MILITARY MEDICINE LA English DT Article ID CHLOROBENZYLIDENE MALONONITRILE CS; POSTTRAUMATIC-STRESS-DISORDER; MUSTARD GAS; TOKYO SUBWAY; TEAR GAS; VETERANS; SARIN; EXPOSURE AB Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns about how their participation affected their health. A companion article describes the history of these experiments, and how the lack of clinical data hampers evaluation of long-term health consequences. Conversely, much information is available about specific agents tested and their long-term health effects in other populations, which may be invaluable for helping clinicians respond effectively to the health care and other needs of affected veterans. The following review describes tested agents and their known long-term health consequences. Although hundreds of chemicals were tested, they fall into only about a half-dozen pharmaceutical classes, including common pharmaceuticals; anticholinesterase agents including military nerve agents and pesticides; anticholinergic glycolic acid esters such as atropine; acetylcholine reactivators such as 2-PAM; psychoactive compounds including cannabinoids, phencyclidine, and LSD; and irritants including tear gas and riot control agents. C1 US Dept Vet Affairs, Environm Agents Serv, Washington, DC 20420 USA. RP Brown, M (reprint author), US Dept Vet Affairs, Environm Agents Serv, 810 Vermont Ave, Washington, DC 20420 USA. NR 25 TC 2 Z9 2 U1 0 U2 10 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2009 VL 174 IS 10 BP 1049 EP 1054 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 601LI UT WOS:000278060500007 PM 19891216 ER PT J AU Perez-Johnston, R Lin, D Carlos, CFD Sahani, D AF Perez-Johnston, R. Lin J, D. Carlos, C. Fernandez-Del Castillo Sahani, D. TI Management of intraductal papillary mucinous neoplasms of the pancreas SO MINERVA CHIRURGICA LA English DT Article DE Pancreas neoplasms, diagnosis; Pancreas neoplasms, therapy; Tomography, X-ray computed; Cholangiopancreatography, magnetic resonance ID FINE-NEEDLE-ASPIRATION; INTERNATIONAL CONSENSUS GUIDELINES; MULTIDETECTOR ROW CT; MR CHOLANGIOPANCREATOGRAPHY; CYSTIC LESIONS; CLINICOPATHOLOGICAL FEATURES; DIFFERENTIAL-DIAGNOSIS; SURGICAL RESECTION; PREDICTIVE FACTORS; FLUID ANALYSIS AB Over the last decade, the diagnosis and treatment of intraductal papillary mucinous tumors (IPMN) of the pancreas has evolved. They represent a spectrum of disease, ranging from benign to malignant lesions, making the early detection and characterization of these lesions important. Several non-invasive and invasive imaging modalities allow adequate visualization of these lesions. Multidetec-tor computed tomography (MCT) and magnetic resonance (MR) Cholangiopancreatography are generally used as fist line imaging techniques, whereas invasive techniques as endoscopic ultrasound or endoscopic retrograde cholangiopancreatography are usually considered in the setting of an uncertain diagnosis. Multiple factors have to be taken into consideration in order to establish an adequate management of these lesions. Main duct and combined IPMN, as well as branch duct lesions larger than 3 cm or containing aggressive features as solid component are considered indications for surgical resection. On the other hand, follow-up through imaging is advocated for small, benign appearing lesions, as well as for post-surgical patients. in the later setting, the follow-up protocol should consider the aggressiveness of the resected lesion and the surgical margins, in order to establish an optimal time interval of imaging. C1 [Perez-Johnston, R.; Sahani, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging,Dept Radiol, Boston, MA 02114 USA. [Lin J, D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Carlos, C. Fernandez-Del Castillo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sahani, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 54 TC 5 Z9 5 U1 0 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4733 J9 MINERVA CHIR JI Minerva Chir. PD OCT PY 2009 VL 64 IS 5 BP 477 EP 487 PG 11 WC Surgery SC Surgery GA 514CA UT WOS:000271370000004 PM 19859038 ER PT J AU Deshpande, V Sainani, NI Chung, RT Pratt, DS Mentha, G Rubbia-Brandt, L Lauwers, GY AF Deshpande, Vikram Sainani, Nisha I. Chung, Raymond T. Pratt, Daniel S. Mentha, Gilles Rubbia-Brandt, Laura Lauwers, Gregory Y. TI IgG4-associated cholangitis: a comparative histological and immunophenotypic study with primary sclerosing cholangitis on liver biopsy material SO MODERN PATHOLOGY LA English DT Article DE autoimmune pancreatitis; primary sclerosing cholangitis; IgG4; IgG4 associated cholangitis ID IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; AUTOIMMUNE PANCREATITIS; DISEASE; INVOLVEMENT AB IgG4-associated cholangitis is a steroid-responsive hepatobiliary inflammatory condition associated with autoimmune pancreatitis that clinically and radiologically mimics primary sclerosing cholangitis. In this study, we conducted a morphological and immunohistochemical analysis of liver material obtained from individuals with IgG4-associated cholangitis, and compared these with well-characterized cases of primary sclerosing cholangitis. The study group consisted of 10 patients ( 9 biopsy and 1 hepatectomy case) with IgG4-associated cholangitis and 17 patients with primary sclerosing cholangitis ( 16 needle biopsy and 1 hepatectomy case). All patients with IgG4-associated cholangitis had pancreatic involvement as well, and six pancreatectomy samples revealed characteristic histopathological features of autoimmune pancreatitis. Primary sclerosing cholangitis cases were defined by the presence of a characteristic ERCP appearance. Clinical, pathological, radiological, and follow-up data were recorded for all cases. Portal and periportal inflammation was graded according to Ishak's guidelines. Immunohistochemical stains for IgG and IgG4 were performed. The cohort of patients with IgG4-associated cholangitis ( mean age: 63 years) was older than individuals with primary sclerosing cholangitis ( mean age: 44 years). Seven of these cases showed intrahepatic biliary strictures. IgG4-associated cholangitis liver samples showed higher portal (P = 0.06) and lobular (P = 0.009) inflammatory scores. Microscopic portal-based fibro-inflammatory nodules that were composed of fibroblasts, plasma cells, lymphocytes, and eosinophils were exclusively observed in five of the IgG4-associated cholangitis cases (50%). More than 10 IgG4-positive plasma cells per HPF ( high power field) were observed in 6 of the IgG4-associated cholangitis cases ( mean: 60, range: 0-140 per HPF), whereas all primary sclerosing cholangitis cases showed significantly lesser numbers ( mean: 0.08, range: 0-1 per HPF). On a liver biopsy, the histological features of IgG4-associated cholangitis may be distinctive, and in conjunction with IgG4 immunohistochemical stain, may help distinguish this disease from primary sclerosing cholangitis. Modern Pathology ( 2009) 22, 1287-1295; doi: 10.1038/modpathol.2009.94; published online 24 July 2009 C1 [Deshpande, Vikram; Lauwers, Gregory Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. [Sainani, Nisha I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Rubbia-Brandt, Laura] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. [Chung, Raymond T.; Pratt, Daniel S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA USA. [Mentha, Gilles] Univ Hosp Geneva, Div Visceral & Transplantat Surg, Geneva, Switzerland. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM VDESHPANDE@PARTNERS.ORG NR 20 TC 63 Z9 67 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2009 VL 22 IS 10 BP 1287 EP 1295 DI 10.1038/modpathol.2009.94 PG 9 WC Pathology SC Pathology GA 501BV UT WOS:000270354900003 PM 19633647 ER PT J AU Rabinovsky, R Pochanard, P McNear, C Brachmann, SM Duke-Cohan, JS Garraway, LA Sellers, WR AF Rabinovsky, Rosalia Pochanard, Panisa McNear, Chontelle Brachmann, Saskia M. Duke-Cohan, Jonathan S. Garraway, Levi A. Sellers, William R. TI p85 Associates with Unphosphorylated PTEN and the PTEN-Associated Complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PTEN; PHOSPHOINOSITIDE 3-KINASE; PTEN/MMAC1 GENE; BREAST-CANCER; WHEAT-GERM; TRASTUZUMAB RESISTANCE; EXPRESSION ANALYSES; REGULATORY SUBUNIT; SOMATIC MUTATIONS; PROTEIN STABILITY AB The lipid phosphatase PTEN functions as a tumor suppressor by dephosphorylating the D3 position of phosphoinositide-3,4,5-trisphosphate, thereby negatively regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In mammalian cells, PTEN exists either as a monomer or as a part of a >600-kDa complex (the PTEN-associated complex [PAC]). Previous studies suggest that the antagonism of PI3K/AKT signaling by PTEN may be mediated by a nonphosphorylated form of the protein resident within the multiprotein complex. Here we show that PTEN associates with p85, the regulatory subunit of PI3K. Using newly generated antibodies, we demonstrate that this PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PAC and also includes the p110 beta isoform of PI3K. The PTEN-p85 association is enhanced by trastuzumab treatment and linked to a decline in AKT phosphorylation in some ERBB2-amplified breast cancer cell lines. Together, these results suggest that integration of p85 into the PAC may provide a novel means of downregulating the PI3K/AKT pathway. C1 [Rabinovsky, Rosalia; Pochanard, Panisa; McNear, Chontelle; Brachmann, Saskia M.; Duke-Cohan, Jonathan S.; Garraway, Levi A.; Sellers, William R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rabinovsky, Rosalia; Pochanard, Panisa; McNear, Chontelle; Brachmann, Saskia M.; Duke-Cohan, Jonathan S.; Garraway, Levi A.; Sellers, William R.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Rabinovsky, Rosalia; Pochanard, Panisa; McNear, Chontelle; Brachmann, Saskia M.; Duke-Cohan, Jonathan S.; Garraway, Levi A.; Sellers, William R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Garraway, Levi A.] Broad Inst, Cambridge, MA 02142 USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu; william.sellers@novartis.com OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU DOD [W81XWH-05-1-0029, R01CA085912-09]; Novartis Institute for Biomedical Research FX This work was supported by DOD W81XWH-05-1-0029 (R.R.) and R01CA085912-09 (W.R.S. and L.A.G.) and the Novartis Institute for Biomedical Research (W.R.S. and L.A.G.). NR 73 TC 47 Z9 50 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2009 VL 29 IS 19 BP 5377 EP 5388 DI 10.1128/MCB.01649-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 493AT UT WOS:000269706000016 PM 19635806 ER PT J AU Lin, CL Whang, EE Donner, DB Jiang, XF Price, BD Carothers, AM Delaine, T Leffler, H Nilsson, UJ Nose, V Moore, FD Ruan, DT AF Lin, Chi-lou Whang, Edward E. Donner, David B. Jiang, Xiaofeng Price, Brendan D. Carothers, Adelaide M. Delaine, Tamara Leffler, Hakon Nilsson, Ulf J. Nose, Vania Moore, Francis D., Jr. Ruan, Daniel T. TI Galectin-3 Targeted Therapy with a Small Molecule Inhibitor Activates Apoptosis and Enhances Both Chemosensitivity and Radiosensitivity in Papillary Thyroid Cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER; BREAST-CANCER; MOUSE MODEL; CELL-LINES; CARCINOMA; GROWTH; RADIOTHERAPY; DOXORUBICIN; LUNG AB Although most patients with papillary thyroid cancer (PTC) have favorable outcomes, some have advanced PTC that is refractory to external beam radiation and systemic chemotherapy. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with antiapoptotic activity that is consistently overexpressed in PTC. The purpose of this study is to determine if Gal-3 inhibition promotes apoptosis, chemosensitivity, and radiosensitivity in PTC. PTC cell lines (8505-C and TPC-1) and human ex vivo PTC were treated with a highly specific small molecule inhibitor of Gal-3 (Td131_1). Apoptotic activity was determined by flow cytometric analysis as well as caspase-3 and PARP cleavage. The minimum inhibitory concentrations of Td131_1 and doxorubicin were determined, and their combined effects were measured to test for synergistic activity. The effects of Td131_1 on radiosensitivity were determined by a clonogenic assay. Td131_1 promoted apoptosis, improved radiosensitivity, and synergistically enhanced chemosensitivity to doxorubicin in PTC cell lines. In PTC ex vivo, Td131_1 treatment alone induced the cleavage of caspase-3 and PARP. Td131_1 and doxorubicin together activated apoptosis in PTC ex vivo to a greater degree than their combined individual effects. Td131_1 activated apoptosis and had synergistic activity with doxorubicin in PTC. We conclude that Gal-3 targeted therapy is a promising therapeutic strategy for advanced PTC that is refractory to surgery and radioactive iodine therapy. (Mol Cancer Res 2009;7(10):1655-62) C1 [Lin, Chi-lou; Whang, Edward E.; Carothers, Adelaide M.; Moore, Francis D., Jr.; Ruan, Daniel T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Nose, Vania] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Donner, David B.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Jiang, Xiaofeng; Price, Brendan D.] Harvard Univ, Sch Med, Div Genom Stabil, Boston, MA 02115 USA. [Jiang, Xiaofeng; Price, Brendan D.] Harvard Univ, Sch Med, DNA Repair, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Leffler, Hakon] Lund Univ, Dept Lab Med, Sect MIG, Lund, Sweden. RP Ruan, DT (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. RI Nilsson, Ulf/L-3219-2014; OI Nilsson, Ulf/0000-0001-5815-9522; Leffler, Hakon/0000-0003-4482-8945 FU Swedish Research Council; Oile Engkvist Byggmastare Foundation FX Giant support: The Swedish Research Council and the Oile Engkvist Byggmastare Foundation (U Nilsson and H Leffler) NR 19 TC 39 Z9 40 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2009 VL 7 IS 10 BP 1655 EP 1662 DI 10.1158/1541-7786.MCR-09-0274 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 510CE UT WOS:000271064800007 PM 19825987 ER PT J AU Keshishian, H Addona, T Burgess, M Mani, DR Shi, X Kuhn, E Sabatine, MS Gerszten, RE Carr, SA AF Keshishian, Hasmik Addona, Terri Burgess, Michael Mani, D. R. Shi, Xu Kuhn, Eric Sabatine, Marc S. Gerszten, Robert E. Carr, Steven A. TI Quantification of Cardiovascular Biomarkers in Patient Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; C-REACTIVE PROTEIN; NATRIURETIC PEPTIDE; CLINICAL-CHEMISTRY; MULTIPLEXED ASSAYS; SEPTAL ABLATION; TROPONIN-I; SERUM; VALIDATION; ENRICHMENT AB Verification of candidate biomarkers requires specific assays to selectively detect and quantify target proteins in accessible biofluids. The primary objective of verification is to screen potential biomarkers to ensure that only the highest quality candidates from the discovery phase are taken forward into preclinical validation. Because antibody reagents for a clinical grade immunoassay often exist for a small number of candidates, alternative methodologies are required to credential new and unproven candidates in a statistically viable number of serum or plasma samples. Using multiple reaction monitoring coupled with stable isotope dilution MS, we developed quantitative, multiplexed assays in plasma for six proteins of clinical relevance to cardiac injury. The process described does not require antibodies for immunoaffinity enrichment of either proteins or peptides. Limits of detection and quantitation for each signature peptide used as surrogates for the target proteins were determined by the method of standard addition using synthetic peptides and plasma from a healthy donor. Limits of quantitation ranged from 2 to 15 ng/ml for most of the target proteins. Quantitative measurements were obtained for one to two signature peptides derived from each target protein, including low abundance protein markers of cardiac injury in the nanogram/milliliter range such as the cardiac troponins. Intra- and interassay coefficients of variation were predominantly <10 and 25%, respectively. The configured multiplex assay was then used to measure levels of these proteins across three time points in six patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy. These results are the first demonstration of a multiplexed, MS-based assay for detection and quantification of changes in concentration of proteins associated with cardiac injury in the low nanogram/ milliliter range. Our results also demonstrate that these assays retain the necessary precision, reproducibility, and sensitivity to be applied to novel and uncharacterized candidate biomarkers for verification of proteins in blood. Molecular & Cellular Proteomics 8: 2339-2349, 2009. C1 [Keshishian, Hasmik; Addona, Terri; Burgess, Michael; Mani, D. R.; Kuhn, Eric; Carr, Steven A.] MIT, Broad Inst, Cambridge, MA 02142 USA. [Keshishian, Hasmik; Addona, Terri; Burgess, Michael; Mani, D. R.; Kuhn, Eric; Carr, Steven A.] Harvard Univ, Cambridge, MA 02142 USA. [Shi, Xu; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Shi, Xu; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Carr, SA (reprint author), MIT, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM scarr@broad.mit.edu FU National Institutes of Health [1U24 CA126476-02]; NCI; NHLBI [U01-HL081341] FX This work was supported, in whole or in part, by National Institutes of Health Grants 1U24 CA126476-02 from the NCI as part of the NCI's Clinical Proteomic Technologies Initiative and U01-HL081341 from the NHLBI (to S. A. C., R. E. G., and M. S. S.). NR 26 TC 182 Z9 184 U1 2 U2 28 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2009 VL 8 IS 10 BP 2339 EP 2349 DI 10.1074/mcp.M900140-MCP200 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 502XC UT WOS:000270492700011 PM 19596694 ER PT J AU Mahon, MJ AF Mahon, Matthew J. TI The Parathyroid Hormone 1 Receptor Directly Binds to the FERM Domain of Ezrin, an Interaction that Supports Apical Receptor Localization and Signaling in LLC-PK1 Cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID OPOSSUM KIDNEY-CELLS; EXCHANGER REGULATORY FACTOR; PROTEIN-COUPLED-RECEPTORS; CAMP-MEDIATED INHIBITION; CARBOXYL-TERMINAL REGION; PHOSPHATE-TRANSPORT; PHOSPHOLIPASE-C; NA+/H+ EXCHANGER; ERM PROTEINS; BRUSH-BORDER AB PTH 1 receptor (PTH1R) regulates mineral ion homeostasis. Both apical and basolateral PTH1R subpopulations exist within the renal proximal tubule. The purpose of this research was to examine determinants within the PTH1R that direct apical localization. When expressed in LLC-PK1 cells, a proximal tubule cell model, the PTH1R localizes to both apical and basolateral membranes. The C terminus of the PTH1R contains a psd-95, discs large, ZO-1 domain interaction motif that binds the sodium-hydrogen exchanger regulatory factor 1 (NHERF-1), a renal tubule scaffold protein. Receptors lacking the psd-95, discs large, ZO-1 domain interaction motif (PTH1R-C Delta 4) partly localize to apical membranes, suggesting that additional factors may be involved. Ezrin, a membrane-cytoskeleton linking protein, directly binds NHERF-1 and thus links assembled complexes to actin. In vitro, subdomain C of the ezrin band 4.1, ezrin, radixin, domain interacts with the C-terminal tail of the PTH1R on a site that is mutually exclusive from the NHERF-1 interaction domain, suggesting the presence of a ternary complex. Mutating the lysine-arginine-lysine motif within the juxtamembrane region of the PTH1R C-terminal tail to alanines markedly disrupts interactions with the band 4.1, ezrin, radixin, domain of ezrin both in vitro and within cells. Inclusion of these mutations in the context of the full-length PTH1R disrupts apical localization with no effect on basolateral expression. Expression of a dominant-negative ezrin selectively disrupts apical expression and signaling of the PTH1R. However, dominant-negative ezrin does not affect expression or signaling of the basolateral PTH1R subpopulation. These findings reveal that direct ezrin interactions promote PTH1R apical localization and signaling in LLC-PK1 cells. (Molecular Endocrinology 23: 1691-1701, 2009) C1 [Mahon, Matthew J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Mahon, Matthew J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Mahon, MJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Their 10, Boston, MA 02114 USA. EM mahon@helix.mgh.harvard.edu FU National Institutes of Health [P01 DK073911] FX This work was supported by a grant from the National Institutes of Health (P01 DK073911). NR 57 TC 12 Z9 12 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2009 VL 23 IS 10 BP 1691 EP 1701 DI 10.1210/me.2009-0164 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 500AV UT WOS:000270270300016 PM 19608645 ER PT J AU Lau, KS Haigis, KM AF Lau, Ken S. Haigis, Kevin M. TI Non-redundancy within the RAS oncogene family: Insights into mutational disparities in cancer SO MOLECULES AND CELLS LA English DT Review DE cancer; mutation; RAS; signaling ID BLADDER-CARCINOMA ONCOGENE; K-RAS; N-RAS; TRANSFORMING GENES; PHOSPHOINOSITIDE 3-KINASE; HUMAN-MELANOMA; HA-RAS; COLORECTAL-CANCER; SARCOMA-VIRUSES; SCID MICE AB The RAS family of oncoproteins has been studied extensively for almost three decades. While we know that activation of RAS represents a key feature of malignant transformation for many cancers, we are only now beginning to understand the complex underpinnings of RAS biology. Here, we will discuss emerging cancer genome sequencing data in the context of what is currently known about RAS function. Taken together, retrospective studies of primary human tissues and prospective studies of experimental models support the notion that the variable mutation frequencies exhibited by the RAS oncogenes reflect unique functions of the RAS oncoproteins. C1 [Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Haigis, KM (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. EM khaigis@partners.org OI Lau, Ken/0000-0001-8438-0319 FU National Cancer Institute [K01-CA118425, P50-CA127003]; National Institute for General Medical Science [R01-GM088827]; American Cancer Society [MGO-114877]; Merlino Family Endowment Fund; Damon Runyon Cancer Research Foundation FX This review is meant to be a broad overview of RAS function as it relates to emerging cancer genome sequencing data. The authors would like to apologize to those investigators whose work we could not discuss in the limited space available. This work was supported by grants from the National Cancer Institute (K01-CA118425, P50-CA127003), the National Institute for General Medical Science (R01-GM088827), and the American Cancer Society (MGO-114877) and a donation from the Merlino Family Endowment Fund. K. L. is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation. NR 59 TC 27 Z9 27 U1 0 U2 3 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD OCT PY 2009 VL 28 IS 4 BP 315 EP 320 DI 10.1007/s10059-009-0143-7 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 522HA UT WOS:000271987300001 PM 19812895 ER PT J AU Qureshi, M Bedlack, R Cudkowicz, ME AF Qureshi, Muddasir Bedlack, Richards. Cudkowicz, Merit E. TI LYME DISEASE SEROLOGY IN AMYOTROPHIC LATERAL SCLEROSIS SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; Lyme disease; motor neuron disease; neuromuscular disease; neuroborreliosis; borrelia burgdorferi; serology ID BORRELIA-BURGDORFERI; ANTIBODIES AB Lyme disease is sometimes part of the differential diagnosis for amyotrophic lateral sclerosis (ALS). Herein we report on 414 individuals with ALS at the Massachusetts General Hospital who underwent laboratory testing for Lyme disease. Twenty-four (5.8%) were seropositive, but only 4 (0.97%) had confirmed past immunoreactive infection. Two of these patients received ceftriaxone for 1 month without clinical improvement. Lyme disease was rare in 414 patients with ALS and is not likely to be causative. Muscle Nerve 40: 626-628, 2009 C1 [Qureshi, Muddasir; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Charlestown, MA 02129 USA. [Qureshi, Muddasir; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Bedlack, Richards.] Duke Univ, Div Neurol, Durham, NC USA. [Bedlack, Richards.] Durham VA Med Ctr, Durham, NC USA. RP Qureshi, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, 13th St,Bldg 149,Room 2274, Charlestown, MA 02129 USA. EM mqureshi@partners.org NR 14 TC 10 Z9 10 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2009 VL 40 IS 4 BP 626 EP 628 DI 10.1002/mus.21438 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 506SA UT WOS:000270794900015 PM 19697382 ER PT J AU McCarthy, JR AF McCarthy, Jason R. TI The future of theranostic nanoagents SO NANOMEDICINE LA English DT Editorial Material ID DELIVERY; CANCER; NANOPARTICLES; THERAPY; TUMORS C1 [McCarthy, Jason R.] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [McCarthy, Jason R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McCarthy, JR (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM jason_mccarthy@hms.harvard.edu NR 11 TC 40 Z9 41 U1 2 U2 10 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD OCT PY 2009 VL 4 IS 7 BP 693 EP 695 DI 10.2217/NNM.09.58 PG 3 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 516MZ UT WOS:000271547900001 PM 19839803 ER PT J AU Peterson, RT AF Peterson, Randall T. TI DRUG DISCOVERY Propping up a destructive regime SO NATURE LA English DT Editorial Material ID CANCER C1 [Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Peterson, Randall T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Peterson, Randall T.] Broad Inst, Cambridge, MA USA. RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu NR 8 TC 9 Z9 9 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 1 PY 2009 VL 461 IS 7264 BP 599 EP 600 DI 10.1038/461599a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 500LH UT WOS:000270302600024 PM 19794479 ER PT J AU Locasale, JW Cantley, LC Heiden, MGV AF Locasale, Jason W. Cantley, Lewis C. Heiden, Matthew G. Vander TI Cancer's insatiable appetite SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID GLUCOSE-METABOLISM; TUMOR; PARAGANGLIOMA; MUTATIONS; SURVIVAL; PATHWAYS; GROWTH; CELLS; GENE AB Seemingly unrelated mutations that drive cancer share the ability to promote nutrient uptake and metabolism conducive to cell growth. C1 [Locasale, Jason W.; Cantley, Lewis C.; Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Locasale, Jason W.; Cantley, Lewis C.; Heiden, Matthew G. Vander] Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA. [Heiden, Matthew G. Vander] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Locasale, JW (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM Lewis_Cantley@hms.harvard.edu; Matthew_VanderHeiden@dfci.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Locasale, Jason/0000-0002-7766-3502 FU NCI NIH HHS [T32 CA009172]; NIGMS NIH HHS [R01 GM056203] NR 15 TC 21 Z9 21 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2009 VL 27 IS 10 BP 916 EP 917 DI 10.1038/nbt1009-916 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 515LO UT WOS:000271472500020 PM 19816448 ER PT J AU Kubota, K Anjum, R Yu, YH Kunz, RC Andersen, JN Kraus, M Keilhack, H Nagashima, K Krauss, S Paweletz, C Hendrickson, RC Feldman, AS Wu, CL Rush, J Villen, J Gygi, SP AF Kubota, Kazuishi Anjum, Rana Yu, Yonghao Kunz, Ryan C. Andersen, Jannik N. Kraus, Manfred Keilhack, Heike Nagashima, Kumiko Krauss, Stefan Paweletz, Cloud Hendrickson, Ronald C. Feldman, Adam S. Wu, Chin-Lee Rush, John Villen, Judit Gygi, Steven P. TI Sensitive multiplexed analysis of kinase activities and activity-based kinase identification SO NATURE BIOTECHNOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; MASS-SPECTROMETRY; DRUG DISCOVERY; PHOSPHORYLATION ANALYSIS; PHOSPHOPROTEOME ANALYSIS; SIGNALING NETWORKS; IN-VIVO; SUBSTRATE; CANCER; PEPTIDES AB Constitutive activation of one or more kinase signaling pathways is a hallmark of many cancers. Here we extend the previously described mass spectrometry-based KAYAK approach by monitoring kinase activities from multiple signaling pathways simultaneously. This improved single-reaction strategy, which quantifies the phosphorylation of 90 synthetic peptides in a single mass spectrometry run, is compatible with nanogram to microgram amounts of cell lysate. Furthermore, the approach enhances kinase monospecificity through substrate competition effects, faithfully reporting the signatures of many signaling pathways after mitogen stimulation or of basal pathway activation differences across a panel of well-studied cancer cell lines. Hierarchical clustering of activities from related experiments groups peptides phosphorylated by similar kinases together and, when combined with pathway alteration using pharmacological inhibitors, distinguishes underlying differences in potency, off-target effects and genetic backgrounds. Finally, we introduce a strategy to identify the kinase, and even associated protein complex members, responsible for phosphorylation events of interest. C1 [Kubota, Kazuishi; Anjum, Rana; Yu, Yonghao; Kunz, Ryan C.; Villen, Judit; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Andersen, Jannik N.; Kraus, Manfred; Keilhack, Heike; Nagashima, Kumiko; Krauss, Stefan; Paweletz, Cloud] Merck Res Labs, Boston, MA USA. [Hendrickson, Ronald C.] Merck & Co Inc, Rahway, NJ 07065 USA. [Feldman, Adam S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rush, John] Cell Signaling Technol, Danvers, MA USA. RP Gygi, SP (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM steven_gygi@hms.harvard.edu OI Andersen, Jannik/0000-0003-4528-2120; Villen, Judit/0000-0002-1005-1739 FU National Institutes of Health (NIH) [HG3456, GM67945, GM51405]; Merck and ThermoFisher; Daiichi Sankyo Co., Ltd; Spanish Ministry of Education and Science FX This work was supported in part by grants from the National Institutes of Health (NIH; HG3456 and GM67945) and an industry-sponsored research project to S. P. G. from Merck and ThermoFisher. K. K. was supported by Daiichi Sankyo Co., Ltd. Y.Y. was partly supported by J. Blenis through grants from the NIH (GM51405). J. V. was supported by a grant from the Spanish Ministry of Education and Science. We thank C. Zhou, S. Elledge and N. Dephoure for help with cell cycle sample preparation, J. Elias and D. Kolippakkam for bioinformatics support, M. Rodriguez-Falcon for establishing Stagetip-IMAC protocol, and S. Sando and T. Robbins for peptide purification. We appreciate the advice and encouragement of many members of the Gygi lab and Mayumi Kubota. NR 59 TC 59 Z9 60 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2009 VL 27 IS 10 BP 933 EP U98 DI 10.1038/nbt.1566 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 515LO UT WOS:000271472500024 PM 19801977 ER PT J AU Ferrandon, S Feinstein, TN Castro, M Wang, B Bouley, R Potts, JT Gardella, TJ Vilardaga, JP AF Ferrandon, Sebastien Feinstein, Timothy N. Castro, Marian Wang, Bin Bouley, Richard Potts, John T. Gardella, Thomas J. Vilardaga, Jean-Pierre TI Sustained cyclic AMP production by parathyroid hormone receptor endocytosis SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; LIVING CELLS; ACTIVATION; PHOTOTRANSDUCTION; CONFORMATIONS; TRAFFICKING; SELECTIVITY; INFUSION; KINETICS; BINDING AB Cell signaling mediated by the G protein-coupled parathyroid hormone receptor type 1 (PTHR) is fundamental to bone and kidney physiology. It has been unclear how the two ligand systems-PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine-can effectively operate with only one receptor and trigger different durations of the cAMP responses. Here we analyze the ligand response by measuring the kinetics of activation and deactivation for each individual reaction step along the PTHR signaling cascade. We found that during the time frame of G protein coupling and cAMP production, PTHrP(1-36) action was restricted to the cell surface, whereas PTH(1-34) had moved to internalized compartments where it remained associated with the PTHR and G alpha(s), potentially as a persistent and active ternary complex. Such marked differences suggest a mechanism by which PTH and PTHrP induce differential responses, and these results indicate that the central tenet that cAMP production originates exclusively at the cell membrane must be revised. C1 [Ferrandon, Sebastien; Castro, Marian; Potts, John T.; Gardella, Thomas J.; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Endocrine Unit, Boston, MA 02114 USA. [Ferrandon, Sebastien; Bouley, Richard; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Ferrandon, Sebastien; Castro, Marian; Potts, John T.; Gardella, Thomas J.; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Endocrine Unit, Boston, MA 02114 USA. [Ferrandon, Sebastien; Bouley, Richard; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Feinstein, Timothy N.; Wang, Bin; Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. RP Vilardaga, JP (reprint author), Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Endocrine Unit, Boston, MA 02114 USA. EM jpv@pitt.edu RI Feinstein, Timothy/G-3110-2011; Castro, Marian/K-5747-2014; OI Castro, Marian/0000-0002-4732-1966; Feinstein, Timothy/0000-0002-9801-9708; Wang, Bin/0000-0002-5396-6111 FU Department of Medicine, Massachusetts General Hospital; Department of Pharmacology and Chemical Biology, University of Pittsburgh; Xunta de Galicia (Spain); US National Institutes of Health [DK38451]; National Kidney Foundation FX J.-P. V. thanks M. J. Lohse (University of Wuerzburg) and N.O. Nikolaev (University of Wuerzburg) for generously sharing their plasmid encoding Epac-CFP/YFP, C. Berlot (Weis Center for Research) for the plasmid encoding G alphas-CFP, M. Buemann (University of Wuerzburg) for the G gamma2-CFP construct and A. Bisello (University of Pittsburgh) for Dyn K44A. The authors thank D. Altschuler for the use of his FRET imaging microscope. This work was supported by start-up funds from the Department of Medicine, Massachusetts General Hospital, and the Department of Pharmacology and Chemical Biology, University of Pittsburgh (to J.-P. V.). M. C. is at the Department of Pharmacology, School of Pharmacy, University of Santiago de Compostella (Spain) and received a fellowship from the Xunta de Galicia (Spain) for a research sabbatical at the J.-P. V. laboratory at the Endocrine Unit of the Massachusetts General Hospital. R. B. was supported by US National Institutes of Health grant DK38451 and received an investigator award from the National Kidney Foundation. J.-P. V. thanks P. Friedman and G. Romero for critically commenting on the manuscript. NR 22 TC 174 Z9 174 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD OCT PY 2009 VL 5 IS 10 BP 734 EP 742 DI 10.1038/nchembio.206 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497EV UT WOS:000270039900011 PM 19701185 ER PT J AU van Es, MA Veldink, JH Saris, CGJ Blauw, HM van Vught, PWJ Birve, A Lemmens, R Schelhaas, HJ Groen, EJN Huisman, MHB van der Kooi, AJ de Visser, M Dahlberg, C Estrada, K Rivadeneira, F Hofman, A Zwarts, MJ van Doormaal, PTC Rujescu, D Strengman, E Giegling, I Muglia, P Tomik, B Slowik, A Uitterlinden, AG Hendrich, C Waibel, S Meyer, T Ludolph, AC Glass, JD Purcell, S Cichon, S Nothen, MM Wichmann, HE Schreiber, S Vermeulen, SHHM Kiemeney, LA Wokke, JHJ Cronin, S McLaughlin, RL Hardiman, O Fumoto, K Pasterkamp, RJ Meininger, V Melki, J Leigh, PN Shaw, CE Landers, JE Al-Chalabi, A Brown, RH Robberecht, W Andersen, PM Ophoff, RA van den Berg, LH AF van Es, Michael A. Veldink, Jan H. Saris, Christiaan G. J. Blauw, Hylke M. van Vught, Paul W. J. Birve, Anna Lemmens, Robin Schelhaas, Helenius J. Groen, Ewout J. N. Huisman, Mark H. B. van der Kooi, Anneke J. de Visser, Marianne Dahlberg, Caroline Estrada, Karol Rivadeneira, Fernando Hofman, Albert Zwarts, Machiel J. van Doormaal, Perry T. C. Rujescu, Dan Strengman, Eric Giegling, Ina Muglia, Pierandrea Tomik, Barbara Slowik, Agnieszka Uitterlinden, Andre G. Hendrich, Corinna Waibel, Stefan Meyer, Thomas Ludolph, Albert C. Glass, Jonathan D. Purcell, Shaun Cichon, Sven Noethen, Markus M. Wichmann, H-Erich Schreiber, Stefan Vermeulen, Sita H. H. M. Kiemeney, Lambertus A. Wokke, John H. J. Cronin, Simon McLaughlin, Russell L. Hardiman, Orla Fumoto, Katsumi Pasterkamp, R. Jeroen Meininger, Vincent Melki, Judith Leigh, P. Nigel Shaw, Christopher E. Landers, John E. Al-Chalabi, Ammar Brown, Robert H., Jr. Robberecht, Wim Andersen, Peter M. Ophoff, Roel A. van den Berg, Leonard H. TI Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis SO NATURE GENETICS LA English DT Article ID FRONTOTEMPORAL DEMENTIA; CONFERS SUSCEPTIBILITY; CHROMOSOME 9P; POPULATION; DISEASE; VARIANTS; RELEASE; LINKAGE; HAPMAP; DESIGN AB We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees. C1 [Wokke, John H. J.; van den Berg, Leonard H.] Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Birve, Anna; Dahlberg, Caroline; Andersen, Peter M.] Umea Univ Hosp, Inst Clin Neurosci, S-90185 Umea, Sweden. [Lemmens, Robin; Robberecht, Wim] Katholieke Univ Leuven VIB, Vesalius Res Ctr, Leuven, Belgium. [Lemmens, Robin; Robberecht, Wim] Univ Leuven, Dept Neurol, Univ Hosp Leuven, Louvain, Belgium. [Schelhaas, Helenius J.; Zwarts, Machiel J.] Radboud Univ Nijmegen, Dept Neurology Clin Neurophysiol, Donders Inst Brain Cognit & Behav, Ctr Neurosci,Med Ctr, NL-6525 ED Nijmegen, Netherlands. [van der Kooi, Anneke J.; de Visser, Marianne] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Estrada, Karol; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Genet Lab, Rotterdam, Netherlands. [Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Rujescu, Dan; Giegling, Ina] Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-8000 Munich, Germany. [Strengman, Eric; Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Strengman, Eric; Ophoff, Roel A.] Univ Med Ctr Utrecht, Rudolf Magnus Inst, Utrecht, Netherlands. [Muglia, Pierandrea] GlaxoSmithKline R&D, Med Genet, Verona, Italy. [Tomik, Barbara; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, Krakow, Poland. [Hendrich, Corinna; Waibel, Stefan; Ludolph, Albert C.] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. [Meyer, Thomas] Humboldt Univ, Dept Neurol, Charite Univ Hosp, Berlin, Germany. [Glass, Jonathan D.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Cichon, Sven; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Cichon, Sven; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Wichmann, H-Erich] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Schreiber, Stefan] Univ Kiel, Dept Gen Internal Med, Kiel, Germany. [Vermeulen, Sita H. H. M.] Radboud Univ Nijmegen, Dept Epidemiol Biostat & HTA, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Dept Urol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Comprehens Canc Ctr E, Nijmegen, Netherlands. [Cronin, Simon] Royal Coll Surgeons Ireland, Dept Clin Neurol Sci, Dublin 2, Ireland. [Cronin, Simon; McLaughlin, Russell L.; Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [McLaughlin, Russell L.; Hardiman, Orla] Trinity Coll Dublin, Inst Neurosci, Dublin, Ireland. [Fumoto, Katsumi; Pasterkamp, R. Jeroen] Univ Med Ctr Utrecht, Dept Neurosci & Pharmacol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Meininger, Vincent] Hop La Pitie Salpetriere, Dept Neurol, AP HP, Paris, France. [Melki, Judith] Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel. [Leigh, P. Nigel; Shaw, Christopher E.; Al-Chalabi, Ammar] Kings Coll London, Dept Clin Neurosci, MRC, Ctr Neurodegenerat Res,Inst Psychiat, London WC2R 2LS, England. [Landers, John E.; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Landers, John E.; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. RP van den Berg, LH (reprint author), Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. EM R.A.Ophoff@umcutrecht.nl; L.H.vandenBerg@umcutrecht.nl RI Schreiber, Stefan/B-6748-2008; Kiemeney, Lambertus/D-3357-2009; Saris, C.G.J./L-4623-2015; Rivadeneira, Fernando/O-5385-2015; Vermeulen, H.H.M./L-4716-2015; Groen, Ewout/L-5081-2016; Al-Chalabi, Ammar/E-5361-2010; Schelhaas, Helenius Jurgen/E-2815-2010; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; OI Schreiber, Stefan/0000-0003-2254-7771; Kiemeney, Lambertus/0000-0002-2368-1326; Rivadeneira, Fernando/0000-0001-9435-9441; Groen, Ewout/0000-0002-2330-9444; Ingre, Caroline/0000-0001-5327-7204; Pasterkamp, Jeroen/0000-0003-1631-6440; Al-Chalabi, Ammar/0000-0002-4924-7712; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Nothen, Markus/0000-0002-8770-2464; Hardiman, Orla/0000-0003-2610-1291; McLaughlin, Russell/0000-0003-3915-2135 FU Prinses Beatrix Fonds; VSB fonds; Kersten Foundation; Netherlands ALS Foundation; Adessium Foundation; Brain Foundation of The Netherlands; Netherlands Organisation for Scientific Research (NWO) investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93015]; Netherlands Genomics Initiative/NWO [050-060-810]; National Institute for Mental Health (R.A.O.); Erasmus Medical Center; Erasmus University, Rotterdam; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission; Municipality of Rotterdam; Muscular Dystrophy Association USA; Health Research Board of Ireland; Irish Motor Neuron Disease Research Foundation; Swedish Brain Research Foundation; Hallstens Research Foundation; Swedish Medical Society; Bjorklund Foundation for ALS Research; Swedish Association for the Neurologically; Belgian Federal Science Policy Office; Polish Ministry of Science and Higher Education [N N402 083934, N402 092 32/3216]; Association pour la Recherche sur la SLA; Association Reseau SLA Ile de France; Motor Neurone Disease Association of Great Britain and Ireland; Medical Research Council (UK); Wellcome Trust; Psychiatry Research Trust; ALS Therapy Alliance; Angel Fund; ALS Research Foundation; Al-Athel ALS Research Foundation; ALS Family Charitable Foundation; National Institute of Neurological Disorders and Stroke [NS050557] FX We thank the individuals and their families who participated in this project; the study staff, general practitioners and pharmacists; P. Arp, M. Jhamai, M. Moorhouse, M. Verkerk and S. Bervoets for their help in creating the GWAS database; D. B. Goldstein for his contribution to the genotyping and analysis of the control sample from the German schizophrenia study; and N. Freimer for critical comments and reading of the manuscript. This project was supported by the Prinses Beatrix Fonds, VSB fonds, H. Kersten and M. Kersten (Kersten Foundation), The Netherlands ALS Foundation, and J. R. van Dijk and the Adessium Foundation (L.H.v.d.B.). J. H. V. was supported by the Brain Foundation of The Netherlands. The generation and management of GWAS genotype data for the Rotterdam Study was supported by The Netherlands Organisation for Scientific Research (NWO) investments (no. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (RIDE; 014-93015)and the Netherlands Genomics Initiative/NWO (project no. 050-060-810). The controls from the Dutch schizophrenia GWAS were genotyped with the support of the National Institute for Mental Health (R.A.O.). The Rotterdam study was funded by Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands Organization for Health Research and Development; RIDE; the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The Irish studies were funded by the Muscular Dystrophy Association USA (S. C., O.H.), the Health Research Board of Ireland (O.H.) and the Irish Motor Neuron Disease Research Foundation. In Sweden, this project was supported by the Swedish Brain Research Foundation, the Hallstens Research Foundation, the Swedish Medical Society, the Bjorklund Foundation for ALS Research and the Swedish Association for the Neurologically Disabled (P. M. A.). W. R. was supported through the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders and by the Interuniversity Attraction Poles program P6/43 of the Belgian Federal Science Policy Office. The Polish study was partially funded by the Polish Ministry of Science and Higher Education (nos. N N402 083934 and N402 092 32/3216). In France, this study was funded by the Association pour la Recherche sur la SLA and the Association Reseau SLA Ile de France. We thank the Motor Neurone Disease Association of Great Britain and Ireland, the Medical Research Council (UK), the Wellcome Trust and the Psychiatry Research Trust (Tim Perkins Fund and Charcot Fund). Support was also provided by the ALS Therapy Alliance, Project ALS, the Angel Fund, the Pierre L. de Bourgknecht ALS Research Foundation, the Al-Athel ALS Research Foundation, the ALS Family Charitable Foundation and the National Institute of Neurological Disorders and Stroke (NS050557). R. H. B. is a cofounder of AviTx, which targets development of therapies. NR 33 TC 167 Z9 170 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2009 VL 41 IS 10 BP 1083 EP U53 DI 10.1038/ng.442 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 500UG UT WOS:000270330400010 PM 19734901 ER PT J AU Mandal, M Powers, SE Ochiai, K Georgopoulos, K Kee, BL Singh, H Clark, MR AF Mandal, Malay Powers, Sarah E. Ochiai, Kyoko Georgopoulos, Katia Kee, Barbara L. Singh, Harinder Clark, Marcus R. TI Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN HEAVY-CHAIN; TRANSCRIPTION FACTOR; GENE REARRANGEMENTS; ACTIVATED RAS; KAPPA LOCUS; PRE-BCR; RECEPTOR; PROTEINS; STAGE; E2A AB Signals through the pre-B cell antigen receptor (pre-BCR) and interleukin 7 receptor (IL-7R) coordinate pre-B cell population expansion with subsequent recombination of the locus encoding immunoglobulin kappa-chain (Igk). Although many 'downstream' effectors of each receptor are known, how they integrate to mediate development has remained unclear. Here we report that pre-BCR-mediated activation of the Ras-MEK-Erk signaling pathway silenced transcription of Ccnd3 (encoding cyclin D3) and coordinated exit from the cell cycle with induction of the transcription factor E2A and the initiation of Igk recombination. IL-7R-mediated activation of the transcription factor STAT5 opposed this pathway by promoting Ccnd3 expression and concomitantly inhibiting Igk transcription by binding to the Igk intronic enhancer and preventing E2A recruitment. Our data show how pre-BCR signaling poises pre-B cells to undergo differentiation after escape from IL-7R signaling. C1 [Mandal, Malay; Powers, Sarah E.; Clark, Marcus R.] Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA. [Ochiai, Kyoko; Singh, Harinder] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. [Georgopoulos, Katia] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. [Kee, Barbara L.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Clark, MR (reprint author), Univ Chicago, Dept Med, Rheumatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM mclark@medicine.bsd.uchicago.edu OI Powers, Sarah/0000-0002-6812-4312 FU NIGMS NIH HHS [R01 GM067772, R01 GM052736, R01 GM088847, R01 GM052736-10, R01 GM052736-11, R01 GM067772-04S1, R01 GM088847-01A2, R01 GM067772-04] NR 45 TC 62 Z9 63 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2009 VL 10 IS 10 BP 1110 EP U91 DI 10.1038/ni.1785 PG 9 WC Immunology SC Immunology GA 496VG UT WOS:000270006900015 PM 19734904 ER PT J AU Plum, L Lin, HV Dutia, R Tanaka, J Aizawa, KS Matsumoto, M Kim, AJ Cawley, NX Paik, JH Loh, YP DePinho, RA Wardlaw, SL Accili, D AF Plum, Leona Lin, Hua V. Dutia, Roxanne Tanaka, Jun Aizawa, Kumiko S. Matsumoto, Michihiro Kim, Andrea J. Cawley, Niamh X. Paik, Ji-Hye Loh, Y. Peng DePinho, Ronald A. Wardlaw, Sharon L. Accili, Domenico TI The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake SO NATURE MEDICINE LA English DT Article ID PROTHYROTROPIN-RELEASING HORMONE; PROHORMONE CONVERTASES; BETA-ENDORPHIN; BODY-WEIGHT; CPE(FAT)/CPE(FAT) MICE; STIMULATING HORMONE; ENERGY HOMEOSTASIS; LEPTIN; PEPTIDE; INSULIN AB Reduced food intake brings about an adaptive decrease in energy expenditure that contributes to the recidivism of obesity after weight loss. Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyt-estimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. This neuropeptide profile is associated with decreased food intake and normal energy expenditure in Pomc-Foxo1(-/-) mice. We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. The dissociation of food intake from energy expenditure in Pomc-Foxo1(-/-) mice represents a model for therapeutic intervention in obesity and raises the possibility of targeting Cpe to develop weight loss medications. C1 [Plum, Leona; Lin, Hua V.; Dutia, Roxanne; Tanaka, Jun; Aizawa, Kumiko S.; Matsumoto, Michihiro; Kim, Andrea J.; Wardlaw, Sharon L.; Accili, Domenico] Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10027 USA. [Plum, Leona; Lin, Hua V.; Dutia, Roxanne; Tanaka, Jun; Aizawa, Kumiko S.; Matsumoto, Michihiro; Kim, Andrea J.; Wardlaw, Sharon L.; Accili, Domenico] Columbia Univ, Dept Med, New York, NY USA. [Matsumoto, Michihiro] Int Med Ctr Japan, Dept Clin Pharmacol, Tokyo, Japan. [Cawley, Niamh X.; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, Cellular Neurobiol Sect, Bethesda, MD USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Accili, D (reprint author), Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10027 USA. EM da230@columbia.edu FU Deutsche Forschungsgemeinschaft [PL542/1-1]; US National Institutes of Health [DK57539, DK58282, DK80003, DK63608]; Robert A. and Renee E. Belfer Family Institute for Innovative Cancer Science FX Supported by Deutsche Forschungsgemeinschaft PL542/1-1 (L.P.), US National Institutes of Health DK57539 and DK58282 (D.A.), DK80003 (S.L.W.) and DK63608 (Columbia Diabetes and Endocrinology Research Center). We thank R. Leibel for insightful discussions, L. Zeltser and S. Padilla for help with in situ hybridization, N. Seidah (Clinical Research Institute of Montreal) and D. Good (University of Massachusetts) for plasmids encoding pCsk1, A. White (University of Manchester) for neuropeptide antisera, and M. Low (Oregon Health Sciences University) for Pomc-Gfp transgenic mice, Y. Liu for technical assistance and members of the Accili and Wardlaw laboratories for stimulating discussions. R.A.D. is an American Cancer Society Research Professor and an Ellison Medical Foundation Senior Scholar and is supported by the Robert A. and Renee E. Belfer Family Institute for Innovative Cancer Science. NR 55 TC 78 Z9 80 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2009 VL 15 IS 10 BP 1195 EP U125 DI 10.1038/nm.2026 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 504EC UT WOS:000270596400032 PM 19767734 ER PT J AU Vakoc, BJ Lanning, RM Tyrrell, JA Padera, TP Bartlett, LA Stylianopoulos, T Munn, LL Tearney, GJ Fukumura, D Jain, RK Bouma, BE AF Vakoc, Benjamin J. Lanning, Ryan M. Tyrrell, James A. Padera, Timothy P. Bartlett, Lisa A. Stylianopoulos, Triantafyllos Munn, Lance L. Tearney, Guillermo J. Fukumura, Dai Jain, Rakesh K. Bouma, Brett E. TI Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging SO NATURE MEDICINE LA English DT Article ID COHERENCE TOMOGRAPHY; LYMPHATIC METASTASIS; GROWTH; ANGIOGENESIS; VASCULATURE; FLOW; NORMALIZATION; ARCHITECTURE; SENSITIVITY; PRESSURE AB Intravital multiphoton microscopy has provided powerful mechanistic insights into health and disease and has become a common instrument in the modern biological laboratory. The requisite high numerical aperture and exogenous contrast agents that enable multiphoton microscopy, however, limit the ability to investigate substantial tissue volumes or to probe dynamic changes repeatedly over prolonged periods. Here we introduce optical frequency domain imaging (OFDI) as an intravital microscopy that circumvents the technical limitations of multiphoton microscopy and, as a result, provides unprecedented access to previously unexplored, crucial aspects of tissue biology. Using unique OFDI-based approaches and entirely intrinsic mechanisms of contrast, we present rapid and repeated measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy, thereby demonstrating the potential of OFDI to facilitate the exploration of physiological and pathological processes and the evaluation of treatment strategies. C1 [Lanning, Ryan M.; Tyrrell, James A.; Padera, Timothy P.; Stylianopoulos, Triantafyllos; Munn, Lance L.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Vakoc, Benjamin J.; Bartlett, Lisa A.; Tearney, Guillermo J.; Bouma, Brett E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Vakoc, Benjamin J.; Lanning, Ryan M.; Tearney, Guillermo J.; Bouma, Brett E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu; bouma@helix.mgh.harvard.edu RI Tyrrell, James/A-6359-2010; Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Stylianopoulos, Triantafyllos/0000-0002-3093-1696; Padera, Timothy/0000-0002-3453-9384 FU US National Institutes of Health [P01-CA080124, R01-CA085140, R01-CA115767, R01 CA126642, R33-CA125560, K25-CA127465, K99-CA137167, R01-CA096915]; US Department of Defense Breast Cancer Research Program fellowship [W81XWH-06-1-0436] FX We thank J. Baish for insightful input regarding fractal analysis. We also thank J. Kahn and S. Roberge for preparation of animal models, P. Huang for animal care and colony maintenance, and E. di Tomaso and C. Smith for histological preparations. We thank Genentech for supplying the MDA-MB-361HK mammary carcinoma cells and J. B. Little of the Harvard School for Public Health for HSTS26T. This research was funded in part by US National Institutes of Health grants P01-CA080124, R01-CA085140, R01-CA115767, R01 CA126642, R33-CA125560, K25-CA127465, K99-CA137167, and R01-CA096915. R.M.L. is supported in part by US Department of Defense Breast Cancer Research Program fellowship W81XWH-06-1-0436. NR 28 TC 291 Z9 294 U1 3 U2 59 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2009 VL 15 IS 10 BP 1219 EP U151 DI 10.1038/nm.1971 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 504EC UT WOS:000270596400036 PM 19749772 ER PT J AU Azim, E Jabaudon, D Fame, RM Macklis, JD AF Azim, Eiman Jabaudon, Denis Fame, Ryann M. Macklis, Jeffrey D. TI SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development SO NATURE NEUROSCIENCE LA English DT Article ID RAT OCCIPITAL CORTEX; CEREBRAL-CORTEX; CORTICAL INTERNEURONS; IMMUNOREACTIVE NEURONS; MOUSE TELENCEPHALON; GENE SOX6; SPECIFICATION; EXPRESSION; MIGRATION; SUBTYPE AB The neuronal diversity of the CNS emerges largely from controlled spatial and temporal segregation of cell type-specific molecular regulators. We found that the transcription factor SOX6 controls the molecular segregation of dorsal (pallial) from ventral (subpallial) telencephalic progenitors and the differentiation of cortical interneurons, regulating forebrain progenitor and interneuron heterogeneity. During corticogenesis in mice, SOX6 and SOX5 were largely mutually exclusively expressed in pallial and subpallial progenitors, respectively, and remained mutually exclusive in a reverse pattern in postmitotic neuronal progeny. Loss of SOX6 from pallial progenitors caused their inappropriate expression of normally subpallium-restricted developmental controls, conferring mixed dorsal-ventral identity. In postmitotic cortical interneurons, loss of SOX6 disrupted the differentiation and diversity of cortical interneuron subtypes, analogous to SOX5 control over cortical projection neuron development. These data indicate that SOX6 is a central regulator of both progenitor and cortical interneuron diversity during neocortical development. C1 [Azim, Eiman; Jabaudon, Denis; Fame, Ryann M.; Macklis, Jeffrey D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Neurosci, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02115 USA. [Azim, Eiman; Jabaudon, Denis; Fame, Ryann M.; Macklis, Jeffrey D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Neurosci, Ctr Nervous Syst Repair,Dept Neurol, Boston, MA USA. [Azim, Eiman; Jabaudon, Denis; Fame, Ryann M.; Macklis, Jeffrey D.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA. [Azim, Eiman; Jabaudon, Denis; Fame, Ryann M.; Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Azim, Eiman; Jabaudon, Denis; Fame, Ryann M.; Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Fame, Ryann M.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Neurosci, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02115 USA. EM jeffrey_macklis@hms.harvard.edu OI Fame, Ryann/0000-0002-8244-2624; Azim, Eiman/0000-0002-1015-1772; Jabaudon, Denis/0000-0003-2438-4769 FU US National Institutes of Health [NS49553, NS45523, NS41590, F31 NS060421]; Travis Roy Foundation; Spastic Paraplegia Foundation; Massachusetts Spinal Cord Injury research program; Harvard Stem Cell Institute; Swiss National Science Foundation; Holcim Foundation; National Science Foundation Graduate Research Fellowship FX We thank K. Billmers, A. Palmer, L. Pasquina, K. Quinn, D. Schuback, E. Sievert, A. Wheeler and T. Yamamoto for superb technical assistance, G. Fishell, R. BatistaBrito, G. Miyoshi, P. Arlotta, B. Molyneaux, H. Padmanabhan, F. Guillemot, Q. Ma, C. Cepko and L. Goodrich for helpful discussions and input, U. Berger for technical assistance with in situ hybridization, C. Lois, R. Hevner, V. Lefebvre, F. Guillemot, V. Pachnis and Y. Yanagawa for generously sharing mice, antibodies and reagents, and current and past members of our laboratory for helpful suggestions. This work was partially supported by grants from the US National Institutes of Health ( NS49553 and NS45523; additional infrastructure supported by NS41590), the Travis Roy Foundation, the Spastic Paraplegia Foundation, the Massachusetts Spinal Cord Injury research program, and the Harvard Stem Cell Institute to J. D. M., and by the Jane and Lee Seidman Fund for CNS Research, and the Emily and Robert Pearlstein Fund for Nervous System Repair. E. A. was partially supported by a US National Institutes of Health individual predoctoral National Research Service Award fellowship ( F31 NS060421). D. J. was partially supported by fellowships from the Swiss National Science Foundation and the Holcim Foundation. R. M. F. was partially supported by a National Science Foundation Graduate Research Fellowship. NR 49 TC 89 Z9 91 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2009 VL 12 IS 10 BP 1238 EP U51 DI 10.1038/nn.2387 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 498US UT WOS:000270170200012 PM 19657336 ER PT J AU de Nijs, L Leon, C Nguyen, L LoTurco, JJ Delgado-Escueta, AV Grisar, T Lakaye, B AF de Nijs, Laurence Leon, Christine Nguyen, Laurent LoTurco, Joseph J. Delgado-Escueta, Antonio V. Grisar, Thierry Lakaye, Bernard TI EFHC1 interacts with microtubules to regulate cell division and cortical development SO NATURE NEUROSCIENCE LA English DT Article ID JUVENILE MYOCLONIC EPILEPSY; NEURONAL MIGRATION; RNA INTERFERENCE; MITOTIC SPINDLE; CEREBRAL-CORTEX; GENERALIZED EPILEPSY; CYTOPLASMIC DYNEIN; NEOCORTEX; MUTATIONS; PROTEIN AB Mutations in the EFHC1 gene are linked to juvenile myoclonic epilepsy (JME), one of the most frequent forms of idiopathic generalized epilepsies. JME is associated with subtle alterations of cortical and subcortical architecture, but the underlying pathological mechanism remains unknown. We found that EFHC1 is a microtubule-associated protein involved in the regulation of cell division. In vitro, EFHC1 loss of function disrupted mitotic spindle organization, impaired M phase progression, induced microtubule bundling and increased apoptosis. EFHC1 impairment in the rat developing neocortex by ex vivo and in utero electroporation caused a marked disruption of radial migration. We found that this effect was a result of cortical progenitors failing to exit the cell cycle and defects in the radial glia scaffold organization and in the locomotion of postmitotic neurons. Therefore, we propose that EFHC1 is a regulator of cell division and neuronal migration during cortical development and that disruption of its functions leads to JME. C1 [de Nijs, Laurence; Leon, Christine; Nguyen, Laurent; Grisar, Thierry; Lakaye, Bernard] Univ Liege, GIGA Neurosci, Liege, Belgium. [LoTurco, Joseph J.] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 USA. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Epilepsy Genet Genom Labs, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Grisar, T (reprint author), Univ Liege, GIGA Neurosci, Liege, Belgium. EM tgrisar@ulg.ac.be OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU FNRS (Fonds de la Recherche Scientifique Medicale) [3.4565.03]; Leon Fredericq Foundation FX We thank B. Coumans for skillful technical assistance, J. Bai for help with in utero electroporation processing and S. Ormenese from the GIGA-Imaging and Flow Cytometry platform for support with flow cytometry. We are also grateful to A. Adamantidis for critical reading of the manuscript. We thank F. Polleux for the NeuroD-IRES-GFP plasmid. This work was supported by grants from the F. R. S.- FNRS (Fonds de la Recherche Scientifique Medicale 3.4565.03 to T. G. and B. L.) and the Leon Fredericq Foundation (to L. d. N.). L. N. and B. L. are research associates at the F. R. S.- FNRS. NR 50 TC 37 Z9 37 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2009 VL 12 IS 10 BP 1266 EP U84 DI 10.1038/nn.2390 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 498US UT WOS:000270170200015 PM 19734894 ER PT J AU Laubach, JP Richardson, PG Anderson, KC AF Laubach, Jacob P. Richardson, Paul G. Anderson, Kenneth C. TI Thalidomide maintenance in multiple myeloma SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID CELL TRANSPLANTATION; THERAPY; TRIAL; ANGIOGENESIS; PREDNISONE; SURVIVAL C1 [Laubach, Jacob P.; Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Laubach, JP (reprint author), Harvard Univ, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu NR 10 TC 4 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD OCT PY 2009 VL 6 IS 10 BP 565 EP 566 DI 10.1038/nrclinonc.2009.131 PG 2 WC Oncology SC Oncology GA 498SP UT WOS:000270163800006 PM 19787000 ER PT J AU Nelson, EJ Harris, JB Morris, JG Calderwood, SB Camilli, A AF Nelson, Eric J. Harris, Jason B. Morris, J. Glenn, Jr. Calderwood, Stephen B. Camilli, Andrew TI Cholera transmission: the host, pathogen and bacteriophage dynamic SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID CLASSICAL CTX PROPHAGE; VIBRIO-CHOLERAE; RURAL BANGLADESH; BLOOD-GROUP; INTESTINAL COLONIZATION; AQUATIC ENVIRONMENT; INFECTIOUS-DISEASE; SEASONAL CHOLERA; ENDEMIC CHOLERA; FAMILY CONTACTS AB Zimbabwe offers the most recent example of the tragedy that befalls a country and its people when cholera strikes. The 2008-2009 outbreak rapidly spread across every province and brought rates of mortality similar to those witnessed as a consequence of cholera infections a hundred years ago. In this Review we highlight the advances that will help to unravel how interactions between the host, the bacterial pathogen and the lytic bacteriophage might propel and quench cholera outbreaks in endemic settings and in emergent epidemic regions such as Zimbabwe. C1 [Nelson, Eric J.; Camilli, Andrew] Howard Hughes Med Inst, Boston, MA 02111 USA. [Nelson, Eric J.; Camilli, Andrew] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Harris, Jason B.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Morris, J. Glenn, Jr.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. RP Camilli, A (reprint author), Howard Hughes Med Inst, Boston, MA 02111 USA. EM Andrew.camilli@tufts.edu FU National Institutes of Health [R01 AI045746, R01 AI055058] FX A.C. is supported by the National Institutes of Health grants R01 AI045746 and R01 AI055058 NR 118 TC 152 Z9 156 U1 10 U2 79 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD OCT PY 2009 VL 7 IS 10 BP 693 EP 702 DI 10.1038/nrmicro2204 PG 10 WC Microbiology SC Microbiology GA 494QU UT WOS:000269831000014 PM 19756008 ER PT J AU Simon, JA Kingston, RE AF Simon, Jeffrey A. Kingston, Robert E. TI Mechanisms of Polycomb gene silencing: knowns and unknowns SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID RNA-POLYMERASE-II; HISTONE METHYLTRANSFERASE ACTIVITY; EMBRYONIC STEM-CELLS; POLYCOMB/TRITHORAX RESPONSE ELEMENTS; TRITHORAX GROUP PROTEINS; DROSOPHILA-MELANOGASTER; BITHORAX COMPLEX; HOMEOTIC GENE; H2A UBIQUITINATION; STRUCTURAL BASIS AB Polycomb proteins form chromatin-modifying complexes that implement transcriptional silencing in higher eukaryotes. Hundreds of genes are silenced by Polycomb proteins, including dozens of genes that encode crucial developmental regulators in organisms ranging from plants to humans. Two main families of complexes, called Polycomb repressive complex 1 (PRC1) and PRC2, are targeted to repressed regions. Recent studies have advanced our understanding of these complexes, including their potential mechanisms of gene silencing, the roles of chromatin modifications, their means of delivery to target genes and the functional distinctions among variant complexes. Emerging concepts include the existence of a Polycomb barrier to transcription elongation and the involvement of non-coding RNAs in the targeting of Polycomb complexes. These findings have an impact on the epigenetic programming of gene expression in many biological systems. C1 [Simon, Jeffrey A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Simon, JA (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. EM simon004@umn.edu; kingston@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R37 GM048405, R01 GM043901] NR 171 TC 701 Z9 714 U1 16 U2 122 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD OCT PY 2009 VL 10 IS 10 BP 697 EP 708 DI 10.1038/nrm2763 PG 12 WC Cell Biology SC Cell Biology GA 497EW UT WOS:000270040300012 PM 19738629 ER PT J AU Siegel, JM AF Siegel, Jerome M. TI SLEEP - OPINION Sleep viewed as a state of adaptive inactivity SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID EYE-MOVEMENT SLEEP; SLOW-WAVE SLEEP; CONTINUOUS AUDITORY VIGILANCE; CEREBRAL GLUCOSE-UTILIZATION; LIZARD CTENOSAURA-PECTINATA; MAMMALIAN SLEEP; REM-SLEEP; PHYLOGENETIC ANALYSIS; PARADOXICAL SLEEP; GROWTH-HORMONE AB Sleep is often viewed as a vulnerable state that is incompatible with behaviours that nourish and propagate species. This has led to the hypothesis that sleep has survived because it fulfills some universal, but as yet unknown, vital function. I propose that sleep is best understood as a variant of dormant states seen throughout the plant and animal kingdoms and that it is itself highly adaptive because it optimizes the timing and duration of behaviour. Current evidence indicates that ecological variables are the main determinants of sleep duration and intensity across species. C1 [Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat, Sch Med, Los Angeles, CA 90095 USA. [Siegel, Jerome M.] Vet Affairs Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat, Sch Med, Los Angeles, CA 90095 USA. EM JSiegel@ucla.edu FU Medical Research Service of the Veterans Affairs Greater Los Angeles Healthcare System [NS14610, HL41370, MH64109, NSF0234687] FX The author's work is supported by the Medical Research Service of the Veterans Affairs Greater Los Angeles Healthcare System, grants NS14610, HL41370, MH64109 and NSF0234687. I thank G. Barber and W. Domhoff for helpful comments. NR 121 TC 101 Z9 103 U1 5 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD OCT PY 2009 VL 10 IS 10 BP 747 EP 753 DI 10.1038/nrn2697 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 496MQ UT WOS:000269978800013 PM 19654581 ER PT J AU Saylor, PJ Smith, MR AF Saylor, Philip J. Smith, Matthew R. TI PROSTATE CANCER How can we improve the health of men who receive ADT? SO NATURE REVIEWS UROLOGY LA English DT Editorial Material ID ANDROGEN DEPRIVATION THERAPY; CARDIOVASCULAR-DISEASE; RISK AB Clinical research in recent years has produced a deepening appreciation of the metabolic consequences of androgen deprivation therapy. on the basis of this knowledge, proactive management of risk factors for diabetes and cardiovascular events is appropriate in men who receive this treatment for prostate cancer. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Claire & John Bertucci Ctr Genitourinary Canc, Dept Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Claire & John Bertucci Ctr Genitourinary Canc, Dept Oncol, 55 Fruit St,YAW 7, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [K24 CA121990, K24 CA121990-03] NR 10 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 J9 NAT REV UROL JI Nat. Rev. Urol. PD OCT PY 2009 VL 6 IS 10 BP 529 EP 531 DI 10.1038/nrurol.2009.195 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 503QO UT WOS:000270554400005 PM 19806171 ER PT J AU Quant, EC Norden, AD Drappatz, J Muzikansky, A Doherty, L LaFrankie, D Ciampa, A Kesari, S Wen, PY AF Quant, Eudocia C. Norden, Andrew D. Drappatz, Jan Muzikansky, Alona Doherty, Lisa LaFrankie, Debra Ciampa, Abigail Kesari, Santosh Wen, Patrick Y. TI Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab SO NEURO-ONCOLOGY LA English DT Article DE bevacizumab; high-grade glioma; malignant glioma ID PHASE-II TRIAL; GLIOBLASTOMA-MULTIFORME; 1ST RELAPSE; IRINOTECAN; THERAPY; VEGF; ANGIOGENESIS; TEMOZOLOMIDE; INHIBITION; INVASION AB Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that has efficacy in recurrent malignant gliomas, particularly in combination with irinotecan. However, responses are rarely durable. Continuation of bevacizumab in combination with another chemotherapeutic agent may demonstrate some activity. In this article we present a retrospective review of 54 patients with recurrent malignant gliomas who progressed on a bevacizumab containing regimen and were then treated with an alternate bevacizumab-containing regimen. All patients received intravenous bevacizumab (5-10 mg/kg) every 2 weeks alone or in combination with an additional chemotherapeutic agent, such as irinotecan. There was no limit on the number of prior therapies. Clinical characteristics and outcomes were reviewed. Tumor progression was determined by a combination of clinical status and radiographic changes. Patients were 33 men, 21 women (median age, 50 years; range, 23-72 years) with a median KPS score of 80 prior to the first bevacizumab containing regimen and 70 prior to the second regimen; median prior chemotherapy regimens including the first bevacizumab-containing regimen was 3 (range, 2-5). Median progression-free survival (PFS) on the first bevacizumab-containing regimen was 124 days (95% confidence interval [CI], 87-154 days); 6-month (6M)-PFS was 33%. Median PFS on the second bevacizumab-containing regimen was 37.5 days (95% CI, 34-42 days); 6M-PFS was 2%. Ten patients on the first regimen and 12 patients on the second regimen suffered grade 3/4 toxicities. Those patients with malignant gliomas who progressed despite a bevacizumab-containing regimen rarely responded to the second bevacizumab-containing chemotherapeutic regimen. In such patients, alternate therapies should be considered. Neuro-Oncology 11, 550-555, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00204, March 30, 2009. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2009-006) C1 [Quant, Eudocia C.; Norden, Andrew D.; Drappatz, Jan; Kesari, Santosh; Wen, Patrick Y.] Harvard Univ, Sch Med, Div Canc Neurol, Dept Neurol, Boston, MA USA. [Quant, Eudocia C.; Norden, Andrew D.; Drappatz, Jan; Doherty, Lisa; LaFrankie, Debra; Ciampa, Abigail; Kesari, Santosh; Wen, Patrick Y.] Harvard Univ, Sch Med, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Quant, Eudocia C.; Norden, Andrew D.; Drappatz, Jan; Kesari, Santosh; Wen, Patrick Y.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Hosp, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, SW430,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org RI Kesari, Santosh/E-8461-2013 NR 20 TC 88 Z9 89 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2009 VL 11 IS 5 BP 550 EP 555 DI 10.1215/15228517-2009-006 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 502XT UT WOS:000270494800009 PM 19332770 ER PT J AU Suntsova, N Kumar, S Guzman-Marin, R Alam, MN Szymusiak, R McGinty, D AF Suntsova, N. Kumar, S. Guzman-Marin, R. Alam, M. N. Szymusiak, R. McGinty, D. TI A role for the preoptic sleep-promoting system in absence epilepsy SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Absence epilepsy; Spike-wave discharges; Sleep; Median preoptic nucleus; Ventrolateral preoptic nucleus; GABAergic neurons; c-Fos; Neuronal activity; WAG/Rij rats ID IDIOPATHIC GENERALIZED EPILEPSY; WAKING DISCHARGE PATTERNS; SPIKE-WAVE DISCHARGES; C-FOS; GALANINERGIC NEURONS; SUBUNIT EXPRESSION; GABAERGIC NEURONS; GENETIC MODEL; WAG/RIJ RATS; SEIZURES AB Absence epilepsy (AE) in humans and the genetic AE model in WAG/Rij rats are both associated with abnormalities in sleep architecture that suggest insufficiency of the sleep-promoting mechanisms. In this study we compared the functionality of sleep-active neuronal groups within two well-established sleep-promoting sites, the ventrolateral and median preoptic nuclei (VLPO and MnPN, respectively), in WAG/Rij and control rats. Neuronal activity was assessed using c-Fos immunoreactivity and chronic single-unit recording techniques. We found that WAG/Rij rats exhibited a lack of sleep-associated c-Fos activation of GABAergic MnPN and VLPO neurons, a lower percentage of MnPN and VLPO cells increasing discharge during sleep and reduced firing rates of MnPN sleep-active neurons, compared to non-epileptic rats. The role of sleep-promoting mechanisms in pathogenesis of absence seizures was assessed in non-epileptic rats using electrical stimulation and chemical manipulations restricted to the MnPN. We found that fractional activation of the sleep-promoting system in waking was sufficient to elicit absence-like seizures. Given that reciprocally interrelated sleep-promoting and arousal neuronal groups control thalamocortical excitability, we hypothesize that malfunctioning of sleep-promoting system results in impaired ascending control over thalamocortical rhythmogenic mechanisms during wake-sleep transitions thus favoring aberrant thalamocortical oscillations. Our findings suggest a pathological basis for AE-associated sleep abnormalities and a mechanism underlying association of absence seizures with wake-sleep transitions. Published by Elsevier Inc. C1 [Suntsova, N.; Kumar, S.; Alam, M. N.; Szymusiak, R.; McGinty, D.] VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. [Suntsova, N.; Alam, M. N.; McGinty, D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Kumar, S.; Szymusiak, R.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Guzman-Marin, R.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Suntsova, N.] So Fed Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu 344091, Russia. [Kumar, S.] Univ Patna, Dept Zool, Patna 800005, Bihar, India. RP Suntsova, N (reprint author), VA Greater Los Angeles, Res Serv 151A3, Healthcare Syst, 16111 Plummer St, North Hills, CA 91343 USA. EM suntsova@ucla.edu; dmcginty@ucla.edu FU Medical Research Service of the Department of Veterans Affairs; NIH [MH075076, HL60296, NS-50939]; Sleep Research Society Foundation FX This research was supported by the Medical Research Service of the Department of Veterans Affairs, NIH grants MH075076, HL60296, NS-50939 and the J. Christian Gillin Research Grant from the Sleep Research Society Foundation (N.S.) We thank Dr. M.N. Shouse for helpful comments on the work and Keng-Tee Chew for technical assistance. References NR 62 TC 15 Z9 16 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2009 VL 36 IS 1 BP 126 EP 141 DI 10.1016/j.nbd.2009.07.005 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 536BJ UT WOS:000273016900013 PM 19631751 ER PT J AU Leslie-Mazwi, TM Avery, LL Sims, JR AF Leslie-Mazwi, T. M. Avery, Laura L. Sims, John R. TI Intra-arterial Air Thrombogenesis after Cerebral Air Embolism Complicating Lower Extremity Sclerotherapy SO NEUROCRITICAL CARE LA English DT Article DE Cerebral air embolism; Sclerotherapy; Hyperbaric oxygen ID VARICOSE-VEINS; FOAM SCLEROTHERAPY; GAS EMBOLISM; MICROEMBOLISM; MANAGEMENT; POSITION; BLOOD AB Cerebral arterial gas embolism is a potentially life-threatening event. Intraarterial air can occlude blood flow directly or cause thrombosis. Sclerotherapy is an extremely rare cause of cerebral arterial gas embolism. Case-report A 38-year-old female suffered acute onset of a left middle cerebral artery (LMCA) syndrome with an NIH stroke score of 11 approximately 10 min after lower extremity sclerotherapy. CT angiogram demonstrated LMCA intraarterial air. Patient fully recovered after hyperbaric oxygen treatment with complete resolution of intraarterial air. However, thrombus replaced intraarterial air despite anticoagulation with heparin. We provide radiological evidence of hyperbaric oxygen therapy resolving intraarterial air but also demonstrate the thrombogenic potential of this procedural complication. C1 [Sims, John R.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Leslie-Mazwi, T. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Dept Emergency Radiol, Boston, MA 02114 USA. RP Sims, JR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bldg 149 Rm 6403,13th St, Charlestown, MA 02129 USA. EM tleslie-mazwi@partners.org; lavery@partners.org; jsims@partners.org NR 19 TC 9 Z9 10 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD OCT PY 2009 VL 11 IS 2 BP 247 EP 250 DI 10.1007/s12028-009-9211-2 PG 4 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 495OG UT WOS:000269902300018 PM 19294535 ER PT J AU Greer, DM Strozyk, D Schwamm, LH AF Greer, David M. Strozyk, Dorothea Schwamm, Lee H. TI False Positive CT Angiography in Brain Death SO NEUROCRITICAL CARE LA English DT Article DE Brain death; CT angiography; Subarachnoid hemorrhage; Transcranial Doppler; SPECT ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; DIAGNOSIS AB Ancillary testing is frequently required in the determination of death by brain criteria, particularly in cases in which the clinical examination is drawn into question. Newer tests, such as computed tomographic angiography (CTA), have garnered enthusiasm for their ease of performance, but have not been validated as acceptable tests compared with a gold standard. We present a case of a 31-year-old patient who was felt to have cerebral circulatory arrest on CTA, but was subsequently found to have evidence of preserved cerebral blood flow on transcranial Doppler, thus precluding the diagnosis death by brain criteria. CTA is not a validated confirmatory test for cerebral circulatory arrest in brain death, and may be falsely positive. CTA should be studied further in comparison to validated tests, such as conventional angiography or single photon emission computed tomography (SPECT), before being accepted as a standard ancillary test in determining death by brain criteria. C1 [Greer, David M.; Strozyk, Dorothea; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, ACC 739A,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 7 TC 13 Z9 13 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD OCT PY 2009 VL 11 IS 2 BP 272 EP 275 DI 10.1007/s12028-009-9220-1 PG 4 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 495OG UT WOS:000269902300022 PM 19390993 ER PT J AU Busl, KM Greer, DM AF Busl, Katharina M. Greer, David M. TI Pitfalls in the Diagnosis of Brain Death SO NEUROCRITICAL CARE LA English DT Review DE Brain death; Coma; Diagnosis ID SOMATOSENSORY-EVOKED-POTENTIALS; TRANSCRANIAL DOPPLER ULTRASONOGRAPHY; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; UNUSUAL SPONTANEOUS MOVEMENTS; GUILLAIN-BARRE-SYNDROME; SEVERE HEAD-INJURY; STEM DEATH; APNEA TEST; BISPECTRAL INDEX; SPINAL REFLEXES AB Since the establishment of the concept of declaring death by brain criteria, a large extent of variability in the determination of brain death has been reported. There are no standardized practical guidelines, and major differences exist in the requirements for the declaration of brain death throughout the USA and internationally. The American Academy of Neurology published evidence-based practice parameters for the determination of brain death in adults in 1995, requiring the irreversible absence of clinical brain function with the cardinal features of coma, absent brainstem reflexes, and apnea, as well as the exclusion of reversible confounders. Ancillary tests are recommended in cases of uncertainty of the clinical diagnosis. Every step in the determination of brain death bears potential pitfalls which can lead to errors in the diagnosis of brain death. These pitfalls are presented here, and possible solutions identified. Suggestions are made for improvement in the standardization of the declaration of brain death. C1 [Busl, Katharina M.; Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 739A,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org NR 117 TC 23 Z9 23 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD OCT PY 2009 VL 11 IS 2 BP 276 EP 287 DI 10.1007/s12028-009-9231-y PG 12 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 495OG UT WOS:000269902300023 PM 19444652 ER PT J AU Muehlschlegel, S Selb, J Patel, M Diamond, SG Franceschini, MA Sorensen, AG Boas, DA Schwamm, LH AF Muehlschlegel, Susanne Selb, J. Patel, M. Diamond, S. G. Franceschini, M. A. Sorensen, A. G. Boas, D. A. Schwamm, L. H. TI Feasibility of NIRS in the Neurointensive Care Unit: A Pilot Study in Stroke Using Physiological Oscillations SO NEUROCRITICAL CARE LA English DT Article DE Near-infrared spectroscopy; Cerebrovascular disease; Stroke; Critical care ID NEAR-INFRARED SPECTROSCOPY; DYNAMIC CEREBRAL AUTOREGULATION; ARTERIAL-BLOOD PRESSURE; HUMAN BRAIN; DOMAIN ANALYSIS; FLOW VELOCITY; HEMODYNAMICS; SURGERY; STIMULATION; OXYGENATION AB Near-infrared spectroscopy (NIRS) is a non-invasive, real-time bedside modality sensitive to changes in cerebral perfusion and oxygenation and is highly sensitive to physiological oscillations at different frequencies. However, the clinical feasibility of NIRS remains limited, partly due to concerns regarding NIRS signal quantification, which relies on mostly arbitrary assumptions on hemoglobin concentrations and tissue layers. In this pilot study comparing stroke patients to healthy controls, we explored the utility of the interhemispheric correlation coefficient (IHCC) during physiological oscillations in detecting asymmetry in hemispheric microvascular hemodynamics. Using bi-hemispheric continuous-wave NIRS, 12 patients with hemispheric strokes and 9 controls were measured prospectively. NIRS signal was band-pass filtered to isolate cardiac (0.7-3 Hz) and respiratory (0.15-0.7 Hz) oscillations. IHCCs were calculated in both oscillation frequency bands. Using Fisher's Z-transform for non-Gaussian distributions, the IHCC during cardiac and respiratory oscillations were compared between both groups. Nine patients and nine controls had data of sufficient quality to be included in the analysis. The IHCCs during cardiac and respiratory oscillations were significantly different between patients versus controls (cardiac 0.79 +/- A 0.18 vs. 0.94 +/- A 0.07, P = 0.025; respiratory 0.24 +/- A 0.28 vs. 0.59 +/- A 0.3; P = 0.016). Computing the IHCC during physiological cardiac and respiratory oscillations may be a new NIRS analysis technique to quantify asymmetric microvascular hemodynamics in stroke patients in the neurocritical care unit. It allows each subject to serve as their own control obviating the need for arbitrary assumptions on absolute hemoglobin concentration. Future clinical applications may include rapid identification of patients with ischemic brain injury in the pre-hospital setting. This promising new analysis technique warrants further validation. C1 [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Neurol, Neurocrit Care Serv,UMASS Mem Med Ctr, Worcester, MA 01655 USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Anesthesia Crit Care & Surg, UMASS Mem Med Ctr, Worcester, MA 01655 USA. [Selb, J.; Patel, M.; Franceschini, M. A.; Sorensen, A. G.; Boas, D. A.] Harvard Univ, Athinoula Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA USA. [Diamond, S. G.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Sorensen, A. G.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schwamm, L. H.] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Muehlschlegel, S (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Neurocrit Care Serv,UMASS Mem Med Ctr, 55 Lake Ave N,Univ Campus S-5, Worcester, MA 01655 USA. EM susanne.muehlschlegel@umassmemorial.org OI Schwamm, Lee/0000-0003-0592-9145; Diamond, Solomon/0000-0002-7589-2942 FU National Institute of Health/National Center [P41RR14075] FX This work was supported by the National Institute of Health/National Center for Research Resources (P41RR14075; PI: David Boas). NR 30 TC 18 Z9 18 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD OCT PY 2009 VL 11 IS 2 BP 288 EP 295 DI 10.1007/s12028-009-9254-4 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 495OG UT WOS:000269902300024 PM 19649749 ER PT J AU Mata, IF Hutter, CM Gonzalez-Fernandez, MC de Pancorbo, MM Lezcano, E Huerta, C Blazquez, M Ribacoba, R Guisasola, LM Salvador, C Gomez-Esteban, JC Zarranz, JJ Infante, J Jankovic, J Deng, H Edwards, KL Alvarez, V Zabetian, CP AF Mata, Ignacio F. Hutter, Carolyn M. Gonzalez-Fernandez, Maria C. de Pancorbo, Marian M. Lezcano, Elena Huerta, Cecilia Blazquez, Marta Ribacoba, Renee Guisasola, Luis M. Salvador, Carlos Gomez-Esteban, Juan C. Zarranz, Juan J. Infante, Jon Jankovic, Joseph Deng, Hao Edwards, Karen L. Alvarez, Victoria Zabetian, Cyrus P. TI Lrrk2 R1441G-related Parkinson's disease: evidence of a common founding event in the seventh century in Northern Spain SO NEUROGENETICS LA English DT Article DE Parkinson disease; LRRK2; R1441G; Founder effect; Basques ID CLINICAL-FEATURES; SPANISH PATIENTS; GENETIC-ANALYSIS; G2019S MUTATION; ASHKENAZI JEWS; BASQUES; DIVERSITY; LINKAGE; IDENTIFICATION; FREQUENCY AB Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene together represent the most common genetic determinant of Parkinson's disease (PD) identified to date. The vast majority of patients with LRRK2-related PD reported in the literature carry one of three pathogenic substitutions: G2019S, R1441C, or R1441G. While G2019S and R1441C are geographically widespread, R1441G is most prevalent in the Basque Country and is rare outside of Northern Spain. We sought to better understand the processes that have shaped the current distribution of R1441G. We performed a haplotype analysis of 29 unrelated PD patients heterozygous for R1441G and 85 wild-type controls using 20 markers that spanned 15.1 Mb across the LRRK2 region. Nine of the patients were of Basque origin and 20 were non-Basques. We inferred haplotypes using a Bayesian approach and utilized a maximum-likelihood method to estimate the age of the most recent common ancestor. Significant but incomplete allele sharing was observed over a distance of 6.0 Mb and a single, rare ten-marker haplotype 5.8 Mb in length was seen in all mutation carriers. We estimate that the most recent common ancestor lived 1,350 (95% CI, 1,020-1,740) years ago in approximately the seventh century. We hypothesize that R1441G originated in the Basque population and that dispersion of the mutation then occurred through short-range gene flow that was largely limited to nearby regions in Spain. C1 [Mata, Ignacio F.; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, Seattle, WA 98108 USA. [Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Hutter, Carolyn M.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Gonzalez-Fernandez, Maria C.; de Pancorbo, Marian M.] Univ Basque Country, Serv Gen Invest Genom Banco ADN, Vitoria, Spain. [Lezcano, Elena; Gomez-Esteban, Juan C.; Zarranz, Juan J.] Hosp Cruces, Unidad Trastornos Movimiento, Baracaldo, Spain. [Huerta, Cecilia; Alvarez, Victoria] Hosp Univ Cent Asturias, Genet Mol Inst Invest Nefrol, Oviedo, Spain. [Blazquez, Marta; Guisasola, Luis M.; Salvador, Carlos] Hosp Univ Cent Asturias, Serv Neurol, Oviedo, Spain. [Ribacoba, Renee] Hosp Alvarez Buylla, Serv Neurol, Mieres, Spain. [Infante, Jon] Univ Cantabria, Serv Neurol, Hosp Univ Marques de Valdecilla, E-39005 Santander, Spain. [Jankovic, Joseph; Deng, Hao] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Deng, Hao] Cent S Univ, Ctr Med Expt, Xiangya Hosp 3, Changsha, Hunan, Peoples R China. RP Zabetian, CP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Zarranz, Juan Jose/E-2955-2012; Gomez, Juan Carlos/E-3020-2012; SGIKER, Cienciometria/A-5759-2012; OI Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian, Cyrus/0000-0002-7739-4306; MARTINEZ DE PANCORBO, MARIA DE LOS ANGELES/0000-0002-7408-6068 FU Basque Government and University of the Basque Country [S-PE07UN44]; NIH [NINDS, K08 NS044138]; Department of Veterans Affairs; Parkinson's Disease Foundation; Spanish Fondo de Investigacion Sanitaria [FIS PI070014, 05/008]; Veterans Integrated Service Network 20 Geriatric, Mental Illness, and Parkinson's Disease Research, Education, and Clinical Centers FX We dedicate this paper to our dear colleague, Dr. Luis M. Guisasola, a superb clinician, researcher, and educator, who recently passed away. We thank the individuals who participated in the study. This work was supported by the Basque Government and University of the Basque Country (grant S-PE07UN44, M. M. P. and M. C. G-F.); the NIH (NINDS, K08 NS044138, C. P. Z.); the Department of Veterans Affairs (Merit Review Award, C. P. Z.); the Parkinson's Disease Foundation (Fellowship Award, I. F. M.); the Spanish Fondo de Investigacion Sanitaria (grant FIS PI070014, J. I; grant 05/008, V. A.); and the Veterans Integrated Service Network 20 Geriatric, Mental Illness, and Parkinson's Disease Research, Education, and Clinical Centers. NR 44 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD OCT PY 2009 VL 10 IS 4 BP 347 EP 353 DI 10.1007/s10048-009-0187-z PG 7 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 501MM UT WOS:000270386000010 PM 19308469 ER PT J AU Bar-Shira, A Hutter, CM Giladi, N Zabetian, CP Orr-Urtreger, A AF Bar-Shira, Anat Hutter, Carolyn M. Giladi, Nir Zabetian, Cyrus P. Orr-Urtreger, Avi TI Ashkenazi Parkinson's disease patients with the LRRK2 G2019S mutation share a common founder dating from the second to fifth centuries SO NEUROGENETICS LA English DT Article DE Parkinson's disease; Haplotype; Ashkenazi Jews; LRRK2 G2019S mutation; Founder mutation ID 185DELAG BRCA1 MUTATION; FAMILIES; JEWS; IDENTIFICATION; PENETRANCE; PREVALENCE; PORTUGAL; EUROPE; AGE AB The LRRK2 G2019S mutation is a major genetic determinant of Parkinson's disease (PD) across the world that occurs at an elevated frequency in Ashkenazi Jews. We determined the LRRK2 haplotypes in 77 G2019S carriers, mostly Ashkenazi Jews, and in 50 noncarrier Ashkenazi PD patients, using 16 genetic markers. A single haplotype was detected in all mutation carriers, indicating that these individuals share a common founder. Using a maximum-likelihood method, we estimate that Ashkenazi Jews with G2019S share a common ancestor who lived similar to 1,830 (95% CI 1,560-2,160) years ago, around the second century, after the second Jewish Diaspora. C1 [Bar-Shira, Anat; Orr-Urtreger, Avi] Tel Aviv Sourasky Med Ctr, Genet Inst, IL-64239 Tel Aviv, Israel. [Giladi, Nir] Tel Aviv Sourasky Med Ctr, Movement Disorders Unit, Parkinson Ctr, Dept Neurol, IL-64239 Tel Aviv, Israel. [Giladi, Nir; Orr-Urtreger, Avi] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Hutter, Carolyn M.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Zabetian, Cyrus P.] Univ Washington, Sch Med, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Sch Med, Seattle, WA USA. RP Orr-Urtreger, A (reprint author), Tel Aviv Sourasky Med Ctr, Genet Inst, 6 Weizmann St, IL-64239 Tel Aviv, Israel. EM aviorr@tasmc.health.gov.il OI Zabetian, Cyrus/0000-0002-7739-4306 FU National Parkinson Foundation, Miami, USA; Tel Aviv Sourasky Medical Center Grant of Excellence; Wolfson and Kahn Foundations FX The assistance of Dr. Helena Yagev-More is gratefully acknowledged. This work was supported by grants from National Parkinson Foundation, Miami, USA, Tel Aviv Sourasky Medical Center Grant of Excellence, and Wolfson and Kahn Foundations. NR 29 TC 16 Z9 16 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD OCT PY 2009 VL 10 IS 4 BP 355 EP 358 DI 10.1007/s10048-009-0186-0 PG 4 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 501MM UT WOS:000270386000011 PM 19283415 ER PT J AU Westlye, LT Walhovd, KB Dale, AM Espeseth, T Reinvang, I Raz, N Agartz, I Greve, DN Fischl, B Fjell, AM AF Westlye, Lars T. Walhovd, Kristine B. Dale, Anders M. Espeseth, Thomas Reinvang, Ivar Raz, Naftali Agartz, Ingrid Greve, Douglas N. Fischl, Bruce Fjell, Anders M. TI Increased sensitivity to effects of normal aging and Alzheimer's disease on cortical thickness by adjustment for local variability in gray/white contrast: A multi-sample MRI study SO NEUROIMAGE LA English DT Article ID MILD COGNITIVE IMPAIRMENT; AGE-RELATED-CHANGES; HUMAN CEREBRAL-CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BRAIN-TISSUE SEGMENTATION; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; MEDIAL TEMPORAL-LOBE; DEMENTIA RATING CDR; WHITE-MATTER AB MRI-based estimates of cerebral morphometric properties, e.g. cortical thickness, are pivotal to studies of normal and pathological brain changes. These measures are based on automated or manual segmentation procedures, which utilize the tissue contrast between gray and white matter on T(1)-weighted MR images. Tissue contrast is unlikely to remain a constant property across groups of different age and health. An important question is therefore how the sensitivity of cortical thickness estimates is influenced by variability in WM/GM contrast. The effect of adjusting for variability in WM/GM contrast oil age sensitivity of cortical thickness was tested in 1189 healthy subjects from six different samples, enabling evaluation of consistency of effects within and between sites and scanners. Further, the influence of Alzheimer's disease (AD) diagnosis on cortical thickness with and Without correction for contrast was tested in an additional sample of 96 patients. In healthy controls, regional increases in the sensitivity of the cortical thickness measure to age were found after correcting for contrast. Across samples, the strongest effects were observed in frontal, lateral temporal and parietal areas. Controlling for contrast variability also increased the cortical thickness estimates' sensitivity to AD, thus replicating the finding in an independent clinical sample. The results showed increased sensitivity of cortical estimates to AD in areas earlier reported to be compromised in AD, including medial temporal, inferior and superior parietal regions. In sum, the findings indicate that adjusting for contrast can increase the sensitivity of MR morphometry to variables of interest. (C) 2009 Elsevier Inc. All rights reserved. C1 [Westlye, Lars T.; Walhovd, Kristine B.; Espeseth, Thomas; Reinvang, Ivar; Fjell, Anders M.] Univ Oslo, Dept Psychol, Ctr Study Human Cognit, N-0317 Oslo, Norway. [Walhovd, Kristine B.; Fjell, Anders M.] Ullevual Univ Hosp, Dept Neuropsychol, N-0407 Oslo, Norway. [Dale, Anders M.] Univ Calif San Diego, Multimodal Imaging Lab, San Diego, CA 92103 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Raz, Naftali] Wayne State Univ, Dept Psychol, Detroit, MI 48201 USA. [Raz, Naftali] Wayne State Univ, Inst Gerontol, Detroit, MI 48201 USA. [Agartz, Ingrid] Diakonhjemmet Hosp, Dept Psychiat Res, N-0319 Oslo, Norway. [Agartz, Ingrid] Univ Oslo, Dept Psychiat, N-0319 Oslo, Norway. [Agartz, Ingrid] Karolinska Hosp & Inst, HUBIN, Dept Clin Neurosci, Psychiat Sect, SE-17176 Stockholm, Sweden. [Greve, Douglas N.; Fischl, Bruce] Harvard Univ, Sch Med, Athinoula A Martinos Ctr, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02129 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Westlye, LT (reprint author), Univ Oslo, Dept Psychol, Ctr Study Human Cognit, N-0317 Oslo, Norway. EM l.t.westlye@psykologi.uio.no RI Dale, Anders/A-5180-2010; OI Agartz, Ingrid/0000-0002-9839-5391; Westlye, Lars T./0000-0001-8644-956X FU The Norwegian Research Council [177404/W50, 175066/D15, 154313/V50, 177458/V50]; National Institutes of Health [R01-NS39581, R37-AG11230, R01-RR13609, U54 EB005149]; Mental Illness and Neuroscience Discovery Institute; The Wallenberg Foundation; Swedish Medical Research Council [K2004-21X-15078-01A 45, K2007-62X-15077-04-1, K2007-62X-15078-04-3]; The National Center for Research Resources [P41-RR14075, R01 RR16594-01A1]; NCRR BIRN Morphometric Testbed [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550, R01 EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; National Alliance for Medical Image Computing (NAMIC); National Institutes of Health; Ellison Medical Foundation FX The Norwegian Research Council (177404/W50) to K.B.W., (175066/D15) to A.M.F., (154313/V50) to I.R., (177458/V50) to T.E.; University of Oslo to K.B.W. and A.M.F.: the National Institutes of Health (R01-NS39581, R37-AG11230, and R01-RR13609); the Mental Illness and Neuroscience Discovery Institute; The Wallenberg Foundation and the Swedish Medical Research Council (K2004-21X-15078-01A 45, K2007-62X-15077-04-1, and K2007-62X-15078-04-3). The National Center for Research Resources (P41-RR14075, R01 RR16594-01A1 and the NCRR BIRN Morphometric Testbed BIRN002, U24 RR021382); the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550, R01 EB006758); the National Institute for Neurological Disorders and Stroke (R01 NS052585-01); as well as the Mental Illness and Neuroscience Discovery Institute; and is part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NiH Roadmap for Medical Research (grant U54 EB005149); additional Support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation. We thank the developers of the OASIS (Open Access Series of Imaging Studies) database for access to MRI data constituting sample 5 and the AD and control group of the present NR 96 TC 41 Z9 41 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2009 VL 47 IS 4 BP 1545 EP 1557 DI 10.1016/j.neuroimage.2009.05.084 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 484HN UT WOS:000269035100044 PM 19501655 ER PT J AU Pichon, S de Gelder, B Grezes, J AF Pichon, Swann de Gelder, Beatrice Grezes, Julie TI Two different faces of threat. Comparing the neural systems for recognizing fear and anger in dynamic body expressions SO NEUROIMAGE LA English DT Article DE Emotion; Amygdala; Body language; Action; fMRI ID EVENT-RELATED FMRI; FACIAL EXPRESSIONS; PREFRONTAL CORTEX; BIOLOGICAL MOTION; HUMAN AMYGDALA; EMOTION RECOGNITION; MACAQUE MONKEYS; BRAIN RESPONSES; CEREBRAL-CORTEX; FUSIFORM GYRUS AB Being exposed to fear or anger signals makes us feel threatened and prompts us to prepare an adaptive response. Yet, while fear and anger behaviors are both threat signals, what counts as an adaptive response is often quite different. In contrast with fear, anger is often displayed with the aim of altering the behavior of the agent to which it is addressed. To identify brain responses that are common or specific to the perception of these two types of threat signals, we used functional magnetic resonance imaging and asked subjects to recognize dynamic actions expressing fear, anger and neutral behaviors. As compared with neutral actions, the perception of fear and anger behaviors elicited comparable activity increases in the left amygdala and temporal cortices as well as in the ventrolateral and the dorsomedial prefrontal cortex. Whereas the perception of fear elicited specific activity in the right temporoparietal junction, the perception of anger triggered condition-specific activity in a wider set of regions comprising the anterior temporal lobe, the premotor cortex and the ventromedial prefrontal cortex, consistent with the hypothesis that coping with threat from exposure to anger requires additional contextual information and behavioral adjustments. (C) 2009 Elsevier Inc. All rights reserved. C1 [Pichon, Swann; Grezes, Julie] Ecole Normale Super, Dept Etud Cognit, Cognit Neurosci Lab, INSERM,UMR 960, F-75005 Paris, France. [de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, Tilburg, Netherlands. [de Gelder, Beatrice] Harvard Univ, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA. RP Grezes, J (reprint author), Ecole Normale Super, Dept Etud Cognit, Cognit Neurosci Lab, INSERM,UMR 960, F-75005 Paris, France. EM julie.grezes@ens.fr RI pichon, swann/M-2966-2014; Grezes, Julie/E-5060-2016 OI pichon, swann/0000-0001-5697-702X; FU Human Frontier Science Program [HFSP-RGP0054/2004-C]; European Union Research Funding FP6 NEST program [FP6-2005-NEST-Path Imp 043403] FX We are grateful to Charlotte Sinke for subject recruiting and assistance in scanning participants, Lydia Pouga for help in collecting behavioral data, Sven Gijsen and France Maloumian for skilful technical assistance. This work was supported by the Human Frontier Science Program [HFSP-RGP0054/2004-C] and the European Union Research Funding FP6 NEST program [FP6-2005-NEST-Path Imp 043403]. NR 100 TC 72 Z9 75 U1 5 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2009 VL 47 IS 4 BP 1873 EP 1883 DI 10.1016/j.neuroimage.2009.03.084 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 484HN UT WOS:000269035100075 PM 19371787 ER PT J AU Badgaiyan, RD Fischman, AJ Alpert, NM AF Badgaiyan, Rajendra D. Fischman, Alan J. Alpert, Nathaniel M. TI Dopamine release during human emotional processing SO NEUROIMAGE LA English DT Article ID MEDIAL PREFRONTAL CORTEX; LONG-TERM-MEMORY; POTENTIATED STARTLE; RECEPTOR ANTAGONIST; AMYGDALA; RATS; VOLUNTEERS; ACTIVATION; SYSTEMS; SCHIZOPHRENIA AB Involvement of dopamine neurotransmission in human emotional processing is unclear but animal studies have indicated that it is critical for processing of fear response. In this experiment we examined dopaminergic involvement in the processing of human emotions. We used a novel dynamic molecular imaging technique to detect and map dopamine released during presentation of emotional stimuli. The technique exploited the competition between endogenously released dopamine and its ligand for receptor occupancy and involved dynamic voxel-wise measurement of the rate at which a dopamine receptor ligand ((18)F-Fallypride) was displaced from receptor sites during emotional processing. An increase in the rate indicated dopamine release. We found that the rate of ligand displacement increased significantly in the left amygdala, left medial temporal lobe (MTL) and left inferior frontal gyrus. The results provide the first direct evidence of dopaminergic modulation of human emotional processing and suggest that the modulation occurs at multiple levels of processing. This finding indicates that the neurocognitive models of human emotion should take into account dopaminergic effects, and that, there is a need to investigate whether manipulation of the dopaminergic system could be an alternate strategy for treatment of conditions in which emotional processing is impaired. (C) 2009 Elsevier Inc. All rights reserved. C1 [Badgaiyan, Rajendra D.; Alpert, Nathaniel M.] Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. [Badgaiyan, Rajendra D.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA 02114 USA. RP Badgaiyan, RD (reprint author), Massachusetts Gen Hosp, Div Nucl Med, White 427,55 Fruit St, Boston, MA 02114 USA. EM rajendra@wjh.harvard.edu FU NIH [1 R21MH073624, 1 R21MH079435]; Dana Foundation; Shriners Hospital for Children FX Grant support: NIH (1 R21MH073624 and 1 R21MH079435), Dana Foundation, and Shriners Hospital for Children. NR 33 TC 30 Z9 31 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2009 VL 47 IS 4 BP 2041 EP 2045 DI 10.1016/j.neuroimage.2009.06.008 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 484HN UT WOS:000269035100092 PM 19524047 ER PT J AU Damaraju, E Huang, YM Barrett, LF Pessoa, L AF Damaraju, Eswar Huang, Yang-Ming Barrett, Lisa Feldman Pessoa, Luiz TI Affective learning enhances activity and functional connectivity in early visual cortex SO NEUROPSYCHOLOGIA LA English DT Article DE Primary visual cortex; Conditioning; Faces; Vision; Emotion; fMRI ID EVENT-RELATED FMRI; EMOTIONAL FACES; PREFRONTAL CORTEX; BINOCULAR-RIVALRY; MACAQUE MONKEY; AMYGDALA; ACTIVATION; PERCEPTION; ATTENTION; STIMULI AB This study examined the impact of task-irrelevant affective information on early visual processing regions V1-V4. Fearful and neutral faces presented with rings of different colors were used as stimuli. During the conditioning phase, fearful faces presented with a certain ring color (e.g., black) were paired with mild electrical stimulation. Neutral faces shown with rings of that color, as well as fearful or neutral faces shown with another ring color (e.g., white), were never paired with shock. Our findings revealed that fearful faces evoked enhanced blood oxygen level dependent (BOLD) responses in V1 and V4 compared to neutral faces. Faces embedded in a color ring that was paired with shock (e.g., black) evoked greater BOLD responses in V1-V4 compared to a ring color that was never paired with shock (e.g., white). Finally, BOLD responses in early visual cortex were tightly interrelated (i.e., correlated) during an affectively potent context (i.e., ring color) but not during a neutral one, suggesting that increased functional integration was present with affective learning. Taken together, the results suggest that task-irrelevant affective information not only influences evoked responses in early, retinotopically organized visual cortex, but also determines the pattern of responses across early visual cortex. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Damaraju, Eswar; Huang, Yang-Ming; Pessoa, Luiz] Indiana Univ, Bloomington, IN 47405 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Boston Coll, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Huang, YM (reprint author), Indiana Univ, 1101 E 10th St, Bloomington, IN 47405 USA. EM yangming.huang@gmail.com OI Huang, Yang-Ming/0000-0001-5791-6325 FU National Institutes of Health Director's Pioneer Award [DP1OD003312]; National Institute of Aging [AG030311]; National Science Foundation [BCS 0721260, BCS 0527440]; Army Research Institute [W91WAW]; American Philosophical Society to Lisa Feldman Barrett; National Institute of Mental Health [MH071589] FX Preparation of this manuscript was supported by a National Institutes of Health Director's Pioneer Award (DP1OD003312), grants from the National Institute of Aging (AG030311) and the National Science Foundation (BCS 0721260, BCS 0527440), and a contract with the Army Research Institute (W91WAW), as well as by a James McKeen Cattell Award and a Sabbatical Fellowship from the American Philosophical Society to Lisa Feldman Barrett. Support was also provided by a grant from the National Institute of Mental Health (MH071589) to Luiz Pessoa. The authors thank the anonymous reviewers for their constructive feedback. NR 50 TC 25 Z9 26 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD OCT PY 2009 VL 47 IS 12 BP 2480 EP 2487 DI 10.1016/j.neuropsychologia.2009.04.023 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 482DJ UT WOS:000268864000015 PM 19410587 ER PT J AU Lo, AC Guarino, P Krebs, HI Volpe, BT Bever, CT Duncan, PW Ringer, RJ Wagner, TH Richards, LG Bravata, DM Haselkorn, JK Wittenberg, GF Federman, DG Corn, BH Maffucci, AD Peduzzi, P AF Lo, Albert C. Guarino, Peter Krebs, Hermano I. Volpe, Bruce T. Bever, Christopher T. Duncan, Pamela W. Ringer, Robert J. Wagner, Todd H. Richards, Lorie G. Bravata, Dawn M. Haselkorn, Jodie K. Wittenberg, George F. Federman, Daniel G. Corn, Barbara H. Maffucci, Alysia D. Peduzzi, Peter TI Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE Stroke; Rehabilitation; Robotics; Randomized clinical trial; Health economics ID HEALTH UTILITIES INDEX; CLINICAL-TRIALS; RECOVERY; THERAPY; ARM; INFORMATION; IMPACT; NEUROREHABILITATION; STIMULATION; PERFORMANCE AB Background. Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective. To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods. The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment >= 6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results. A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. Conclusions. VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010. C1 [Lo, Albert C.] Brown Univ, Providence VA Med Ctr, VA RR&D Ctr Excellence, Ctr Restorat & Regenerat Med, Providence, RI 02909 USA. [Guarino, Peter; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter] VA Connecticut Healthcare Syst, Coordinating Ctr, VA Cooperat Studies Program, West Haven, CT USA. [Krebs, Hermano I.] MIT, Cambridge, MA 02139 USA. [Volpe, Bruce T.] Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY USA. [Bever, Christopher T.] Univ Maryland, Sch Med, VA Maryland Healthcare Syst, Baltimore, MD 21201 USA. [Bever, Christopher T.; Wittenberg, George F.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Duncan, Pamela W.] Duke Univ, Duke Ctr Clin Hlth Policy Res, Durham, NC USA. [Ringer, Robert J.] Clin Res Pharm Coordinating Ctr, VA Cooperat Studies Program, Albuquerque, NM USA. [Wagner, Todd H.] VA Palo Alto Healthcare Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Richards, Lorie G.] N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [Richards, Lorie G.] Univ Florida, Gainesville, FL USA. [Bravata, Dawn M.] Richard L Roudebush VAMC, Indianapolis, IN USA. [Haselkorn, Jodie K.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Haselkorn, Jodie K.] Univ Washington, Seattle, WA 98195 USA. [Wittenberg, George F.] Univ Maryland, Sch Med, Vet Affairs Med Ctr Baltimore Geriatr Res, Educ & Clin Ctr, Baltimore, MD 21201 USA. [Federman, Daniel G.] Yale Univ, New Haven, CT USA. RP Lo, AC (reprint author), Brown Univ, Providence VA Med Ctr, VA RR&D Ctr Excellence, Ctr Restorat & Regenerat Med, 830 Chalkstone Ave,111N, Providence, RI 02909 USA. EM Albert.Lo@va.gov OI Volpe, Bruce/0000-0002-1098-1848 FU Department of Veterans Affairs Cooperative Studies Program; Department of Veterans Affairs Rehabilitation Research and Development Service FX VA ROBOTICS was supported by the Department of Veterans Affairs Cooperative Studies Program and the Department of Veterans Affairs Rehabilitation Research and Development Service. Dr H. I. Krebs is a coinventor in the MIT-held patent for the robotic device used in this study. He holds equity positions in Interactive Motion Technologies, Inc, the company that manufactures this type of technology under license to MIT. NR 51 TC 35 Z9 36 U1 0 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD OCT PY 2009 VL 23 IS 8 BP 775 EP 783 DI 10.1177/1545968309338195 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 494YV UT WOS:000269856900001 PM 19541917 ER PT J AU Strozyk, D Nogueira, RG Lavine, SD AF Strozyk, Dorothea Nogueira, Raul G. Lavine, Sean D. TI Endovascular Treatment of Intracranial Arteriovenous Malformation SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Review DE Arteriovenous malformation; Endovascular treatment; Intracranial hemorrhage; Embolization; NBCA; Onyx ID N-BUTYL CYANOACRYLATE; HEREDITARY HEMORRHAGIC TELANGIECTASIA; PREEMBOLIZATION FUNCTIONAL-EVALUATION; CEREBRAL VASCULAR MALFORMATIONS; POLYVINYL-ALCOHOL PARTICLES; CENTRAL-NERVOUS-SYSTEM; TERM-FOLLOW-UP; NATURAL-HISTORY; PREOPERATIVE EMBOLIZATION; STEREOTACTIC RADIOSURGERY AB Arteriovenous malformations (AVMs) of the brain are vascular lesions in which an abnormal tangle or nidus of vessels permits pathologic shunting of blood flow from the arterial to the venous tree without an intervening capillary bed. With brain imaging techniques, an increasing number of AVMs are detected before they hemorrhage, leading to new considerations and modifications of interdisciplinary management strategies. Treatment options include endovascular embolization, microsurgical resection, radiosurgery, medical management, or a combination of these. Neuroendovascular therapy is a critical component of this multidisciplinary and multimodal approach. The development and introduction of newer techniques and agents will continue to affect embolization treatments. C1 [Lavine, Sean D.] Columbia Univ, Med Ctr, Neurol Inst,Dept Neurosurg, Coll Phys & Surg, New York, NY 10032 USA. [Strozyk, Dorothea; Lavine, Sean D.] Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. [Nogueira, Raul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Lavine, SD (reprint author), Columbia Univ, Med Ctr, Neurol Inst,Dept Neurosurg, Coll Phys & Surg, 710 W 168th St,4th Floor 424, New York, NY 10032 USA. EM S12081@columbia.edu NR 132 TC 9 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD OCT PY 2009 VL 20 IS 4 BP 399 EP + DI 10.1016/j.nec.2009.07.004 PG 21 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 520TI UT WOS:000271871100003 PM 19853800 ER PT J AU Keyhani, S Federman, A AF Keyhani, Salomeh Federman, Alex TI Doctors on Coverage -- Physicians' Views on a New Public Insurance Option and Medicare Expansion. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Keyhani, Salomeh] James J Peters Vet Adm Med Ctr, Bronx, NY USA. [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA. [Keyhani, Salomeh; Federman, Alex] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. RP Keyhani, S (reprint author), James J Peters Vet Adm Med Ctr, Bronx, NY USA. NR 3 TC 16 Z9 16 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 1 PY 2009 VL 361 IS 14 DI 10.1056/NEJMp0908239 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 500KZ UT WOS:000270300000005 PM 19752465 ER PT J AU Cook, J Jakupcak, M Rosenheck, R Fontana, A McFall, M AF Cook, Jessica Jakupcak, Matthew Rosenheck, Robert Fontana, Alan McFall, Miles TI Influence of PTSD symptom clusters on smoking status among help-seeking Iraq and Afghanistan veterans SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; SCRIPT-DRIVEN IMAGERY; MAJOR DEPRESSION; COMBAT VETERANS; NEGATIVE AFFECT; TWIN REGISTRY; WAR VETERANS; PRIMARY-CARE; NICOTINE AB Despite the strong association between smoking and posttraumatic stress disorder (PTSD), mechanisms influencing smoking in this population remain unclear. Previous smoking research has largely examined PTSD as a homogenous syndrome despite the fact that PTSD is composed of four distinct symptom clusters (i.e., reexperiencing, effortful avoidance, emotional numbing, and hyperarousal). Examination of the relationship between smoking and PTSD symptom clusters may increase understanding of mechanisms influencing comorbidity between smoking and PTSD. The goals of the present study were to (a) examine the influence of overall PTSD symptom severity on likelihood of smoking and smoking heaviness and (b) examine the influence of each PTSD symptom cluster on smoking. Participants (N = 439) were Operation Iraqi Freedom/Operation Enduring Freedom combat veterans referred to VA mental health services. Multinomial logistic regression was chosen to accommodate a three-level outcome, in which the likelihood of being a nonsmoker was compared with (a) light smoking (1-9 cigarettes/day), (b) moderate smoking (10-19 cigarettes/day), and (c) heavy smoking (>= 20 cigarettes/day). Results showed that veterans with higher levels of overall PTSD symptomatology were more likely to endorse heavy smoking (Wald = 4.56, p = .03, odds ratio [OR] = 1.65). Veterans endorsing high levels of emotional numbing were also more likely to endorse heavy smoking (Wald = 6.49, p = .01, OR = 1.81); all other PTSD symptom clusters were unrelated to smoking. The association between emotional numbing and heavy daily smoking suggests that veterans with PTSD may smoke to overcome emotional blunting following trauma exposure. C1 [Cook, Jessica] Univ Wisconsin, Ctr Tobacco Res & Intervent, Sch Med & Publ Hlth, Madison, WI 53711 USA. [Jakupcak, Matthew; McFall, Miles] Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst, Sch Med, Seattle, WA 98195 USA. [Rosenheck, Robert; Fontana, Alan] Yale Univ, Sch Med, NE Evaluat Program, VA Natl Ctr PTSD,Evaluat Ctr, New Haven, CT USA. RP Cook, J (reprint author), Univ Wisconsin, Ctr Tobacco Res & Intervent, Sch Med & Publ Hlth, 1930 Monroe St,Suite 200, Madison, WI 53711 USA. EM jwcook@ctri.medicine.wisc.edu FU VA Puget Sound Health Care System, Seattle, WA [K08DA021311] FX This work is supported by K08DA021311 to Dr. Cook. This material is supported by resources from the VA Puget Sound Health Care System, Seattle, WA. NR 41 TC 23 Z9 23 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD OCT PY 2009 VL 11 IS 10 BP 1189 EP 1195 DI 10.1093/ntr/ntp123 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 496VX UT WOS:000270008900009 PM 19648174 ER PT J AU Stylopoulos, N Hoppin, AG Kaplan, LM AF Stylopoulos, Nicholas Hoppin, Alison G. Kaplan, Lee M. TI Roux-en-Y Gastric Bypass Enhances Energy Expenditure and Extends Lifespan in Diet-induced Obese Rats SO OBESITY LA English DT Article ID LONG-TERM MORTALITY; HEALTH-CARE USE; WEIGHT-LOSS; BODY-WEIGHT; BARIATRIC SURGERY; FOOD-INTAKE; ILEAL TRANSPOSITION; GLUCOSE-METABOLISM; PLASMA GHRELIN; MORBID-OBESITY AB Gastrointestinal weight-loss surgery (GIWLS) is currently the most effective treatment for severe obesity, with Roux-en-Y gastric bypass (RYGB) among the best of the available surgical options. Despite its widespread clinical use, the mechanisms by which RYGB induces its profound weight loss remain largely unknown. This procedure effects weight loss by altering the physiology of weight regulation and eating behavior rather than by simple mechanical restriction and/or malabsorption as previously thought. To study how RYGB affects the physiology of energy balance, we developed a rat model of this procedure. In this report, we demonstrate that RYGB in diet-induced obese (DIO) rats induces a 25% weight loss, prolongs mean survival by 45%, and normalizes glucose homeostasis and lipid metabolism. RYGB induced a 19% increase in total and a 31% increase in resting energy expenditure (REE). These effects, along with a 17% decrease in food intake and a 4% decrease in nutrient absorption account for the normalization of body weight after this procedure. These effects indicate that surgery acts by altering the physiology of weight regulation and help to explain the effectiveness of RYGB in comparison to restrictive dieting and other forms of dietary and pharmacological therapies for obesity. The clinical effectiveness of RYGB and its physiological effects on body weight regulation and energy expenditure (EE) suggest that this operation provides a unique opportunity to explore the mechanisms of energy homeostasis and to identify novel therapies for obesity and related metabolic diseases. C1 [Stylopoulos, Nicholas; Hoppin, Alison G.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Stylopoulos, Nicholas; Hoppin, Alison G.; Kaplan, Lee M.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Stylopoulos, Nicholas; Hoppin, Alison G.; Kaplan, Lee M.] Harvard Univ, Sch Med, Boston, MA USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM lmkaplan@partners.org FU NIH [DK057478, DK046200, DK043351, DK002671, HD052961] FX We thank David Rattner and Jeffrey Pettit for their contributions to the early development of the rat RYGB model, Dennis Chen for help with statistical analyses, and Philip Davis for technical assistance. these studies were supported by NIH grants DK057478, DK046200, DK043351 (L. M. K.), and DK002671 (A. G. H.) and training award HD052961 (N. S.). NR 50 TC 115 Z9 115 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2009 VL 17 IS 10 BP 1839 EP 1847 DI 10.1038/oby.2009.207 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 502UD UT WOS:000270484800005 PM 19556976 ER PT J AU Pe'er, J Hochberg, FH Foster, CS AF Pe'er, Jacob Hochberg, Fred. H. Foster, C. Stephen TI Clinical Review:Treatment of Vitreoretinal Lymphoma SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Review DE Vitreoretinal lymphoma; primary central nervous system lymphoma (PCNSL); chemotherapy; radiation therapy; biological therapy ID CENTRAL-NERVOUS-SYSTEM; PRIMARY INTRAOCULAR LYMPHOMA; RETICULUM-CELL SARCOMA; PRIMARY CNS LYMPHOMA; COLLABORATIVE GROUP-REPORT; BRAIN-BARRIER DISRUPTION; INTRAVITREAL METHOTREXATE; RITUXIMAB INJECTIONS; RADIATION-THERAPY; OCULAR LYMPHOMA AB Vitreoretinal lymphoma is the most common type of intraocular lymphoma. It is mostly a high-grade B-cell malignancy with a poor prognosis, and is often associated with primary central nervous system lymphoma. Since intraocular lymphoma was first recognized almost 60 years ago, its treatment has gradually evolved. In the early years enucleation was often performed. Since that time, radiation therapy alone, systemic chemotherapy alone, or a combination of the two have been used extensively Because of the limited intraocular penetration of drugs administered systemically, the systemic and local toxicity of chemotherapy and radiation therapy and the high rate of recurrence, intravitreous chemotherapy, mainly using methotrexate, has become popular in the last decade, with encouraging results. More recently, biological treatment with intravitreal injections of rituximab has been investigated, with good results and minimal side effects. This review summarizes the present knowledge on vitreoretinal lymphoma therapy, with an eye to future molecular approaches. C1 [Pe'er, Jacob] Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, IL-91120 Jerusalem, Israel. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Eye Res & Surg Inst, Boston, MA USA. RP Pe'er, J (reprint author), Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, POB 12000, IL-91120 Jerusalem, Israel. EM peer@hadassah.org.il NR 59 TC 22 Z9 22 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD OCT PY 2009 VL 17 IS 5 BP 299 EP 306 DI 10.3109/09273940903370755 PG 8 WC Ophthalmology SC Ophthalmology GA 520HF UT WOS:000271832700001 PM 19831557 ER PT J AU Sharifi, E Porco, TC Naseri, A AF Sharifi, Emile Porco, Travis C. Naseri, Ayman TI Cost-Effectiveness Analysis of Intracameral Cefuroxime Use for Prophylaxis of Endophthalmitis after Cataract Surgery SO OPHTHALMOLOGY LA English DT Article ID ANTERIOR SEGMENT SYNDROME; VIGAMOX(R) MOXIFLOXACIN 0.5-PERCENT; PENICILLIN-ALLERGIC PATIENTS; OCULAR SURFACE FLUID; OCCULT-BLOOD TESTS; POSTOPERATIVE ENDOPHTHALMITIS; PREVENTING ENDOPHTHALMITIS; INCISION TYPE; RABBIT MODEL; RISK-FACTORS AB Objective: To evaluate the cost-effectiveness of intracameral cefuroxime for postoperative endophthalmitis prophylaxis, and to determine the efficacy threshold necessary for alternative antibiotics to attain cost-effective equivalence with intracameral cefuroxime. Design: Cost-effectiveness analysis. Participants: We study a hypothetical cohort of 100 000 patients undergoing cataract surgery as a part of the cost analysis. Methods: A cost-effectiveness model was constructed to analyze different antibiotic prophylactic regimens for postoperative endophthalmitis with intracameral cefuroxime as our base case. Efficacy was defined as the absolute reduction in rate of infection from background rate of infection, which was sourced from the literature. Antibiotic cost data were derived from the Red Book 2007 edition, and salary data were taken from the United States Bureau of Labor Statistics. Multivariate sensitivity analysis assessed the performance of antibiotic options under different scenarios. Main Outcome Measures: Cost per case of endophthalmitis prevented; theoretical maximal cost-effectiveness; efficacy threshold necessary to achieve cost-effective equivalence with intracameral cefuroxime; ratio indicating how many times more effective or less expensive alternative antibiotics would have to be to achieve cost-effective equivalence with intracameral cefuroxime. Results: The cost-effectiveness ratio for intracameral cefuroxime is $1403 per case of postoperative endophthalmitis prevented. By comparison, the least expensive topical fluoroquinolone in our study, ciprofloxacin, would have to be >8 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. The most expensive topical fluoroquinolones studied, gatifloxacin and moxifloxacin, would have to be >= 19 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. A sensitivity analysis reveals that even in the worst case scenario for intracameral cefuroxime efficacy and with a 50% reduction in the cost of 4th-generation fluoroquinolones, gatifloxacin and moxifloxacin would have to be >= 9 times more effective than intracameral cefuroxime to achieve cost-effective equivalence. Conclusions: Administration of intracameral cefuroxime is relatively cost-effective in preventing endophthalmitis after cataract surgery. Owing to their high costs, many commonly used topical antibiotics are not cost-effective compared with intracameral cefuroxime, even under optimistic assumptions about their efficacy. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2009;116:1887-1896 (C) 2009 by the American Academy of Ophthalmology. C1 [Sharifi, Emile; Porco, Travis C.; Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Naseri, Ayman] San Francisco Vet Adm Med Ctr, Dept Ophthalmol, San Francisco, CA 94121 USA. [Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Prevent Med & Publ Hlth, Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA 94143 USA. RP Naseri, A (reprint author), San Francisco Vet Adm Med Ctr, Dept Ophthalmol, 4150 Clement St, San Francisco, CA 94121 USA. EM ayman.naseri@va.gov FU That Man May See, San Francisco, CA; Research to Prevent Blindness, New York, NY; NIH [P30 EY002162] FX Supported in part by an unrestricted grant from That Man May See, San Francisco, CA, an unrestricted grant from Research to Prevent Blindness, New York, NY, and by a Core Grant For Vision Research (NIH P30 EY002162). NR 59 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2009 VL 116 IS 10 BP 1887 EP 1896 DI 10.1016/j.ophtha.2009.03.014 PG 10 WC Ophthalmology SC Ophthalmology GA 506RX UT WOS:000270794600009 PM 19560825 ER PT J AU Hekiert, AM Kofonow, JM Doghramji, L Kennedy, DW Chiu, AG Palmer, JN Leid, JG Cohen, NA AF Hekiert, Adrianna M. Kofonow, Jennifer M. Doghramji, Laurel Kennedy, David W. Chiu, Alexander G. Palmer, James N. Leid, Jeffery G. Cohen, Noam A. TI Biofilms correlate with T(H)1 inflammation in the sinonasal tissue of patients with chronic rhinosinusitis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID BACTERIAL BIOFILMS; CHRONIC SINUSITIS; PSEUDOMONAS-AERUGINOSA; STAPHYLOCOCCUS-AUREUS; NASAL POLYPOSIS; MODEL; INTERLEUKIN-5; PROFILES; HEALTH; CARE AB OBJECTIVE: Determine the prevalence of bacterial biofilms in surgical chronic rhinosinusitis (CRS) patients and characterize the inflammatory response associated with biofilm CRS. STUDY DESIGN: Cross-sectional. SETTING: Tertiary care academic center. SUBJECTS AND METHODS: Sinonasal mucosa and peripheral blood were collected from 60 CRS patients. Mucosal biofilms were demonstrated by scanning electron microscopy. Leukocyte subpopulations were determined by flow cytometry. Cytokines were identified with a luminex-based assay on the lysate of homogenized tissue or plasma. RESULTS: Of the 60 samples, 17 were determined to be positive for the presence of biofilms. Oral steroid-naive CRS patients with biofilm demonstrated a local T(H)1 inflammatory response with significantly elevated levels of interferon-gamma (INF-gamma), granulocyte colony-stimulating factor, macrophage inflammatory protein-1 beta, and neutrophils in the sinonasal mucosa. No differences were present at the systemic level. CONCLUSION: Sinonasal bacterial biofilms correlate to a T(H)1 skewed local but not systemic inflammatory response in CRS. This difference is abrogated by the use of oral steroids. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [Hekiert, Adrianna M.; Kofonow, Jennifer M.; Doghramji, Laurel; Kennedy, David W.; Chiu, Alexander G.; Palmer, James N.; Cohen, Noam A.] Univ Penn, Sch Med, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. [Kofonow, Jennifer M.; Cohen, Noam A.] Philadelphia VA Med Ctr, Dept Otorhinolaryngol, Philadelphia, PA USA. [Leid, Jeffery G.] No Arizona Univ, Ctr Microbial Genet & Genom, Flagstaff, AZ 86011 USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Div Rhinol, Ravdin Bldg,5th Flr, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu RI Chiu, Alexander/J-1230-2014; OI Chiu, Alexander/0000-0002-7592-6575; Cohen, Noam/0000-0002-9462-3932 FU American Academy of Otolaryngic Allergy; Sinus and Allergy Health Partnership FX This project was funded by a CORE resident grant from the American Academy of Otolaryngic Allergy to A.M.H. and a Young Investigator Award from the Sinus and Allergy Health Partnership to N.A.C. NR 22 TC 34 Z9 36 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2009 VL 141 IS 4 BP 448 EP 453 DI 10.1016/j.otohns.2009.06.090 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 502GK UT WOS:000270443800003 PM 19786211 ER PT J AU Borsook, D AF Borsook, David TI Ketamine and chronic pain - Going the distance SO PAIN LA English DT Editorial Material ID OPEN-LABEL; EFFICACY C1 [Borsook, David] Harvard Univ, PAIN Grp, Massachusetts Gen Hosp, Sch Med, Boston, MA 02478 USA. [Borsook, David] Harvard Univ, PAIN Grp, McLean Hosp, Sch Med, Boston, MA 02478 USA. [Borsook, David] Harvard Univ, PAIN Grp, Childrens Hosp, Sch Med, Boston, MA 02478 USA. RP Borsook, D (reprint author), Harvard Univ, PAIN Grp, Massachusetts Gen Hosp, Sch Med, Boston, MA 02478 USA. EM dborsook@partners.harvard.edu FU NINDS NIH HHS [K24 NS064050, K24 NS064050-02] NR 20 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 2009 VL 145 IS 3 BP 271 EP 272 DI 10.1016/j.pain.2009.05.021 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 502NR UT WOS:000270467700004 PM 19573988 ER PT J AU Haskell, SG Brandt, CA Krebs, EE Skanderson, M Kerns, RD Goulet, JL AF Haskell, Sally G. Brandt, Cynthia A. Krebs, Erin E. Skanderson, Melissa Kerns, Robert D. Goulet, Joseph L. TI Pain among Veterans of Operations Enduring Freedom and Iraqi Freedom: Do Women and Men Differ? SO PAIN MEDICINE LA English DT Article DE Pain Assessment; Veterans; Sex Differences ID POSTTRAUMATIC-STRESS-DISORDER; RECEIVING PRIMARY-CARE; PERSIAN-GULF-WAR; HEALTH-CARE; GENERAL-POPULATION; GENDER-DIFFERENCES; FEMALE VETERANS; UNITED-STATES; PREVALENCE; AGE AB Objective. To evaluate sex differences in the prevalence of overall pain, moderate-severe pain, and persistent pain among Veterans of Operations Enduring Freedom and Iraqi Freedom seen at VA outpatient clinics, and to evaluate sex differences in pain assessment. Design. The observational cohort consisted of Veterans discharged from the U.S. military from October 1, 2001 to November 30, 2007 that enrolled for Veterans Administration (VA) services or received VA care before January 1, 2008. We limited the sample to the 153,212 Veterans (18,481 female, 134,731 male) who had 1 year of observation after their last deployment. Results. Pain was assessed in 59.7% (n = 91,414) of Veterans in this sample. Among those assessed, 43.3% (n = 39,591) reported any pain, 63.2% (n = 25,028) of whom reported moderate-severe pain. Over 20% (n = 3,427) of Veterans with repeated pain measures reported persistent pain. We found no significant difference in the probability of pain assessment by sex (RR = 0.98, 95% CI 0.96, 1.00). Female Veterans were less likely to report any pain (RR 0.89, 95% CI 0.86, 0.92). Among those with any pain, female Veterans were more likely to report moderate-severe pain (RR 1.05, 95% CI 1.01, 1.09) and less likely to report persistent pain (RR 0.90, 95% CI 0.81, 0.99). Conclusions. As the VA plans care for the increasing numbers of female Veterans returning from Iraq and Afghanistan, a better understanding of the prevalence of pain, as well as sex-specific variations in the experience and treatment of pain, is important for policy makers and providers who seek to improve identification and management of diverse pain disorders. C1 [Haskell, Sally G.; Brandt, Cynthia A.; Kerns, Robert D.; Goulet, Joseph L.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Krebs, Erin E.] Roudebush VA Ctr Implementing Evidence Based Prac, Indianapolis, IN USA. [Krebs, Erin E.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Krebs, Erin E.] Regenstrief Inst Inc, Indianapolis, IN USA. [Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Haskell, Sally G.; Brandt, Cynthia A.; Kerns, Robert D.; Goulet, Joseph L.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Haskell, Sally G.; Brandt, Cynthia A.; Kerns, Robert D.; Goulet, Joseph L.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Haskell, Sally G.; Brandt, Cynthia A.; Kerns, Robert D.; Goulet, Joseph L.] Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06510 USA. RP Goulet, JL (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave, West Haven, CT 06516 USA. EM Joseph.Goulet@VA.gov OI Goulet, Joseph/0000-0002-0842-804X FU VA [DHI 07-065-1]; VA HSR&D Research Enhancement Award Program (REAP) PRIME Project [CD207215-2] FX Financial support: VA grants DHI 07-065-1 (Brandt PI, Haskell, Skanderson); VA HSR&D Research Enhancement Award Program (REAP) PRIME Project (Kerns PI; Goulet); CD207215-2 (Krebs PI). NR 48 TC 35 Z9 35 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2009 VL 10 IS 7 BP 1167 EP 1173 DI 10.1111/j.1526-4637.2009.00714.x PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 504BT UT WOS:000270589100003 PM 19818028 ER PT J AU Helfand, M Freeman, M AF Helfand, Mark Freeman, Michele TI Assessment and Management of Acute Pain in Adult Medical Inpatients: A Systematic Review SO PAIN MEDICINE LA English DT Article DE Pain Management; Hospital Medicine; Systematic Reviews ID PATIENT-CONTROLLED ANALGESIA; ACUTE ABDOMINAL-PAIN; EMERGENCY-DEPARTMENT; OLDER-ADULTS; COGNITIVE IMPAIRMENT; EPIDURAL ANALGESIA; ACUTE APPENDICITIS; OPIOID ANALGESIA; SELF-ASSESSMENT; EFFICACY AB Objective. To review the literature addressing effective care for acute pain in inpatients on medical wards. Methods. We searched Medline, PubMed Clinical Queries, and the Cochrane Database for systematic reviews published in 1996 through April 2007 on the assessment and management of acute pain in inpatients, including patients with impaired self-report or chemical dependencies. We conducted a focused search for studies on the timing and frequency of assessment, and on the use of patient-controlled analgesia (PCA) for nonsurgical pain. Two investigators performed a critical analysis of the literature and compiled narrative summaries to address the key questions. Results. We found no evidence that directly linked the timing, frequency, or method of pain assessment with outcomes or safety in medical inpatients. There is good evidence that treating abdominal pain does not compromise timely diagnosis and treatment of the surgical abdomen. Pain management teams and other systemwide interventions improve assessment and use of analgesics, but do not clearly affect pain outcomes. The safety and effectiveness of PCA in medical patients have not been studied. There is weak evidence that most cognitively impaired individuals can understand at least one self-assessment measure. Almost no evidence is available to guide management of pain in delirium. Evidence for managing pain in patients with substance abuse disorders or chronic opioid use is weak, being derived from case reports, retrospective studies, and expert opinion. Conclusions. Pain is a prevalent problem for medical inpatients. Clinical research is needed to guide the assessment and management of pain in this setting. C1 Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Evidence Based Synth Program, Portland, OR 97201 USA. Oregon Evidence Based Practice Ctr, Portland, OR USA. RP Helfand, M (reprint author), Portland VA Med Ctr, Mailcode RD71,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM mark.helfand@va.gov FU Department of Veterans Affairs, VHA [01-0206] FX The research reported here was supported by the Department of Veterans Affairs, VHA Project ESP 05-225, VA #01-0206. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. We gratefully acknowledge the assistance of research librarians Andrew Hamilton and Rose Campbell, and the participation of Robert D. Kerns, PhD, Jack Rosenberg, MD, Karl Lorenz, MD, and Roger Chou, MD, in helping us identify and refine key questions, and critically reviewing drafts of the findings. NR 92 TC 27 Z9 27 U1 1 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2009 VL 10 IS 7 BP 1183 EP 1199 DI 10.1111/j.1526-4637.2009.00718.x PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 504BT UT WOS:000270589100005 PM 19818030 ER PT J AU Dobscha, SK Clark, ME Morasco, BJ Freeman, M Campbell, R Helfand, M AF Dobscha, Steven K. Clark, Michael E. Morasco, Benjamin J. Freeman, Michele Campbell, Rose Helfand, Mark TI Systematic Review of the Literature on Pain in Patients with Polytrauma Including Traumatic Brain Injury SO PAIN MEDICINE LA English DT Article DE Pain; Multiple Trauma; Blast Injuries; Traumatic Brain Injury; Veterans ID PERIPHERAL-NERVE LESIONS; LONG-TERM OUTCOMES; INTRATHECAL BACLOFEN THERAPY; HEAD-INJURY; MULTIPLE TRAUMA; MAJOR TRAUMA; FOLLOW-UP; FUNCTIONAL CONSEQUENCES; SPASTIC HYPERTONIA; RISK-FACTORS AB Objective. To review the literature addressing the assessment and management of pain in patients with polytraumatic injuries including traumatic brain injury (TBI) and blast-related headache, and to identify patient, clinician and systems factors associated with pain-related outcomes. Design. Systematic review. Methods. We conducted searches in MEDLINE of literature published from 1950 through July 2008. Due to a limited number of studies using controls or comparators, we included observational and rigorous qualitative studies. We systematically rated the quality of systematic reviews, cohort, and case-control design studies. Results. One systematic review, 93 observational studies, and one qualitative research study met inclusion criteria. The literature search yielded no published studies that assessed measures of pain intensity or pain-related functional interference among patients with cognitive deficits due to TBI, that compared patients with blast-related headache with patients with other types of headache, or that assessed treatments for blast-related headache pain. Studies on the association between TBI severity and pain reported mixed findings. There was limited evidence that the following factors are associated with pain among TBI patients: severity, location, and multiplicity of injuries; insomnia; fatigue; depression; and post-traumatic stress disorder. Conclusions. Very little evidence is currently available to guide pain assessment and treatment approaches in patients with polytrauma. Further research employing systematic observational as well as controlled intervention designs is clearly indicated. C1 [Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Portland, OR 97207 USA. [Dobscha, Steven K.; Morasco, Benjamin J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Dobscha, Steven K.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97207 USA. [Clark, Michael E.] James A Haley Vet Affairs Hosp, Psychol Serv, Tampa, FL USA. [Clark, Michael E.] Univ S Florida, Coll Med, Dept Psychol, Jacksonville, FL USA. [Clark, Michael E.] Univ S Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Freeman, Michele; Campbell, Rose] Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Box 1034 P3MHADM, Portland, OR 97207 USA. EM steven.dobscha@va.gov FU Department of Veterans Affairs; Veterans Health Administration, Health Services Research and Development Service [RCD 04129]; National Institutes of Health [K23DA023467-01A1]; Agency for Healthcare Research and Quality FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Project RCD 04129 (Dobscha), National Institutes of Health K23DA023467-01A1 (Morasco) and Evidence-based Practice Center funding which is supported by the Agency for Healthcare Research and Quality. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 90 TC 46 Z9 47 U1 1 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2009 VL 10 IS 7 BP 1200 EP 1217 DI 10.1111/j.1526-4637.2009.00721.x PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 504BT UT WOS:000270589100006 PM 19818031 ER PT J AU Lorenz, KA Krebs, EE Bentley, TGK Sherbourne, CD Goebel, JR Zubkoff, L Lanto, AB Asch, SM AF Lorenz, Karl A. Krebs, Erin E. Bentley, Tanya G. K. Sherbourne, Cathy D. Goebel, Joy R. Zubkoff, Lisa Lanto, Andy B. Asch, Steven M. TI Exploring Alternative Approaches to Routine Outpatient Pain Screening SO PAIN MEDICINE LA English DT Article DE Ambulatory Care; Veterans; Pain; Measurement ID 5TH VITAL SIGN; PRIMARY-CARE; IMPACT; VALIDITY; INFORMATION; IMPAIRMENT; INVENTORY; QUALITY AB Objective. To evaluate potential alternatives to the numeric rating scale (NRS) for routine pain screening. Design. Cross-sectional. Setting. Nineteen Veterans Affairs outpatient clinics in Southern California at two hospitals and six community sites. Patients. Five hundred twenty-eight veterans from primary care, cardiology, and oncology clinics sampled in proportion to the total number of visits made to each clinic during the previous year. Methods. Veterans were approached following clinic visits to complete researcher-administered surveys about their clinic experience. Using the Brief Pain Inventory (BPI) interference scale of >= 5 as a reference standard for important unrelieved pain, we evaluated potential alternative pain screening items and item combinations by analyzing sensitivity and specificity, area under the receiver operating curve (AUC), and likelihood ratios. Results. Of the veterans, 43.6% had unrelieved pain as measured by the reference standard. Approximately half had painful musculoskeletal diagnoses and one-third had comorbid mental health or substance use disorders. The fifth vital sign detected pain less accurately than did an NRS with a 1-week timeframe and an item assessing pain-related bother over the past week. AUCs were 0.79, 0.86, and 0.86, respectively. A sequential approach combining the pain-related bother and NRS with a 1-week timeframe items had good discriminatory ability. Conclusions. Alternative single or combined pain screening strategies assessing pain-related bother may improve routine pain detection. C1 [Lorenz, Karl A.; Zubkoff, Lisa; Lanto, Andy B.; Asch, Steven M.] Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. [Lorenz, Karl A.; Bentley, Tanya G. K.; Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lorenz, Karl A.; Sherbourne, Cathy D.; Asch, Steven M.] Univ Calif Los Angeles, Ctr Hlth Policy Res, Los Angeles, CA USA. [Krebs, Erin E.] Richard L Roudebush Vet Adm Med Ctr, Ctr Implementing Evidence Based Practice, Indianapolis, IN 46202 USA. [Krebs, Erin E.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Krebs, Erin E.] Regenstrief Inst Inc, Indianapolis, IN USA. [Goebel, Joy R.] Calif State Univ Long Beach, Dept Nursing, Long Beach, CA 90840 USA. RP Lorenz, KA (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM Karl.lorenz@med.va.gov FU VA Health Services Research and Development (HSRD) Service [IIR 03-150] FX This study was supported by a grant from the VA Health Services Research and Development (HSRD) Service (IIR 03-150). Dr. Erin Krebs is supported by a VA HSRD Career Development Award. NR 35 TC 8 Z9 8 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2009 VL 10 IS 7 BP 1291 EP 1299 DI 10.1111/j.1526-4637.2009.00709.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 504BT UT WOS:000270589100014 PM 19818039 ER PT J AU Otis, JD Keane, TM Kerns, RD Monson, C Scioli, E AF Otis, John D. Keane, Terence M. Kerns, Robert D. Monson, Candice Scioli, Erica TI The Development of an Integrated Treatment for Veterans with Comorbid Chronic Pain and Posttraumatic Stress Disorder SO PAIN MEDICINE LA English DT Article DE Pain; Iraq; Veterans; Military Personnel; Posttraumatic Stress Disorder; Wounds and Injuries ID COGNITIVE PROCESSING THERAPY; LOW-BACK-PAIN; OPERATIONS ENDURING FREEDOM; RANDOMIZED CONTROLLED TRIAL; MUTUAL MAINTENANCE; BEHAVIOR-THERAPY; IRAQI FREEDOM; DISTRESS; HEALTH; CARE AB Objective. The purpose of this article is to describe the development of the first integrated treatment for Veterans with comorbid chronic pain and posttraumatic stress disorder (PTSD). Design. Descriptive, including pre- and posttreatment assessment results from a pilot study of six veterans with comorbid chronic pain and PTSD. Setting. Northeastern Department of Veterans Affairs Medical Center. Interventions. Using components of cognitive processing therapy (CPT) for PTSD and cognitive behavioral therapy (CBT) for chronic pain management, a 12-session integrated treatment for veterans with comorbid chronic pain and PTSD was developed. A therapist manual and patient workbook that included weekly readings and homework assignments were created. Participants received pre- and posttreatment evaluations using measures of pain, PTSD, physical disability, and psychological distress. The treatment development process is reviewed and the benefits and challenges of implementing this integrated treatment are presented. Results. Several themes emerged over the course of implementing the treatment, including the importance of establishing participant trust, regular therapy attendance, and addressing participant avoidance. Of the six participants recruited for the pilot study, three withdrew from the study and three completed the integrated treatment. Participants reported that they generally liked the format of treatment, appreciated learning about the ways that chronic pain and PTSD share some common symptoms, and ways that the two disorders can interact with one another. The assessment results of those who completed treatment suggest that this treatment approach is feasible and may have clinical benefit. Conclusions. Participants appeared to benefit from receiving the integrated treatment for pain and PTSD. A randomized clinical trial is currently being conducted to evaluate the efficacy of this treatment approach. C1 [Otis, John D.; Keane, Terence M.; Monson, Candice; Scioli, Erica] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Otis, John D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Otis, John D.; Keane, Terence M.; Monson, Candice] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Kerns, Robert D.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Kerns, Robert D.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Kerns, Robert D.] Yale Univ, Dept Neurol & Psychiat, New Haven, CT USA. RP Otis, JD (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM John.otis@va.gov OI Otis, John/0000-0002-5441-7421 FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation, Research and Development Service (RR&D), VA Merit Review [C3322R]; Research Service of the VA Boston Healthcare System FX This work was supported by a Department of Veterans Affairs, Veterans Health Administration, Rehabilitation, Research and Development Service (RR&D), VA Merit Review Grant (C3322R) and by the Research Service of the VA Boston Healthcare System. The authors would like to acknowledge the participation of Alex MacDonald PhD, Jay Morrison MA, and Mary Murawski PhD. NR 44 TC 47 Z9 47 U1 0 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2009 VL 10 IS 7 BP 1300 EP 1311 DI 10.1111/j.1526-4637.2009.00715.x PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 504BT UT WOS:000270589100015 PM 19818040 ER PT J AU Crowley-Matoka, M Saha, S Dobscha, SK Burgess, DJ AF Crowley-Matoka, Megan Saha, Somnath Dobscha, Steven K. Burgess, Diana J. TI Problems of Quality and Equity in Pain Management: Exploring the Role of Biomedical Culture SO PAIN MEDICINE LA English DT Review DE Pain Management; Disparities; Biomedical Culture ID CHRONIC NONCANCER PAIN; CLINICAL-PRACTICE GUIDELINE; PRIMARY-CARE PHYSICIANS; OPIOID ANALGESICS; CANCER PAIN; ETHNIC DISPARITIES; POSTOPERATIVE PAIN; AMERICAN ACADEMY; PATIENT; MEDICINE AB Objectives. To explore how social scientific analyses of the culture of biomedicine may contribute to advancing our understanding of ongoing issues of quality and equity in pain management. Design. Drawing upon the rich body of social scientific literature on the culture of biomedicine, we identify key features of biomedical culture with particular salience for pain management. We then examine how these cultural features of biomedicine may shape key phases of the pain management process in ways that have implications not just for quality, but for equity in pain management as well. Setting and Patients. We bring together a range of literatures in developing our analysis, including literatures on the culture of biomedicine, pain management and health care disparities. Measures. We surveyed the relevant literatures to identify and inter-relate key features of biomedical culture, key phases of the pain management process, and key dimensions of identified problems with suboptimal and inequitable treatment of pain. Results. We identified three key features of biomedical culture with critical implications for pain management: 1) mind-body dualism; 2) a focus on disease vs illness; and 3) a bias toward cure vs care. Each of these cultural features play a role in the key phases of pain management, specifically pain-related communication, assessment and treatment decision-making, in ways that may hinder successful treatment of pain in general-and of pain patients from disadvantaged groups in particular. Conclusions. Deepening our understanding of the role of biomedical culture in pain management has implications for education, policy and research as part of ongoing efforts to ameliorate problems in both quality and equity in managing pain. In particular, we suggest that building upon the existing the cultural competence movement in medicine to include fostering a deeper understanding of biomedical culture and its impact on physicians may be useful. From a policy perspective, we identify pain management as an area where the need for a shift to a more biopsychosocial model of health care is particularly pressing, and suggest prioritization of inter-disciplinary, multimodal approaches to pain as one key strategy in realizing this shift. Finally, in terms of research, we identify the need for empirical research to assess aspects of biomedical culture that may influence physician's attitudes and behaviors related to pain management, as well as to explore how these cultural values and their effects may vary across different settings within the practice of medicine. C1 [Crowley-Matoka, Megan] Univ Pittsburgh, Pittsburgh, PA USA. [Crowley-Matoka, Megan] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Saha, Somnath; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, Somnath; Dobscha, Steven K.] Portland VA Med Ctr, Portland, OR USA. [Burgess, Diana J.] Univ Minnesota, Minneapolis, MN USA. [Burgess, Diana J.] Minneapolis Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. RP Crowley-Matoka, M (reprint author), VA Pittsburgh Healthcare Syst 646, CHERP, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM Megan.Matoka@med.va.gov RI Burgess, Diana/A-1946-2016 FU VA HSRD Merit Review [VA IIR 05-210-01] FX The authors have no relevant financial relationships to declare. Dr. Crowley-Matoka's work on this manuscript was supported by a VA HSR&D Merit Review award (VA IIR 05-210-01). NR 116 TC 29 Z9 30 U1 1 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD OCT PY 2009 VL 10 IS 7 BP 1312 EP 1324 DI 10.1111/j.1526-4637.2009.00716.x PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 504BT UT WOS:000270589100016 PM 19818041 ER PT J AU Reeve, JR Liddle, RA AF Reeve, Joseph R., Jr. Liddle, Rodger A. TI A Tribute to Gary M. Green (1940-2008) IN MEMORIAM SO PANCREAS LA English DT Biographical-Item C1 [Reeve, Joseph R., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Liddle, Rodger A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Reeve, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Bldg 115 Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jreeve@ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD OCT PY 2009 VL 38 IS 7 BP 719 EP 720 DI 10.1097/MPA.0b013e3181b13795 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 500BL UT WOS:000270271900001 ER PT J AU Sahani, DV Holalkere, NS Kambadakone, A Matthes, K Mino-Kenudson, M Brugge, WR AF Sahani, Dushyant V. Holalkere, Nagaraj-Setty Kambadakone, Avinash Matthes, Kai Mino-Kenudson, Mari Brugge, William R. TI Role of Computed Tomography Perfusion in the Evaluation of Pancreatic Necrosis and Pancreatitis After Endoscopic Ultrasound-Guided Ablation of the Pancreas in a Porcine Model SO PANCREAS LA English DT Article DE CT perfusion; pancreatic necrosis; pancreatitis; ethanol ablation; porcine ID TUMOR ANGIOGENESIS; PROGNOSTIC VALUE; BLOOD-FLOW; CONTRAST ENHANCEMENT; DYNAMIC CT; HELICAL CT; PARAMETERS; ISCHEMIA; CANCER; STROKE AB Objectives: To evaluate the role of computed tomography (CT) perfusion in detection of pancreatic necrosis and pancreatitis after endoscopic ultrasound-guided ethanol ablation of porcine pancreas and to correlate the evaluation with histopathology. Methods: Under endoscopic ultrasound guidance, 0.9% saline (control) and ethanol at 60%, 80%, and 100% concentrations were injected into the pancreatic tails of 4 pigs. On day 4, dynamic perfusion CT of the pancreas was performed. Perfusion analysis and evaluation of enhancement characteristics were done and correlated with histopathology. Results: Ethanol injections at 80% and 100% concentrations resulted in focal necrosis surrounded by focal pancreatitis, whereas 60% ethanol injection caused severe focal pancreatitis with microscopic necrosis. The necrotic area revealed reduced blood flow, blood volume, permeability-surface area product, and increased mean transit time compared with pancreatitis and normal tissue (P <= 0.001). In the control pig, no pancreatitis or necrosis was observed on perfusion images and histopathology. Conclusions: Pancreatic necrosis and pancreatitis after ethanol injection reduced the tissue perfusion on CT in comparison to normal tissue, with the changes being more substantial in necrosis than pancreatitis. These findings have possible implications in the accurate detection of pancreatic necrosis in patients with severe pancreatitis. C1 [Sahani, Dushyant V.; Holalkere, Nagaraj-Setty; Kambadakone, Avinash] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Matthes, Kai] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Gastroenterol, Boston, MA 02215 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 45 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD OCT PY 2009 VL 38 IS 7 BP 775 EP 781 DI 10.1097/MPA.0b013e3181a66fa6 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 500BL UT WOS:000270271900010 PM 19465884 ER PT J AU Parchman, ML Flannagan, D Ferrer, RL Matamoras, M AF Parchman, Michael L. Flannagan, Dorothy Ferrer, Robert L. Matamoras, Mike TI Communication competence, self-care behaviors and glucose control in patients with type 2 diabetes SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Diabetes mellitus, Type 2; Communication; Blood glucose; Physician-patient relations ID PARTICIPATORY DECISION-MAKING; PHYSICIAN COMMUNICATION; HEALTH-CARE; DISPARITIES; MANAGEMENT; OUTCOMES; QUALITY; MODEL AB Objective: To examine the relationship between physician communication competence and A1c control among Hispanics and non-Hispanics seen in primary care practices. Study design: Observational. Methods: Direct observation and audio-recording of patient-physician encounters by 155 Hispanic and non-Hispanic white patients seen by 40 physicians in 20 different primary care clinics. Audio-recordings were transcribed and coded to derive an overall communication competence score for the physician. An exit survey was administered to each patient to assess self-care activities and their medical record was abstracted for the most recent glycosylated hemoglobin (A1c) level. Results: Higher levels of communication competence were associated with lower levels of A1c for Hispanics, but not non-Hispanic white patients. Although communication competence was associated with better self-reported diet behaviors, diet was not associated with A1c control. Across all patients, higher levels of communication competence were associated with improved A1c control after controlling for age, ethnicity and diet adherence. Conclusions: Physician's communication competence may be more important for promoting clinical success in disadvantaged patients. Practice implications: Acquisition of communication competence skills may be an important component in interventions to eliminate Hispanic disparities in glucose control. Published by Elsevier Ireland Ltd. C1 [Parchman, Michael L.; Ferrer, Robert L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Flannagan, Dorothy; Matamoras, Mike] Univ Texas San Antonio, Dept Psychol, San Antonio, TX USA. RP Parchman, ML (reprint author), S Texas Vet Hlth Care Syst, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU Agency for Healthcare Research and Quality [K08 HS013008-02]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FX This research was supported by the Agency for Healthcare Research and Quality (Grant #K08 HS013008-02) and the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. We would like to express our appreciation to the physicians and offices staff in the South Texas Ambulatory Research Network (STARNet) for their participation in this study. NR 30 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2009 VL 77 IS 1 BP 55 EP 59 DI 10.1016/j.pec.2009.03.006 PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 500UW UT WOS:000270332000011 PM 19359125 ER PT J AU Okamatsu, C London, WB Naranjo, A Hogarty, MD Gastier-Foster, JM Look, AT LaQuaglia, M Maris, JM Cohn, SL Matthay, KK Seeger, RC Saji, T Shimada, H AF Okamatsu, Chizuko London, Wendy B. Naranjo, Arlene Hogarty, Michael D. Gastier-Foster, Julie M. Look, A. Thomas LaQuaglia, Michael Maris, John M. Cohn, Susan L. Matthay, Katherine K. Seeger, Robert C. Saji, Tsutomu Shimada, Hiroyuki TI Clinicopathological Characteristics of Ganglioneuroma and Ganglioneuroblastoma: A Report From the CCG and COG SO PEDIATRIC BLOOD & CANCER LA English DT Article DE clinical staging; ganglioneuroblastoma; ganglioneuroma; International Neuroblastoma Pathology Classification; prognosis; tumor resectability ID NEUROBLASTOMA PATHOLOGY CLASSIFICATION; PEDIATRIC-ONCOLOGY-GROUP; NEURO-BLASTOMA; PROGNOSTIC FACTORS; SCHWANNIAN STROMA; SHIMADA SYSTEM; TUMORS; DIAGNOSIS; FEATURES; CRITERIA AB Background. The International Neuroblastoma Pathology Classification INPC) was the first to clearly define prognostic subgroups in ganglioneuroma (GN) and ganglioneuroblastoma (GNB). Procedure. Histopathology and tumor resectability of 552 GN/GNB cases from the Children's Cancer Group (CCG) and Children's Oncology Group (COG) neuroblastoma studies were reviewed. The results were analyzed along with clinical information and biological data of the cases. Results. According to the INPC, 300 tumors were classified into the Favorable Histology (FH) group and 252 were into the Unfavorable Histology (UH) group. Tumors in the FH group included 43 ganglioneuroma-maturing (GN-M), 198 ganglioneuroblastoma-intermixed (GNB-I), and 59 ganglioneuroblastorna-nodular, favorable Subset (GNB-N-FS), and were often (91%) resected completely by single or multiple surgical procedures. Patients with the FH tumors had an excellent prognosis with no tumor-related deaths. The UH group included ganglioneuroblastoma-nodular, unfavorable Subset (GNB-N-US) tumors. Patients with the UH tumors had a high incidence (53%) of distant metastasis at the time of diagnosis, and their prognosis significantly depended oil clinical stage (5-year EFS: 80.1% for non-stage 4 patients; 16.7% for stage 4 patients): Complete primary tumor resection was not beneficial to those GNB-N-US patients, regardless of whether metastasis was present or not. MYCN amplification was detected in four tumors in the FH group and six tumors in the UH group. The majority (160/191, 849%) of GN-M and GNB-I tumors had a diploid pattern determined by flow cytometry. Conclusions. Stringent application of the INPC along with clinical staging was critical for prognostic evaluation of the patients with this group Of tumors. Pediatr Blood Cancer 2009;53:563-569. (C) 2009 Wiley-Liss, Inc. C1 [Okamatsu, Chizuko; Shimada, Hiroyuki] Univ So Calif, Dept Pathol & Lab Med, Childrens Hosp Los Angeles, Keck Sch Med, Los Angeles, CA 90027 USA. [Okamatsu, Chizuko; Saji, Tsutomu] Toho Univ, Omori Med Ctr, Dept Pediat, Tokyo, Japan. [London, Wendy B.; Naranjo, Arlene] Univ Florida, Dept Epidemiol & Hlth Policy Res, Childrens Oncol Grp, Gainesville, FL USA. [Hogarty, Michael D.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH USA. [Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pathol & Pediat, Columbus, OH 43210 USA. [Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [LaQuaglia, Michael] Mem Sloan Kettering Canc Ctr, Dept Pediat Surg, New York, NY 10021 USA. [Cohn, Susan L.] Univ Chicago, Dept Pediat, Div Hematol Oncol, Chicago, IL 60637 USA. [Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Seeger, Robert C.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90033 USA. RP Shimada, H (reprint author), Univ So Calif, Dept Pathol & Lab Med, Childrens Hosp Los Angeles, Keck Sch Med, MS 43,4650 Sunset Blvd, Los Angeles, CA 90027 USA. EM hshimada@chla.usc.edu RI Gastier-Foster, Julie/E-3105-2011; OI Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [U10 CA098413, U10 CA098413-02, U10 CA98413] NR 30 TC 18 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2009 VL 53 IS 4 BP 563 EP 569 DI 10.1002/pbc.22106 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 487SJ UT WOS:000269295500010 PM 19530234 ER PT J AU Mansbach, JM Clark, S Barcega, BRB Haddad, H Camargo, CA AF Mansbach, Jonathan M. Clark, Sunday Barcega, Besh R. B. Haddad, Haitham Camargo, Carlos A., Jr. TI Factors Associated With Longer Emergency Department Length of Stay for Children With Bronchiolitis A Prospective Multicenter Study SO PEDIATRIC EMERGENCY CARE LA English DT Article DE bronchiolitis; length of stay; quality of care ID PEDIATRIC HOSPITALIZATIONS; RESOURCE UTILIZATION; MANAGEMENT; CARE; INFANTS; RATES; ADMISSION; LANGUAGE; QUALITY; ILLNESS AB Objectives: Emergency department (ED) length of stay (LOS) is a quality of care measure and, when prolonged, contributes to ED crowding. Bronchiolitis, a common seasonal illness of infants, provides an opportunity to examine factors affecting ED LOS. Methods: We analyzed data from a 30-center prospective cohort study of ED patients younger than 2 years with an attending physician diagnosis of bronchiolitis to determine what factors affect LOS. Researchers conducted a structured interview and chart review. Results: Among 1459 children enrolled, ED LOS was available for 1416 children (97%). The median ED LOS was 3.3 hours (interquartile range, 2.3-4.8 hours). Multivariate analysis demonstrated that factors significantly (P < 0.05) associated with ED LOS were larger annual ED visit volume (reference, lowest tertile [<44,134 visits], 44,134-62,420 [b = 0.74], and >= 62,421 [beta = 0.63]), Hispanic race/ethnicity (reference, white race, beta = 1.43), lack of primary care provider (beta = 1.28), duration of symptoms of 4 to 7 days (reference, <1 day; beta = 0.58), presentation of midnight to 7 AM (reference, 4:00-11:59 PM; beta = 1.07), decreasing lowest oxygen saturation in ED (beta = 0.07), fewer number of beta-agonists during the first hour (beta = 0.74), unknown oral intake (reference, adequate; beta = 0.69), performance of chest x-ray (beta = 0.62), and hospital admission (beta = 1.11). Conclusions: In this prospective multicenter study of children younger than 2 years with bronchiolitis, multiple factors were associated with longer ED LOS. These factors suggest the following steps to help shorten ED LOS: optimizing translation services, improving primary care provider rates, enhancing overnight patient flow, forgoing chest x-rays, and developing evidence-based admission criteria. C1 [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Barcega, Besh R. B.] Loma Linda Univ, Med Ctr, Dept Emergency Med, Loma Linda, CA USA. [Haddad, Haitham] Rainbow Babies Childrens Hosp, Div Emergency Med, Cleveland, OH USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Main Clin Bldg 9 S,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 36 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD OCT PY 2009 VL 25 IS 10 BP 636 EP 641 PG 6 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 508VK UT WOS:000270965200004 PM 21465688 ER PT J AU Buijze, GA SnoepMd, AWH Brevoord, J AF Buijze, Geert Alexander SnoepMd, Anneke Willemina Hanna Brevoord, Judith TI SEROGROUP C MENINGOCOCCAL OSTEOMYELITIS A CASE REPORT AND REVIEW OF THE LITERATURE SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE osteomyelitis; meningococcus; children ID ACUTE HEMATOGENOUS OSTEOMYELITIS; SEPTIC ARTHRITIS AB A rare case of a 7-year-old boy with acute hematogenous osteomyelitis caused by Neisseria meningitidis serogroup C is presented. The diagnosis of osteomyelitis was made by bone scintigraphy and a blood culture confirmed meningococci as the cause of the disease. Meningococcal osteomyelitis is exceptionally rare and to our knowledge, serogroup C meningococci have not been previously reported as a cause. C1 [Buijze, Geert Alexander] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA 02114 USA. [SnoepMd, Anneke Willemina Hanna] Ekwendeni Mission Hosp, Dept Pediat, Ekwendeni, Malawi. [Brevoord, Judith] Dept Pediat, Zoetermeer, Neth Antilles. RP Buijze, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, 55 Fruit St,YAW 2, Boston, MA 02114 USA. EM gbuijze@partners.org NR 10 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 2009 VL 28 IS 10 BP 929 EP 930 DI 10.1097/INF.0b013e3181a81398 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 501UI UT WOS:000270407800020 PM 20135846 ER PT J AU Small, JE Gonzalez, GE Nagao, KE Walton, DS Caruso, PA AF Small, Juan E. Gonzalez, Guido E. Nagao, Karina E. Walton, David S. Caruso, Paul A. TI Optic neuropathy in a patient with pyruvate dehydrogenase deficiency SO PEDIATRIC RADIOLOGY LA English DT Article DE Pyruvate dehydrogenase deficiency; Optic neuropathy AB Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. C1 [Small, Juan E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Small, Juan E.; Gonzalez, Guido E.; Nagao, Karina E.; Walton, David S.; Caruso, Paul A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gonzalez, Guido E.; Caruso, Paul A.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Nagao, Karina E.; Walton, David S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Small, JE (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St GRB 290, Boston, MA 02114 USA. EM jsmall1@partners.org NR 3 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2009 VL 39 IS 10 BP 1114 EP 1117 DI 10.1007/s00247-009-1344-0 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 495AH UT WOS:000269861000017 PM 19588132 ER PT J AU Vinci, RJ Bauchner, H Finkelstein, J Newby, PK Muret-Wagstaff, S Lovejoy, FH AF Vinci, Robert J. Bauchner, Howard Finkelstein, Jonathan Newby, P. K. Muret-Wagstaff, Sharon Lovejoy, Frederick H., Jr. TI Research During Pediatric Residency Training: Outcome of a Senior Resident Block Rotation SO PEDIATRICS LA English DT Article DE education; residency training; research ID INTERNAL-MEDICINE RESIDENCY; RESEARCH CURRICULUM; RESEARCH EXPOSURE; CLINICAL-RESEARCH; OFFICE SETTINGS; CAREER; PROGRAM; IMPACT; EXPECTATIONS; PERSPECTIVE AB BACKGROUND: The Pediatric Residency Review Committee requires programs to provide a curriculum that advances residents' knowledge of the basic principles of research. In July 2002, the Boston Combined Residency Program instituted a 3-month career-development block (CDB) rotation. During the rotation residents pursue an academic or clinical project under mentorship by a faculty member. OBJECTIVE: Our objective for this study was to evaluate the outcome of the CDB rotation since it was implemented. METHODS: A survey was administered to 165 residents who completed the CDB rotation. RESULTS: Of 165 residents, 136 (82%) responded to the survey. Of 122 residents who reported the type of project they conducted, 59 (48%) completed a clinical/health services project, 24 (20%) completed a project in education or curriculum development, and 7 (6%) worked in basic science. Thirty-five residents (27%) received funding to support their work. Thirty-five residents (26%) presented at national meetings such as the Pediatric Academic Societies Meeting. Fifteen (11%) residents have had manuscripts accepted for publication, and 22 (16%) additional residents have submitted manuscripts for publication. Factors associated with successful publication included having received funding (odds ratio: 3.37 [95% confidence interval: 1.34-8.42]) and the nature of the research project (odds ratio: 3.55 [95% confidence interval: 1.40-9.04]). The majority of residents (84%) stated that the CDB rotation enhanced residency training. CONCLUSIONS: A dedicated academic rotation that includes protected time, senior faculty mentorship, and program funding, can lead to productive research accomplishments by pediatric residents. Support of academic work during residency training may encourage engagement in a variety of academically oriented activities. Pediatrics 2009; 124: 1126-1134 C1 [Vinci, Robert J.; Bauchner, Howard; Newby, P. K.] Boston Univ, Dept Pediat, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Finkelstein, Jonathan; Lovejoy, Frederick H., Jr.] Harvard Univ, Sch Med, Dept Med, Childrens Hosp Boston, Boston, MA USA. [Finkelstein, Jonathan] Harvard Univ, Sch Med, Div Ambulatory Care & Prevent, Boston, MA USA. [Finkelstein, Jonathan] Harvard Pilgrim Hlth Care, Boston, MA USA. [Newby, P. K.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Muret-Wagstaff, Sharon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Vinci, RJ (reprint author), Boston Univ, Dept Pediat, Sch Med, Boston Med Ctr, 818 Harrison Ave, Boston, MA 02118 USA. EM bob.vinci@bmc.org OI Vinci, Robert/0000-0002-2616-1879 NR 40 TC 23 Z9 24 U1 2 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2009 VL 124 IS 4 BP 1126 EP 1134 DI 10.1542/peds.2008-3700 PG 9 WC Pediatrics SC Pediatrics GA 500CI UT WOS:000270274300015 PM 19786447 ER PT J AU Villa-Bellosta, R Levi, M Sorribas, V AF Villa-Bellosta, Ricardo Levi, Moshe Sorribas, Victor TI Vascular smooth muscle cell calcification and SLC20 inorganic phosphate transporters: effects of PDGF, TNF-alpha, and Pi SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE Vascular calcification; Phosphate transport; Pit-1; Endoplasmic reticulum; PDGF ID CHRONIC KIDNEY-DISEASE; NECROSIS-FACTOR-ALPHA; MATRIX GLA PROTEIN; IN-VITRO; COTRANSPORTER; OSTEOPONTIN; EXPRESSION; KINASE; ARTERY; PIT-1 AB Pi transport by vascular smooth muscle cells (VSMC) has been proposed to play an important role in the pathogenesis of vascular calcification. In this study, we have determined the correlation between calcification induced by Pi, platelet-derived growth factor (PDGF)-BB, and tumor necrosis factor-alpha and Pi transport activity in primary cultures of rat aortic VSMC. These agents induced calcification and increased the expression of Cbfa1, Msx2, and Bmp2 osteogene messenger RNA in rat aortic VSMC, while Pi transport rate was not modified per milligram of protein. Only PDGF increased Pi transport when it was expressed per unit of DNA, as PDGF also increased total cell protein by 100%, while DNA content and number of cells were not modified. PDGF increased the expression of the Pi transporter, Pit-1, but membrane protein biotinylation showed that Pit-1 abundance was not modified in the cell surface. Immunofluorescence revealed that, under basal conditions, Pit-1 is only slightly expressed at the cell membrane, but strongly expressed inside the cell. The intracellular signal colocalizes with endoplasmic reticulum (ER) markers, and PDGF increases Pit-1 expression in the ER but not the cell membrane. In conclusion, Pi transport across the plasma membrane does not correlate directly with calcification, but the expression of Pit-1 in the ER opens new possibilities for the study of the pathogenesis of vascular calcification. C1 [Villa-Bellosta, Ricardo; Sorribas, Victor] Univ Zaragoza, Fac Vet, Mol Toxicol Lab, E-50013 Zaragoza, Spain. [Levi, Moshe; Sorribas, Victor] Univ Colorado Denver, Dept Med, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. [Levi, Moshe; Sorribas, Victor] Denver VAMC, Aurora, CO 80045 USA. RP Sorribas, V (reprint author), Univ Zaragoza, Fac Vet, Mol Toxicol Lab, Calle Miguel Servet 177, E-50013 Zaragoza, Spain. EM sorribas@unizar.es FU Spanish Ministry of Education and Science [BFU200606284/BFI]; US National Institute of Health [1 R01 DK066029]; Government of Aragon (Spain) [B086/2007] FX This work was supported by grants BFU200606284/BFI from the Spanish Ministry of Education and Science to VS, 1 R01 DK066029 from the US National Institute of Health to ML, and predoctoral fellowship B086/2007 from the Government of Aragon (Spain) to RVB. NR 34 TC 33 Z9 35 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 2009 VL 458 IS 6 BP 1151 EP 1161 DI 10.1007/s00424-009-0688-5 PG 11 WC Physiology SC Physiology GA 495UB UT WOS:000269919400013 PM 19506901 ER PT J AU Boudreau, RM Hanlon, JT Roumani, YF Studenski, SA Ruby, CM Wright, RM Hilmer, SN Shorr, RI Bauer, DC Simonsick, EM Newman, AB AF Boudreau, Robert M. Hanlon, Joseph T. Roumani, Yazan F. Studenski, Stephanie A. Ruby, Christine M. Wright, Rollin M. Hilmer, Sarah N. Shorr, Ronald I. Bauer, Douglas C. Simonsick, Eleanor M. Newman, Anne B. TI Central nervous system medication use and incident mobility limitation in community elders: the health, aging, and body composition study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE aged; mobility; central nervous system drugs ID LOWER-EXTREMITY FUNCTION; BENZODIAZEPINE USE; OLDER-ADULTS; PHYSICAL PERFORMANCE; DISABILITY; ASSOCIATION; MORTALITY; PEOPLE; DRUGS; WOMEN AB Purpose To evaluate whether CNS medication use in older adults was associated with a higher risk of future incident mobility limitation. Methods This 5-year longitudinal cohort study included 3055 participants from the health, aging and body composition (Health ABC) study who were well-functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and antidepressants) was determined yearly (except year 4) during in-home or in-clinic interviews. Summated standardized daily doses (low, medium, and high) and duration of CNS drug use were computed. Incident mobility limitation was operationalized as two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health behaviors, health status, and common indications for CNS medications. Results Each year at least 13.9% of participants used a CNS medication. By year 6, overall 49% had developed incident mobility limitation. In multivariable models, CNS medication users compared to never users showed a higher risk for incident mobility limitation (adjusted hazard ratio (Adj. HR) 1.28; 95% confidence interval (CI) 1.12-1.47). Similar findings of increased risk were seen in analyses examining dose- and duration-response relationships. Conclusions CNS medication use is independently associated with an increased risk of future incident mobility limitation in community dwelling elderly. Further studies are needed to determine the impact of reducing CNS medication exposure on mobility problems. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Hanlon, Joseph T.; Roumani, Yazan F.; Studenski, Stephanie A.; Ruby, Christine M.; Wright, Rollin M.; Newman, Anne B.] Univ Pittsburgh, Dept Geriatr Med, Sch Med, Pittsburgh, PA 15213 USA. [Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Ruby, Christine M.] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Hanlon, Joseph T.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Hilmer, Sarah N.] Univ Sydney, Sydney, NSW 2006, Australia. [Hilmer, Sarah N.] Royal N Shore Hosp, Sydney, NSW, Australia. [Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst Geriatr Res Edu, Gainesville, FL USA. [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Sch Med, Kaufman Med Bldg Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM hanlonj@dom.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Hilmer, Sarah/0000-0002-5970-1501; Boudreau, Robert/0000-0003-0162-5187 FU NIH, National Institute of Aging [R01AG027017, P30AG024827, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX This study was primarily supported by National Institute of Aging grants and contracts (R01AG027017; P30AG024827, N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106). This research was also supported in part by the Intramural Research program of the NIH, National Institute on Aging. Dr Hanlon and Dr Boudreau have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design was done by Bauer, Hanlon, Boudreau, Newman, Shorr, Simonsick, and Studenski. Data were accumulated by Hanlon, Boudreau, and Newman. Analysis and interpretation of the data were done by Hanlon, Boudreau, Newman, Shorr, Simonsick, Bauer, Ruby, Roumani, Studenski, Wright, and Hilmer. The manuscript was drafted by Hanlon, Boudreau, Roumani, Hilmer, Studenski, Wright, and Simonsick. Critical revision of the manuscript for important intellectual content was done by Hanlon, Boudreau, Newman, Roumani, Hilmer, Shorr, Bauer, Studenski, Ruby, Wright, and Simonsick. Statistical analysis was done by Boudreau, Roumani. Funding was obtained by Hanlon and Newman. The study was supervised by Hanlon and Newman. NR 28 TC 26 Z9 26 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD OCT PY 2009 VL 18 IS 10 BP 916 EP 922 DI 10.1002/pds.1797 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 510GN UT WOS:000271076200006 PM 19585466 ER PT J AU Matros, E Garcia, JA Yaremchuk, MJ AF Matros, Evan Garcia, Jesus A. Yaremchuk, Michael J. TI Changes in Eyebrow Position and Shape with Aging SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the American-Association-of-Plastic-Surgeons CY MAR 21-24, 2009 CL Rancho Mirage, CA SP Amer Assoc Plast Surg ID SUBPERIOSTEAL BROW LIFTS; FIXATION; AGE AB Background: Lack of an objective goal for brow-lift surgery may explain why several articles in the plastic surgery literature conclude that brow lifts produce eyebrows with shape and position that are not aesthetically pleasing. By comparing eyebrow shape and position in both young and mature women, this study provides objective data with which to plan forehead rejuvenating procedures. Methods: Two cohorts of women aged 20 to 30 years and 50 to 60 years were photographed to determine eyebrow position. Measurements were made from a horizontal plane between the medial canthi to three points at the upper eyebrow margin. Exclusion criteria included prior surgery, plucked eyebrows, and botulinum toxin. Results: The eyebrow in the 20- to 30-year-old group (n = 36) was 15.7, 19.8, and 21.3 mm above the medial canthus, pupil, and lateral canthus, respectively. Lateral brow position was significantly higher than the mid brow (p < 0.05). In the 50- to 60-year-old group (n = 34), the brow was 19.1, 22.4, and 22.4 mm above the medial canthus, pupil, and lateral canthus, respectively. At all three points, the brow was higher in older compared with younger subjects. This difference was significant at the medial and mid brow (p < 0.05). Conclusions: Unlike other areas of the body where there is descent of soft tissues, there is paradoxical elevation of eyebrows with aging. These findings explain why surgical elevation of the mid and medial brow provides results that are neither youthful nor aesthetically pleasing. Techniques that selectively elevate the lateral brow are more likely to have a rejuvenating effect on the upper third of the female face. (Plast. Reconstr. Surg. 124: 1296, 2009.) C1 [Yaremchuk, Michael J.] Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, 55 Fruit St,Wang 435, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 28 TC 29 Z9 32 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2009 VL 124 IS 4 BP 1296 EP 1301 DI 10.1097/PRS.0b013e3181b455e8 PG 6 WC Surgery SC Surgery GA 500UZ UT WOS:000270332300034 PM 19935315 ER PT J AU Tonikian, R Xin, XF Toret, CP Gfeller, D Landgraf, C Panni, S Paoluzi, S Castagnoli, L Currell, B Seshagiri, S Yu, HY Winsor, B Vidal, M Gerstein, MB Bader, GD Volkmer, R Cesareni, G Drubin, DG Kim, PM Sidhu, SS Boone, C AF Tonikian, Raffi Xin, Xiaofeng Toret, Christopher P. Gfeller, David Landgraf, Christiane Panni, Simona Paoluzi, Serena Castagnoli, Luisa Currell, Bridget Seshagiri, Somasekar Yu, Haiyuan Winsor, Barbara Vidal, Marc Gerstein, Mark B. Bader, Gary D. Volkmer, Rudolf Cesareni, Gianni Drubin, David G. Kim, Philip M. Sidhu, Sachdev S. Boone, Charles TI Bayesian Modeling of the Yeast SH3 Domain Interactome Predicts Spatiotemporal Dynamics of Endocytosis Proteins SO PLOS BIOLOGY LA English DT Article ID CORTICAL ACTIN CYTOSKELETON; PEPTIDE RECOGNITION MODULES; SACCHAROMYCES-CEREVISIAE; MEDIATED ENDOCYTOSIS; INTERACTION NETWORKS; BUDDING YEAST; BINDING; PROTEOME; CLATHRIN; CYTOKINESIS AB SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast two-hybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes. C1 [Tonikian, Raffi; Xin, Xiaofeng; Gfeller, David; Bader, Gary D.; Boone, Charles] Univ Toronto, Banting & Best Dept Med Res, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. [Tonikian, Raffi; Xin, Xiaofeng; Gfeller, David; Bader, Gary D.; Boone, Charles] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Toret, Christopher P.; Drubin, David G.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Landgraf, Christiane; Volkmer, Rudolf] Charite, Inst Med Immunol, D-13353 Berlin, Germany. [Panni, Simona; Paoluzi, Serena; Castagnoli, Luisa; Cesareni, Gianni] Univ Roma Tor Vergata, Dept Biol, Rome, Italy. [Panni, Simona] Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, Italy. [Currell, Bridget; Seshagiri, Somasekar] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. [Yu, Haiyuan; Vidal, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,CCSB, Boston, MA 02115 USA. [Yu, Haiyuan; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Winsor, Barbara] Univ Strasbourg, UMR7156, Strasbourg, France. [Winsor, Barbara] CNRS, Strasbourg, France. [Gerstein, Mark B.; Kim, Philip M.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. [Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA. [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Cesareni, Gianni] Fdn Santa Lucia, Res Inst, Rome, Italy. [Boone, Charles] Genentech Inc, Dept Prot Engn, San Francisco, CA 94080 USA. RP Tonikian, R (reprint author), Univ Toronto, Banting & Best Dept Med Res, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. EM rve@charite.de; cesareni@uniroma2.it; drubin@berkeley.edu; pi@kimlab.org; sachdev.sidhu@utoronto.ca; charlie.boone@utoronto.ca RI Bader, Gary/C-1176-2009; Xin, Xiaofeng/G-7736-2016; gfeller, david/D-3395-2009; OI Bader, Gary/0000-0003-0185-8861; Xin, Xiaofeng/0000-0002-2439-7183; gfeller, david/0000-0002-3952-0930; panni, simona/0000-0002-7500-4028 FU Canadian Cancer Society [015311]; EU [MRTN-CT-2006-036076]; National Institutes of Health [GM R01 50399]; Swiss National Science Foundation [PBELA-120936]; Canadian Institute of Health Research [MOP-84324]; Italian Association for Cancer Research; EC; Canadian Institutes of Health Research [MOP-84324]; Deutsche Forschungsgemeinschaft [SFB 449] FX CB is supported by the Canadian Cancer Society ( grant # 015311). BW would like to acknowledge EU contract MRTN-CT-2006-036076. DGD was supported by a National Institutes of Health grant GM R01 50399. DG was supported by the Swiss National Science Foundation (grant-PBELA-120936) and the Canadian Institute of Health Research (MOP-84324). GC is supported by the Italian Association for Cancer Research ( AIRC) and the EC FP6 "Interaction Proteome'' integrated project. GDB is supported by the Canadian Institutes of Health Research (MOP-84324). RV thanks the Deutsche Forschungsgemeinschaft (SFB 449) for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 101 Z9 101 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD OCT PY 2009 VL 7 IS 10 AR e1000218 DI 10.1371/journal.pbio.1000218 PG 20 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 522WW UT WOS:000272031800008 PM 19841731 ER PT J AU Selmecki, AM Dulmage, K Cowen, LE Anderson, JB Berman, J AF Selmecki, Anna M. Dulmage, Keely Cowen, Leah E. Anderson, James B. Berman, Judith TI Acquisition of Aneuploidy Provides Increased Fitness during the Evolution of Antifungal Drug Resistance SO PLOS GENETICS LA English DT Article ID CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; EXPERIMENTAL POPULATIONS; MULTIDRUG-RESISTANCE; AZOLE RESISTANCE; CHROMOSOME REASSORTMENTS; WIDESPREAD ANEUPLOIDY; ADAPTIVE EVOLUTION; IN-VITRO; GENES AB The evolution of drug resistance is an important process that affects clinical outcomes. Resistance to fluconazole, the most widely used antifungal, is often associated with acquired aneuploidy. Here we provide a longitudinal study of the prevalence and dynamics of gross chromosomal rearrangements, including aneuploidy, in the presence and absence of fluconazole during a well-controlled in vitro evolution experiment using Candida albicans, the most prevalent human fungal pathogen. While no aneuploidy was detected in any of the no-drug control populations, in all fluconazole-treated populations analyzed an isochromosome 5L [i(5L)] appeared soon after drug exposure. This isochromosome was associated with increased fitness in the presence of drug and, over time, became fixed in independent populations. In two separate cases, larger supernumerary chromosomes composed of i(5L) attached to an intact chromosome or chromosome fragment formed during exposure to the drug. Other aneuploidies, particularly trisomies of the smaller chromosomes (Chr3-7), appeared throughout the evolution experiment, and the accumulation of multiple aneuploid chromosomes per cell coincided with the highest resistance to fluconazole. Unlike the case in many other organisms, some isolates carrying i(5L) exhibited improved fitness in the presence, as well as in the absence, of fluconazole. The early appearance of aneuploidy is consistent with a model in which C. albicans becomes more permissive of chromosome rearrangements and segregation defects in the presence of fluconazole. C1 [Selmecki, Anna M.; Dulmage, Keely; Berman, Judith] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. [Cowen, Leah E.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Anderson, James B.] Univ Toronto, Dept Ecol & Evolutionary Biol, Mississauga, ON L5L 1C6, Canada. [Berman, Judith] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. RP Selmecki, AM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM jberman@umn.edu OI Berman, Judith/0000-0002-8577-0084 FU NIH [R01AI0624273, R01AI075096]; Microbial and Plant Genomics Institute of MN Integrative Fellowship; Burroughs Wellcome Fund Career Award in the Biomedical Sciences; Canada Research Chair in Microbial Genomics and Infectious Disease; Canadian Institutes of Health Research [MOP-86452] FX This research was supported by NIH R01AI0624273 and R01AI075096 to JB; by a Microbial and Plant Genomics Institute of MN Integrative Fellowship to AMS; and by a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, a Canada Research Chair in Microbial Genomics and Infectious Disease, and Canadian Institutes of Health Research Grant MOP-86452 to LEC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 105 Z9 106 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2009 VL 5 IS 10 AR e1000705 DI 10.1371/journal.pgen.1000705 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 522WZ UT WOS:000272032100043 PM 19876375 ER PT J AU Losina, E Toure, H Uhler, LM Anglaret, X Paltiel, AD Balestre, E Walensky, RP Messou, E Weinstein, MC Dabis, F Freedberg, KA AF Losina, Elena Toure, Hapsatou Uhler, Lauren M. Anglaret, Xavier Paltiel, A. David Balestre, Eric Walensky, Rochelle P. Messou, Eugene Weinstein, Milton C. Dabis, Francois Freedberg, Kenneth A. CA ART-LINC Collaboration Int Epidemi CEPAC Int Investigators TI Cost-Effectiveness of Preventing Loss to Follow-up in HIV Treatment Programs: A Cote d'Ivoire Appraisal SO PLOS MEDICINE LA English DT Article ID ANTIRETROVIRAL THERAPY PROGRAMS; RESOURCE-LIMITED SETTINGS; LOWER-INCOME COUNTRIES; SUB-SAHARAN AFRICA; RAPID SCALE-UP; INFECTED ADULTS; SOUTH-AFRICA; TREATMENT SERVICE; CLINICAL IMPACT; POOR SETTINGS AB Background: Data from HIV treatment programs in resource-limited settings show extensive rates of loss to follow-up (LTFU) ranging from 5% to 40% within 6 mo of antiretroviral therapy (ART) initiation. Our objective was to project the clinical impact and cost-effectiveness of interventions to prevent LTFU from HIV care in West Africa. Methods and Findings: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International model to project the clinical benefits and cost-effectiveness of LTFU-prevention programs from a payer perspective. These programs include components such as eliminating ART co-payments, eliminating charges to patients for opportunistic infection-related drugs, improving personnel training, and providing meals and reimbursing for transportation for participants. The efficacies and costs of these interventions were extensively varied in sensitivity analyses. We used World Health Organization criteria of <3x gross domestic product per capita (3x GDP per capita = US$2,823 for Cote d'Ivoire) as a plausible threshold for "cost-effectiveness." The main results are based on a reported 18% 1-y LTFU rate. With full retention in care, projected per-person discounted life expectancy starting from age 37 y was 144.7 mo (12.1 y). Survival losses from LTFU within 1 y of ART initiation ranged from 73.9 to 80.7 mo. The intervention costing US$22/person/year (e. g., eliminating ART co-payment) would be cost-effective with an efficacy of at least 12%. An intervention costing US$77/person/year (inclusive of all the components described above) would be cost-effective with an efficacy of at least 41%. Conclusions: Interventions that prevent LTFU in resource-limited settings would substantially improve survival and would be cost-effective by international criteria with efficacy of at least 12%-41%, depending on the cost of intervention, based on a reported 18% cumulative incidence of LTFU at 1 y after ART initiation. The commitment to start ART and treat HIV in these settings should include interventions to prevent LTFU. C1 [Losina, Elena; Uhler, Lauren M.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Toure, Hapsatou; Anglaret, Xavier; Balestre, Eric; Dabis, Francois] Univ Victor Segalen, ISPED, INSERM, U897, Bordeaux, France. [Anglaret, Xavier; Messou, Eugene] Ctr Prise Charge Rech & Format, Abidjan, Cote Ivoire. [Paltiel, A. David] Yale Univ, New Haven, CT USA. [Walensky, Rochelle P.; Weinstein, Milton C.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Losina, E (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM elosina@partners.org RI Anglaret, Xavier/F-7333-2013; OI Walensky, Rochelle P./0000-0002-8795-379X; Lipsitch, Marc/0000-0003-1504-9213 FU US National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476, P30 AI 060354]; Harvard University Center for AIDS Research [5U01AI069919]; French Agence Nationale de Recherches sur le SIDA et les hepatites [ANRS 12 138 ART-LINC LTFU]; Office of AIDS Research (National Institutes of Health); National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health & Human Development; Doris Duke Charitable Foundation, Clinical Scientist Development FX Supported by the US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, P30 AI 060354 Harvard University Center for AIDS Research, and 5U01AI069919 ART-LINC of IeDEA), the French Agence Nationale de Recherches sur le SIDA et les hepatites (ANRS 12 138 ART-LINC LTFU), the Office of AIDS Research (National Institutes of Health), the National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health & Human Development, and the Doris Duke Charitable Foundation, Clinical Scientist Development Award (to RPW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 41 Z9 41 U1 4 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD OCT PY 2009 VL 6 IS 10 AR e1000173 DI 10.1371/journal.pmed.1000173 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 522XB UT WOS:000272032300016 PM 19859538 ER PT J AU Suri, P Kiely, DK Leveille, SG Frontera, WR Bean, JF AF Suri, Pradeep Kiely, Dan K. Leveille, Suzanne G. Frontera, Walter R. Bean, Jonathan F. TI Trunk Muscle Attributes Are Associated With Balance and Mobility in Older Adults: A Pilot Study SO PM&R LA English DT Article AB Objective: To determine whether trunk muscle attributes are associated with balance and mobility performance among mobility-limited older adults. Design: Cross-sectional analysis of data from a randomized clinical trial. Setting: Outpatient rehabilitation research center. Participants: Community-dwelling older adults (N = 70; mean age 75.9 years) with mobility limitations as defined by the Short Physical Performance Battery (SPPB). Methods: Independent variables included physiologic measures of trunk extension strength, trunk flexion strength, trunk extension endurance, trunk extension endurance, and leg press strength. All measures were well tolerated by the study subjects without the occurrence of any associated injuries or adverse events. The association of each physiologic measure with each outcome was examined by the use of separate multivariate models to calculate the partial variance (R-2) of each trunk and extremity measure. Main Outcome Measurements: Balance measured by the Berg Balance Scale and Unipedal Stance Test and mobility performance as measured by the SPPB. Results: Trunk extension endurance (partial R-2 = .14, P = .02), and leg press strength (partial R-2 = .14, P = .003) accounted for the greatest amount of the variance in SPPB performance. Trunk extension endurance (partial R-2 = .17, P = .007), accounted for the greatest amount of the variance in BBS performance. Trunk extension strength (R-2 = .09, P = .03), accounted for the greatest amount of the variance in UST performance. The variance explained by trunk extension endurance equaled or exceeded the variance explained by limb strength across all three performance outcomes. Conclusions: Trunk endurance and strength can be safely measured in mobility-limited older adults and are associated with both balance and mobility performance. Trunk endurance and trunk strength are physiologic attributes worthy of targeting in the rehabilitative care of mobility-limited older adults. C1 [Suri, Pradeep; Frontera, Walter R.] Harvard Univ, Sch Med, Dept PM&R, Boston, MA 02114 USA. [Suri, Pradeep; Frontera, Walter R.] Spaulding Rehabil Hosp, Boston, MA USA. [Suri, Pradeep] New England Baptist Hosp, Div Res, Boston, MA 02130 USA. [Suri, Pradeep] VA Boston Healthcare Syst, Boston, MA USA. [Kiely, Dan K.] Hebrew SeniorLife, Boston, MA USA. [Leveille, Suzanne G.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02215 USA. [Frontera, Walter R.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Bean, Jonathan F.] Harvard Univ, Sch Med, Dept PM&R, Spaulding Cambridge Outpatient Ctr, Cambridge, MA 02138 USA. RP Suri, P (reprint author), Harvard Univ, Sch Med, Dept PM&R, Boston, MA 02114 USA. EM psuri@caregroup.harvard.edu; jfbean@partners.org RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU American Geriatrics Society/Hartford Foundation; NIH Mentored Clinical Scientist Development Award [K23AG019663-01A2]; Department of PM&R, Harvard Medical School FX 8B, Dennis W. Jahnigen Scholars Career Development Award, American Geriatrics Society/Hartford Foundation, a NIH Mentored Clinical Scientist Development Award (K23AG019663-01A2), and by the Department of PM&R, Harvard Medical School. Clinical trials reg. # NCT00158119 NR 39 TC 31 Z9 32 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD OCT PY 2009 VL 1 IS 10 BP 916 EP 924 DI 10.1016/j.pmrj.2009.09.009 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LN UT WOS:000208412000003 PM 19854420 ER PT J AU Figoni, SF Kunkel, CF Scremin, AME Asher, A Banks, NL Rivera, A Tin, JK Cohen, B AF Figoni, Stephen F. Kunkel, Charles F. Scremin, A. M. Erika Asher, Arash Banks, Norman L. Rivera, Anthony Tin, John K. Cohen, Babak TI Effects of Exercise Training on Calf Tissue Oxygenation in Men With Intermittent Claudication SO PM&R LA English DT Article AB Objective: To determine the effects of exercise training on calf tissue oxygenation in men with peripheral arterial disease and intermittent calf claudication. Design: This pilot study was prospective and longitudinal and used a one-group, pretest-posttest design. Setting: Tertiary care medical center for veterans. Participants: Fifteen male veterans (mean age 69 years) with Fontaine stage Ila peripheral arterial disease and classic intermittent claudication. Main Outcome Measurements: Before and after intervention, participants performed graded treadmill exercise tests while medial calf tissue oxygenation (StO(2), % oxyhemoglobin saturation) was monitored continuously with near-infrared spectroscopy. Intervention: The intervention consisted of a 3-month exercise training program involving 3 sessions per week at the clinic (treadmill walking, calf ergometry) and 2 sessions per week at home (free walking, standing heel raises). Results: After completion of the intervention, participants significantly increased their maximal treadmill exercise time from 7.19 to 11.27 minutes. Mean exercise StO(2) decreased from 29% to 19% saturation, StO(2) X time area increased from 421% . mm to 730% . min StO(2) nadir, and StO(2) recovery time did not change significantly. Conclusions: After the exercise intervention, the improved treadmill walking performance was accompanied by greater calf tissue deoxygenation during exercise. Given the continued presence of ischemia, this finding may represent increased capillarization and diffusion-based enhancement of arteriovenous O-2 extraction. C1 [Figoni, Stephen F.; Kunkel, Charles F.; Scremin, A. M. Erika; Cohen, Babak] VA W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Phys Med & Rehabil Serv, Los Angeles, CA USA. [Kunkel, Charles F.; Scremin, A. M. Erika] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Asher, Arash; Banks, Norman L.; Rivera, Anthony; Tin, John K.] Univ Calif Los Angeles, VA Greater Los Angeles Phys Med & Rehabil Residen, Los Angeles, CA USA. RP Figoni, SF (reprint author), VA W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Phys Med & Rehabil Serv, 11301 Wilshire Blvd, Los Angeles, CA USA. EM sfigoni@gmail.com FU Rehabilitation Research and Development Service, Department of Veterans Affairs [B3644P] FX 8, Grant #B3644P from the Rehabilitation Research and Development Service, Department of Veterans Affairs NR 42 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD OCT PY 2009 VL 1 IS 10 BP 932 EP 940 DI 10.1016/j.pmrj.2009.08.453 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LN UT WOS:000208412000005 PM 19854422 ER PT J AU Kirschner, KL Breslin, ML Iezzoni, LI Sandel, E AF Kirschner, Kristi L. Breslin, Mary Lou Iezzoni, Lisa I. Sandel, Elizabeth TI Attending to Inclusion: People With Disabilities and Health-Care Reform SO PM&R LA English DT Editorial Material C1 [Kirschner, Kristi L.] Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Chicago, IL 60611 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Cambridge, MA 02138 USA. [Sandel, Elizabeth] Kaiser Fdn Rehabil Ctr, Vallejo, CA USA. RP Kirschner, KL (reprint author), Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Chicago, IL 60611 USA. EM kkirschner@ric.org NR 5 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD OCT PY 2009 VL 1 IS 10 BP 957 EP 959 DI 10.1016/j.pmrj.2009.09.001 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LN UT WOS:000208412000008 PM 19854424 ER PT J AU Steele, AD Zhou, ZP Jackson, WS Zhu, CN Auluck, P Moskowitz, MA Chesselet, MF Lindquist, S AF Steele, Andrew D. Zhou, Zhipeng Jackson, Walker S. Zhu, Chunni Auluck, Pavan Moskowitz, Michael A. Chesselet, Marie-Francoise Lindquist, Susan TI Context dependent neuroprotective properties of prion protein (PrP) SO PRION LA English DT Article DE neurodegeneration; protein misfolding; PrP; home cage; stroke ID ISCHEMIC BRAIN-INJURY; HUMAN ALPHA-SYNUCLEIN; TRANSGENIC MICE; NEUROFIBRILLARY TANGLES; NEURODEGENERATIVE DISORDERS; OXIDATIVE STRESS; MOUSE MODELS; TAU-PROTEIN; DISEASE; MUTATION AB Although it has been known for more than twenty years that an aberrant conformation of the prion protein (PrP) is the causative agent in prion diseases, the role of PrP in normal biology is undetermined. Numerous studies have suggested a protective function for PrP, including protection from ischemic and excitotoxic lesions and several apoptotic insults. On the other hand, many observations have suggested the contrary, linking changes in PrP localization or domain structure-independent of infectious prion conformation-to severe neuronal damage. Surprisingly, a recent report suggests that PrP is a receptor for toxic oligomeric species of a-beta, a pathogenic fragment of the amyloid precursor protein, and likely contributes to disease pathogenesis of Alzheimer disease. We sought to access the role of PrP in diverse neurological disorders. First, we confirmed that PrP confers protection against ischemic damage using an acute stroke model, a well characterized association. After ischemic insult, PrP knockouts had dramatically increased infarct volumes and decreased behavioral performance compared to controls. To examine the potential of PrP's neuroprotective or neurotoxic properties in the context of other pathologies, we deleted PrP from several transgenic models of neurodegenerative disease. Deletion of PrP did not substantially alter the disease phenotypes of mouse models of Parkinson disease or tauopathy. Deletion of PrP in one of two Huntington disease models tested, R6/2, modestly slowed motor deterioration as measured on an accelerating rotarod but otherwise did not alter other major features of the disease. Finally, transgenic overexpression of PrP did not exacerbate the Huntington motor phenotype. These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein. C1 [Steele, Andrew D.; Jackson, Walker S.; Auluck, Pavan; Lindquist, Susan] MIT, Howard Hughes Med Inst, Whitehead Inst Biomed Res, Cambridge, MA USA. [Zhou, Zhipeng; Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Zhu, Chunni; Chesselet, Marie-Francoise] Univ Calif Los Angeles, David Geffen Sch Med, Reed Neurol Res Ctr B114, Dept Neurol, Los Angeles, CA 90095 USA. [Zhu, Chunni; Chesselet, Marie-Francoise] Univ Calif Los Angeles, David Geffen Sch Med, Reed Neurol Res Ctr B114, Dept Neurobiol, Los Angeles, CA 90095 USA. [Auluck, Pavan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Auluck, Pavan] Harvard Univ, Sch Med, Boston, MA USA. RP Lindquist, S (reprint author), MIT, Howard Hughes Med Inst, Whitehead Inst Biomed Res, Cambridge, MA USA. EM Lindquist_admin@wi.mit.edu FU Ellison Medical Research Foundation; Whitaker Health Sciences FX We are grateful to Artur Topolszki for a mouse colony management; to Karen Allendoerfer, Chris Pacheco and Keith Gunapala for comments of the manuscript; to Michael Hutton, David Westaway and Jiyan Ma for helpful advice; and to Mike Brown of the MIT Center for Cancer Research for histology. Funding was provided by the Ellison Medical Research Foundation (to S. L.) and a Whitaker Health Sciences graduate student fellowship (to A. D. S.). S. L. is an investigator of the Howard Hughes Medical Institute. NR 61 TC 21 Z9 21 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1933-6896 J9 PRION JI Prion PD OCT-DEC PY 2009 VL 3 IS 4 BP 240 EP 249 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 627RX UT WOS:000280061100011 PM 19901559 ER PT J AU Post, RM Wozniak, J AF Post, Robert M. Wozniak, Janet TI Survey of Expert Treatment Approaches for Children with Bipolar Disorder-not otherwise specified and Bipolar-I Presentations SO PSYCHIATRIC ANNALS LA English DT Article ID PSYCHIATRIC-DISORDERS; COMBINATION LITHIUM; DIVALPROEX SODIUM; YOUNG-CHILDREN; DOUBLE-BLIND; EARLY-ONSET; ADOLESCENTS; MANIA; TRIAL; PHENOMENOLOGY C1 [Post, Robert M.] George Washington Univ, Sch Med, Washington, DC 20052 USA. [Post, Robert M.] Bipolar Collaborat Network, Bethesda, MD USA. [Wozniak, Janet] Massachusetts Gen Hosp, Pediat Bipolar Disorder Clin & Res Program, Boston, MA 02114 USA. [Wozniak, Janet] Harvard Univ, Sch Med, Boston, MA USA. RP Post, RM (reprint author), 5415 W Cedar Lane,Suite 201B, Bethesda, MD USA. EM robert.post@speakeasy.net NR 35 TC 2 Z9 2 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 2009 VL 39 IS 10 BP 887 EP 895 DI 10.3928/00485718-20090924-07 PG 9 WC Psychiatry SC Psychiatry GA 507IY UT WOS:000270847300004 ER PT J AU Brekke, JS Hoe, M Green, MF AF Brekke, J. S. Hoe, M. Green, M. F. TI Neurocognitive change, functional change and service intensity during community-based psychosocial rehabilitation for schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Functional change; neurocognitive change; psychosocial rehabilitation; schizophrenia ID SEVERE MENTAL-ILLNESS; CASE-MANAGEMENT; 1ST-EPISODE SCHIZOPHRENIA; MEASUREMENT INVARIANCE; COGNITIVE REMEDIATION; SUBJECTIVE EXPERIENCE; SOCIAL COGNITION; RATING-SCALE; FOLLOW-UP; DEFICITS AB Background. This study examined the magnitude of neurocognitive change during 1 year of community-based psychosocial intervention, whether neurocognitive change and functional change were linked, and how neurocognitive change combined with service intensity to facilitate functional change. Method. A total of 130 individuals diagnosed with schizophrenia were recruited upon admission to four community-based psychosocial rehabilitation programs. Subjects were assessed at baseline, 6 and 12 months oil role functioning and symptom measures. Neurocognition was measured at baseline and 12 months. Service intensity was the number of days of treatment attendance during the study period. Latent mean difference tests and Latent Growth Curve Models (LCGMs) were used to examine the Study hypotheses. Results. There was statistically and clinically significant functional improvement over 12 months. Neurocognition improved significantly over time. Seventy-six (58%) of the sample showed neurocognitive improvement and 54 (42%) did not. There was a significant rate of functional enhancement in the neurocognitive improver group. There was a non-significant rate of functional change in the neurocognitive non-improver group. Neurocognitive improvers showed functional improvement that was 350% greater than neurocognitive non-improvers. Service intensity did not vary between neurocognitive improvers and non-improvers but there was a strong interaction between neurocognitive improvement, service intensity and rate Of functional improvement Such that service intensity was strongly related to functional improvement for neurocognitive improvers but not for neurocognitive non-improvers. Medication usage and symptomatology did not confound these findings. Conclusions. These findings suggest that neurocognitive improvement may be a foundation for functional change and treatment responsiveness during COMM Unity-based psychosocial rehabilitation for individuals With schizophrenia. C1 [Brekke, J. S.; Hoe, M.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Green, M. F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Brekke, JS (reprint author), Univ So Calif, Sch Social Work, MC 0411, Los Angeles, CA 90089 USA. EM brekke@usc.edu FU National Institute of Mental Health [R-01 MH53282] FX This research was supported by grant no. R-01 MH53282 from the National Institute of Mental Health awarded to J.S.B. NR 65 TC 23 Z9 25 U1 1 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2009 VL 39 IS 10 BP 1637 EP 1647 DI 10.1017/S003329170900539X PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 499XQ UT WOS:000270260500008 PM 19243648 ER PT J AU Thompson, WL Slotnick, SD Burrage, MS Kosslyn, SM AF Thompson, William L. Slotnick, Scott D. Burrage, Marie S. Kosslyn, Stephen M. TI Two Forms of Spatial Imagery: Neuroimaging Evidence SO PSYCHOLOGICAL SCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; MENTAL ROTATION; NEURAL MECHANISMS; MEMORY; VISUALIZERS; ABILITIES; SKILLS; AREAS AB Spatial imagery may be useful in such tasks as interpreting graphs and solving geometry problems, and even in performing surgery. This study provides evidence that spatial imagery is not a single faculty; rather, visualizing spatial location and mentally transforming location rely on distinct neural networks. Using 3-T functional magnetic resonance imaging, we tested 16 participants (8 male, 8 female) in each of two spatial imagery tasks-one that required visualizing location and one that required mentally rotating stimuli. The same stimuli were used in the two tasks. The location-based task engendered more activation near the occipito-parietal sulcus, medial posterior cingulate, and precuneus, whereas the transformation task engendered more activation in superior portions of the parietal lobe and in the postcentral gyrus. These differences in activation provide evidence that there are at least two different types of spatial imagery. C1 [Kosslyn, Stephen M.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Slotnick, Scott D.] Boston Coll, Boston, MA USA. [Kosslyn, Stephen M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kosslyn, SM (reprint author), Harvard Univ, Dept Psychol, 830 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM stephen_kosslyn@harvard.edu NR 23 TC 22 Z9 23 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD OCT PY 2009 VL 20 IS 10 BP 1245 EP 1253 PG 9 WC Psychology, Multidisciplinary SC Psychology GA 504BU UT WOS:000270589300012 PM 19765238 ER PT J AU Yehuda, R Bierer, LM Sarapas, C Makotkine, I Andrew, R Seckl, JR AF Yehuda, Rachel Bierer, Linda M. Sarapas, Casey Makotkine, Iouri Andrew, Ruth Seckl, Jonathan R. TI Cortisol metabolic predictors of response to psychotherapy for symptoms of PTSD in survivors of the World Trade Center attacks on September 11, 2001 SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Posttraumatic stress disorder; Cortisol; Cortisol metabolites; Glucocorticoid metabolism; Biological markers; Psychotherapy; 5 alpha-Reductase; 5 alpha-Tetrahydrocortisol (5 alpha-THF) ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; COGNITIVE-BEHAVIORAL THERAPY; HOLOCAUST SURVIVORS; SALIVARY CORTISOL; PLASMA-CORTISOL; SEXUAL ABUSE; HPA-AXIS; IN-VIVO AB Background: A proportion of subjects with symptoms of posttraumatic stress disorder (PTSD) are unresponsive to specialized psychotherapy, but a biological basis for this has not been described. To observe whether differences in cortisol or its metabolites predict or correlate with response to therapy for PTSD symptoms, cortisol and its metabolites were measured from urine samples at pre-treatment, at the conclusion of psychotherapy, and at 3-month follow-up. Methods: 28 survivors of the World Trade Center attacks on September 11, 2001 seeking psychological treatment for PTSD symptoms received four sessions of either exposure therapy or supportive counseling, followed by up to 10 sessions of prolonged exposure in a specialized PTSD treatment program at a private hospital serving the New York City metropolitan area. 24-h mean integrated cortisol excretion was assessed by radioimmunoassay (RIA); urinary free cortisol and metabolites cortisone, 5 alpha-tetrahydrocortisol (5 alpha-THF), 5 beta-tetrahydrocortisol, and tetrahydrocortisone were assessed by gas chromatography-mass spectrometry (GC-MS); and indices of enzyme activity for 5 alpha- and 5 beta-reductase and for the 11 beta-hydroxysteroid dehydrogenases were derived from the metabolite and glucocorticoid measures. Results: 5 alpha-Reductase activity was significantly tower at pre-treatment among non-responders, whereas there were no significant pre-treatment differences between responders and non-responders in any other hormone or metabolite level. In repeated measures analyses across the three time points, 5 alpha-reductase activity, as well as 5 alpha-THF and total glucocorticoids, significantly differed between responders and non-responders. For urinary cortisol measured by RIA, there was a significant group x time interaction indicating that, although not different at pre-treatment, urinary cortisol levels declined over time in the non-responder group, such that by follow-up, towered cortisol significantly distinguished non-responders from responders. Indices of 5 alpha-reductase activity, including 5 alpha-THF and total glucocorticoids, were significantly negatively correlated with avoidance symptom severity at pre-treatment. At follow-up, indices of 5 alpha-reductase activity were significantly negatively correlated with severity of all three PTSD symptom clusters and with total PTSD severity scores. Conclusion: Lower 5 alpha-reductase activity is associated with avoidance severity and predicts non-responsiveness to psychological treatment for PTSD symptomatology. Relatively diminished 5 alpha-reductase activity may mark a state of primary vulnerability, perhaps via attenuated peripheral catabolism of cortisol resulting in the suppression of hypothalamic-pituitary-ad renal axis responsiveness. Lower cortisol levels appear later in the progression to chronic, treatment-resistant PTSD. Published by Elsevier Ltd. C1 [Yehuda, Rachel; Bierer, Linda M.; Sarapas, Casey; Makotkine, Iouri] Mt Sinai Sch Med, Traumat Stress Studies Div, Bronx, NY 10468 USA. [Yehuda, Rachel; Bierer, Linda M.; Sarapas, Casey; Makotkine, Iouri] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Andrew, Ruth; Seckl, Jonathan R.] Univ Edinburgh, Queens Med Res Inst, Endocrinol Unit, Edinburgh EH16 4TJ, Midlothian, Scotland. RP Yehuda, R (reprint author), Mt Sinai Sch Med, Traumat Stress Studies Div, Psychiat 116-A OOMH,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov RI Seckl, Jonathan/C-3555-2013; Andrew, Ruth/C-2727-2008 FU NCRR NIH HHS [M01 RR000071, M01 RR000071-458256]; NIMH NIH HHS [R01MH064104-01, R56 MH077321, R56 MH077321-01] NR 63 TC 51 Z9 53 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD OCT PY 2009 VL 34 IS 9 BP 1304 EP 1313 DI 10.1016/j.psyneuen.2009.03.018 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 506LY UT WOS:000270777500005 PM 19411143 ER PT J AU Golier, JA Schmeidler, J Yehuda, R AF Golier, Julia A. Schmeidler, James Yehuda, Rachel TI Pituitary response to metyrapone in Gulf War veterans: Relationship to deployment, PTSD and unexplained health symptoms SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Medically unexplained illness; Gulf War syndrome; Stress; ACTH; Cortisol; Metyrapone ID POSTTRAUMATIC-STRESS-DISORDER; OPERATION DESERT-STORM; MULTISYMPTOM ILLNESS; MILITARY SERVICE; CORTISOL; HORMONE; ACTH; SYMPTOMATOLOGY; DEXAMETHASONE; SPECTROSCOPY AB Objective: Gulf War deployment has been associated with a distinct neuroendocrine profile characterized by low 24 h basal ACTH levels and enhanced cortisol and ACTH suppression to low-dose dexamethasone. The metyrapone stimulation test was performed to further characterize hypothalamic-pituitary activity in Gulf War veterans (GWV) and its relationship to unexplained medical symptoms and post-traumatic stress disorder (PTSD). Method: Eleven GWV without PTSD, 18 GWV with PTSD and 15 healthy subjects not exposed to the Gulf War theater (non-exposed) underwent the metyrapone stimulation test, which inhibits cortisol synthesis, impairs cortisol-mediated negative feedback inhibition and in turn increases levels of ACTH and 11-deoxycortisol, a cortisol precursor. These hormones were measured at baseline (7:00 a.m.) and at intervals (from 8:00a.m. to 4:00 p.m.) following the administration of metyrapone 750 mg orally at 7:05 a.m. and at 10:05 a.m. Results: There were group differences in the ACTH response despite similar cortisol and 11-deoxycortisol responses to metyrapone. GWV without PTSD had a significantly attenuated ACTH response compared to non-exposed subjects; GWV with PTSD had a significantly higher ACTH response than GWV without PTSD but did not differ from non-exposed subjects. Among GWV, unexplained medical health symptoms (e.g., neurological, musculoskeletal, cardiac, and pulmonary symptoms) and PTSD symptoms were significantly positively associated with the ACTH response to metyrapone. Conclusion: Gulf War deployment is associated with a substantially lower ACTH response to metyrapone. In contrast, unexplained health symptoms and PTSD in Gulf War veterans are associated with relatively greater hypothalamic-pituitary activity which may reflect increased CRF activity and is evident only in consideration of deployment effects. This pattern of differences suggests either that Gulf War deployment and its associated exposures results in enduring changes in pituitary function or that reduced hypothalamic-pituitary activity protects against the development of PTSD and other deployment-related health problems. Published by Elsevier Ltd. C1 [Golier, Julia A.] James J Peters VA Med Ctr, OOMH, Dept Psychiat, Bronx, NY 10468 USA. [Golier, Julia A.; Schmeidler, James; Yehuda, Rachel] Mt Sinai Sch Med, New York, NY USA. RP Golier, JA (reprint author), James J Peters VA Med Ctr, OOMH, Dept Psychiat, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM julia.golier@va.gov FU VA/DoD; VA MERIT; National Institute of Health [5 M01 RR00071] FX This work was supported by a VA/DoD and VA MERIT award to Dr. Golier and by a grant (5 M01 RR00071) for the Mount Sinai General Clinical Research Center from the National Institute of Health. The authors also gratefully acknowledge the time and effort of the veterans who participated in this study. NR 51 TC 12 Z9 12 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD OCT PY 2009 VL 34 IS 9 BP 1338 EP 1345 DI 10.1016/j.psyneuen.2009.04.004 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 506LY UT WOS:000270777500008 PM 19446401 ER PT J AU Ghasemi, M Montaser-Kouhsari, L Shafaroodi, H Nezami, BG Ebrahimi, F Dehpour, AR AF Ghasemi, Mehdi Montaser-Kouhsari, Laleh Shafaroodi, Hamed Nezami, Behtash Ghazi Ebrahimi, Farzad Dehpour, Ahmad Reza TI NMDA receptor/nitrergic system blockage augments antidepressant-like effects of paroxetine in the mouse forced swimming test SO PSYCHOPHARMACOLOGY LA English DT Article DE Paroxetine; N-methyl-D-aspartate (NMDA) antagonists; Nitric oxide; Nitric oxide synthase; Depression; Forced swimming test ID SEROTONIN REUPTAKE INHIBITORS; TAIL SUSPENSION TEST; OXIDE SYNTHASE INHIBITORS; MAJOR DEPRESSIVE DISORDER; D-ASPARTATE RECEPTOR; NITRIC-OXIDE; CONTROLLED-TRIAL; ANIMAL-MODELS; POTENTIAL ANTIDEPRESSANTS; EXHIBIT ANTIDEPRESSANT AB In this study, we evaluated the involvement of N-methyl-d-aspartate receptor (NMDAR)/nitric oxide (NO) system on the antidepressant-like effects of paroxetine in the mouse forced swimming test. Swim sessions were conducted by placing mice in individual glass cylinders filled with water for 6 min. The duration of behavioral immobility during the last 4 min of the test was evaluated. Paroxetine (8 and 16 mg/kg, intraperitoneal [i.p.]) significantly reduced the immobility times of mice, whereas lower doses (2 and 4 mg/kg) had no effect. NMDA antagonists MK-801 (0.1 and 0.25 mg/kg, i.p.) and ifenprodil (1 and 3 mg/kg, i.p.) and the NO synthase inhibitor N-G-l-arginine methyl ester (L-NAME; 30 and 100 mg/kg, i.p.) significantly decreased the immobility time. Lower doses of MK-801 (0.01 and 0.05 mg/kg), ifenprodil (0.1 and 0.5 mg/kg), and L-NAME (10 mg/kg) had no effect. Combined treatment of subeffective doses of paroxetine (4 mg/kg) and MK-801 (0.05 mg/kg), ifenprodil (0.5 mg/kg), and L-NAME (10 mg/kg) robustly exerted an antidepressant-like effect. The noneffective dose of a NO precursor l-arginine (750 mg/kg, i.p.) prevented the antidepressant-like effect of paroxetine (30 mg/kg). We suggested, for the first time, a possible role for NMDAR/NO signaling in the antidepressant-like effects of paroxetine, providing a new approach for the treatment of depression. C1 [Ghasemi, Mehdi; Montaser-Kouhsari, Laleh; Nezami, Behtash Ghazi; Ebrahimi, Farzad; Dehpour, Ahmad Reza] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran. [Montaser-Kouhsari, Laleh; Shafaroodi, Hamed] Islamic Azad Univ, Tehran Med Branch, Dept Pharmacol, Tehran, Iran. [Ebrahimi, Farzad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Dehpour, AR (reprint author), Univ Tehran Med Sci, Sch Med, Dept Pharmacol, POB 13145-784, Tehran, Iran. EM m82_ghasemi@yahoo.com; dehpour@yahoo.com OI dehpour, ahmad reza/0000-0002-8001-5565 NR 84 TC 41 Z9 42 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2009 VL 206 IS 2 BP 325 EP 333 DI 10.1007/s00213-009-1609-1 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 488WM UT WOS:000269381000015 PM 19609507 ER PT J AU Kilbourne, AM Perron, BE Mezuk, B Welsh, D Ilgen, M Bauer, MS AF Kilbourne, Amy M. Perron, Brian E. Mezuk, Briana Welsh, Deborah Ilgen, Mark Bauer, Mark S. TI Co-occurring Conditions and Health-Related Quality of Life in Patients With Bipolar Disorder SO PSYCHOSOMATIC MEDICINE LA English DT Article DE bipolar disorder; comorbidity; health-related quality of life ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; CARE UTILIZATION; MOOD DISORDERS; GLOBAL BURDEN; II SUBTYPES; FOLLOW-UP; COSTS; COMORBIDITY; OUTCOMES AB Objective: To assess changes in health-related quality of life (HRQOL) and to determine whether co-occurring substance use and medical comorbidities were associated with worse HRQOL over a 1-year period in a naturalistic sample of patients with bipolar disorder Method: Patients enrolled in the Continuous Improvement for Veterans in Care: Mood Disorders (CIVIC-MD), a large prospective study from July 2004 to July 2006, completed baseline and follow-up assessments related to bipolar symptoms, comorbidity, and Short Form 12 HRQOL assessment at baseline and at I year later. Predictors of changes in HRQOL mental and physical health component scores were determined, using multivariable linear regression models and path analyses. Results: Of 334 participants, the mean age was 49 years (standard deviation [SD] = 10.1 years., range = 21-78 years), 15.9% women, and 10.8% African American. At baseline, 19.8% reported hazardous drinking, 25.5% reported illicit drug use, and the mean number of co-occurring medical conditions was 2.70 (SD = 2.02). Illicit drug use was associated with worse mental HRQOL (beta = -2.01; p < 05), and increased number of medical comorbidities was significantly associated with worse physical HRQOL over time (beta = -0.7 1; p < .01). Depressive symptoms exhibited a strong and consistent influence on mental health scores over time, but path analyses revealed that they did not seem to mediate effects of comorbidities oil lower HRQOL. Conclusions: Illicit drug use and medical comorbidity negatively affected mental HRQOL over time, independent of bipolar symptoms, suggesting the need for interventions that address physical health and drug treatment needs for patients with bipolar disorder C1 [Kilbourne, Amy M.; Perron, Brian E.; Mezuk, Briana; Welsh, Deborah; Ilgen, Mark] VA Ann Arbor Hlth Serv Res & Dev, Ann Arbor, MI USA. [Kilbourne, Amy M.; Perron, Brian E.; Mezuk, Briana; Welsh, Deborah; Ilgen, Mark] Natl Serious Mental Illness Treatment Res & Evalu, Ann Arbor, MI USA. [Kilbourne, Amy M.; Ilgen, Mark] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Perron, Brian E.] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Mezuk, Briana] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Harvard S Shore Psychiat Residency Training Progr, Boston, MA USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. RP Kilbourne, AM (reprint author), VA Ann Arbor HSRD SMITREC, 11H,2215 Fuller Rd, Ann Arbor, MI 48105 USA. OI Mezuk, Briana/0000-0003-1798-2285 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 02-283, IIR 07-115] FX This research was supported by Grants IIR 02-283 (A.M.K.) and IIR 07-115 (A M K) from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service The views expressed in this article are those. of the authors and do not necessarily represent the views of the Department of Veterans Affairs NR 34 TC 9 Z9 9 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2009 VL 71 IS 8 BP 894 EP 900 DI 10.1097/PSY.0b013e3181b49948 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 512CZ UT WOS:000271222300012 PM 19661187 ER PT J AU Seale, MK Catalano, OA Saini, S Hahn, PF Sahani, DV AF Seale, Melanie K. Catalano, Onofrio A. Saini, Sanjay Hahn, Peter F. Sahani, Dushyant V. TI Hepatobiliary-specific MR Contrast Agents: Role in Imaging the Liver and Biliary Tree SO RADIOGRAPHICS LA English DT Article ID FOCAL NODULAR HYPERPLASIA; MAGNETIC-RESONANCE CHOLANGIOGRAPHY; MNDPDP-ENHANCED MRI; GD-EOB-DTPA; GADOBENATE DIMEGLUMINE; HEPATOCELLULAR-CARCINOMA; MANGAFODIPIR-TRISODIUM; SPIRAL CT; COLORECTAL-CANCER; GADOPENTETATE DIMEGLUMINE AB Hepatobiliary-specific contrast agents are one of several classes of contrast agents available for magnetic resonance (MR) imaging of the liver. These agents are taken up by functioning hepatocytes and excreted in the bile, and their paramagnetic properties cause shortening of the longitudinal relaxation time (T1) of the liver and biliary tree. The three contrast agents that have been developed are mangafodipir trisodium (Mn-DPDP), gadobenate dimeglumine (Gd-BOPTA), and gadoxetic acid (Gd-EOB-DTPA). These three MR contrast agents vary in mode of administration and dose, mechanism of cellular uptake, degree of excretion through the biliary pathway, and imaging characteristics. In the liver, hepatobiliary-specific agents can be used to improve lesion detection, to characterize lesions as hepatocellular or nonhepatocellular, and to specifically characterize some hepatocellular lesions, notably focal nodular hyperplasia. Biliary excretion of these agents can be used to evaluate the anatomic structure and function of the biliary tree. In the future, hepatobiliary-specific contrast agents may have wider applications, such as grading of cirrhosis and quantification of liver function. (C) RSNA, 2009 . radiographics.rsna.org C1 [Seale, Melanie K.; Catalano, Onofrio A.; Saini, Sanjay; Hahn, Peter F.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 50 TC 150 Z9 171 U1 2 U2 14 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2009 VL 29 IS 6 BP 1725 EP U240 DI 10.1148/rg.296095515 PG 25 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512US UT WOS:000271277400013 PM 19959518 ER PT J AU Johnson, AJ Chen, MYM Swan, JS Applegate, KE Littenberg, B AF Johnson, Annette J. Chen, Michael Y. M. Swan, J. Shannon Applegate, Kimberly E. Littenberg, Benjamin TI Cohort Study of Structured Reporting Compared with Conventional Dictation SO RADIOLOGY LA English DT Article AB Purpose: To determine if radiology residents who used a structured reporting system (SRS) produced higher quality reports than residents who used conventional free-text dictation to report cranial magnetic resonance (MR) imaging in patients suspected of having a stroke. Materials and Methods: The study was approved by an institutional review board and was HIPAA compliant; informed consent was obtained. This study included residents, with 16 in the control group and 18 in the intervention group. For phase 1, each subject reviewed the same set of 25 brain MR imaging cases and dictated the cases by using free-text conventional dictation. For phase 2, 4 months later, the control group repeated the same process, whereas the intervention group reread the same MR imaging cases by using SRS to create reports. Resident-generated reports were graded for accuracy and completeness by a neuroradiologist on the basis of consensus interpretations and criterion standard diagnoses as established with at least 6 months of clinical follow-up, imaging follow-up, and/or histologic examination where appropriate. Accuracy and completeness scores were analyzed by using a Wilcoxon signed rank test for paired data and a Mann-Whitney U test for nonpaired data. Intervention group residents were surveyed regarding their opinions of SRS. Results: For phase 1 reports, no significant difference in accuracy or completeness scores between control and intervention groups was found. Decreases in accuracy (91.5 to 88.7) and completeness (68.7 to 54.3) scores for phase 2 compared with phase 1 for the intervention group were found; increases in accuracy (91.4 to 92.4) and completeness (67.8 to 71.7) scores for phase 2 compared with phase 1 for the control group were found (all P values < .001). The most common complaints were that the SRS was overly constraining with regard to report content and was time-consuming to use. Conclusion: While there are many potential benefits of structuring radiology reports, such changes cannot be assumed to improve report accuracy or completeness. Any SRS should be tested for effect on intrinsic report quality. (C) RSNA, 2009 C1 [Johnson, Annette J.; Chen, Michael Y. M.] Wake Forest Univ, Dept Radiol, Sch Med, Winston Salem, NC 27157 USA. [Swan, J. Shannon] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Applegate, Kimberly E.] Indiana Univ Purdue Univ, Dept Radiol, Educ & Res Inst, Indianapolis, IN 46202 USA. [Littenberg, Benjamin] Univ Vermont, Dept Med, Burlington, VT USA. RP Johnson, AJ (reprint author), Wake Forest Univ, Dept Radiol, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM anjohnso@wfubmc.edu OI Littenberg, Benjamin/0000-0002-7647-1808 NR 26 TC 37 Z9 37 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2009 VL 253 IS 1 BP 74 EP 80 DI 10.1148/radiol.2531090138 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512UB UT WOS:000271275200011 PM 19709993 ER PT J AU Abujudeh, HH Kaewlai, R Kagan, A Chibnik, LB Nazarian, RM High, WA Kay, J AF Abujudeh, Hani H. Kaewlai, Rathachai Kagan, Anna Chibnik, Lori B. Nazarian, Rosalynn M. High, Whitney A. Kay, Jonathan TI Nephrogenic Systemic Fibrosis after Gadopentetate Dimeglumine Exposure: Case Series of 36 Patients SO RADIOLOGY LA English DT Article ID CONTRAST AGENTS; RENAL-FAILURE; GADOLINIUM; DERMOPATHY; GADODIAMIDE; TISSUE; RISK; ASSOCIATION; INVOLVEMENT; DEPOSITION AB Purpose: To retrospectively assess the association between gadopentetate dimeglumine exposure at magnetic resonance imaging and the development of nephrogenic systemic fibrosis (NSF). Materials and Methods: This HIPAA-compliant study had institutional review board approval. Informed consent was waived. A search of medical and pathologic records was performed to identify patients with NSF that was diagnosed between January 1998 and December 2007. Patients with known exposure to gadolinium-based contrast agents other than gadopentetate dimeglumine were excluded. Medical records were then reviewed for gadopentetate dimeglumine exposure, renal status, concomitant diseases, timing of NSF symptom onset, date of NSF diagnosis, and clinical outcome. Skin gadolinium deposition was assessed for those patients with adequate available tissue. Spearman rank correlations were estimated to assess the relationship between the dose of gadopentetate dimeglumine and the time to onset of NSF. Results: Thirty-six patients (mean age, 62.6 years; range, 30-83 years) had been exposed to gadopentetate dimeglumine prior to NSF onset. All had stage 5 chronic kidney disease and all but one were undergoing dialysis at the time of exposure. NSF developed within 3 months after the last gadopentetate dimeglumine exposure (range, 1-59 months) in 21 (66%) of 32 patients. The patients had been exposed to median cumulative gadopentetate dimeglumine volumes of 35, 40, 85, and 117.5 mL over the 3, 12, and 24 months and up to 11 years preceding the onset of NSF, respectively. Patients who received higher cumulative and total gadopentetate dimeglumine doses had a higher risk of developing NSF than did those who received lower doses (odds ratio = 1.2). Twenty (56%) of 36 patients died, with a median interval of 18 months between NSF symptom onset and death. Conclusion: NSF develops in patients with renal impairment after exposure to gadopentetate dimeglumine in a dose- and time-dependent manner. (C) RSNA, 2009 C1 [Abujudeh, Hani H.; Kaewlai, Rathachai] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kagan, Anna] Baylor Coll Med, Dept Internal Med, Houston, TX 77030 USA. [Chibnik, Lori B.] Brigham & Womens Hosp, Clin Sci Sect, Boston, MA 02115 USA. [High, Whitney A.] Univ Colorado, Hlth Sci Ctr, Dept Dermatol, Denver, CO USA. [Kay, Jonathan] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. EM habujudeh@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193; Kay, Jonathan/0000-0002-8970-4260 NR 41 TC 53 Z9 55 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2009 VL 253 IS 1 BP 81 EP 89 DI 10.1148/radiol.2531082160 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512UB UT WOS:000271275200012 PM 19709997 ER PT J AU Hess, DR Pang, JM Camargo, CA AF Hess, Dean R. Pang, Jessica M. Camargo, Carlos A., Jr. TI A Survey of the Use of Noninvasive Ventilation in Academic Emergency Departments in the United States SO RESPIRATORY CARE LA English DT Article DE asthma; chronic obstructive pulmonary disease; congestive heart failure; emergency medicine; noninvasive ventilation; respiratory care; survey ID ACUTE RESPIRATORY-FAILURE; POSITIVE-PRESSURE VENTILATION; MECHANICAL VENTILATION; TRIAL; MASK AB OBJECTIVE: To determine the frequency of, and barriers to, use of noninvasive ventilation (NIV) for adult patients with acute asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF) in academic emergency departments (EDs). METHODS: A survey instrument was developed by the authors, pilot tested, and distributed to one physician (MD) and one respiratory therapist (RT) at the 132 hospitals with emergency medicine residencies. RESULTS: The response rate was 90%. Ninety-nine percent of RTs and 64% of MDs are very familiar with NIV (P < .001). The reported time needed to initiate NIV was < 10 min for 41% of sites (< 20 min for 89%). Compared to the time requirement in other clinical areas, 60% of RTs reported that NIV "takes no additional time" in the ED. An RT is always present in 38% the EDs, and equipment for NIV is readily available in 76% of the EDs. The majority reported that NIV use is about right for acute COPD, CHF, and asthma. NIV is used infrequently for asthma (89% reported use in < 20% of these patients), while 66% reported use in > 20% of COPD patients and 67% reported use in > 20% of CHF patients (P < .001, as compared to asthma). The perceived utility of NIV was significantly different between the 3 diagnoses (P < .001); there was more uncertainty about the utility of NIV for asthma. Bilevel ventilators and oronasal masks are most commonly used for NIV. Nearly all of the centers administer bronchodilators in-line with NIV. CONCLUSIONS: Consistent with available evidence, NIV use is more common in the ED for acute COPD and CHF than for acute asthma. Barriers to greater use of NIV in the ED include physician familiarity, availability of RT and equipment in the ED, and time required for NIV. For acute asthma, uncertainty about therapeutic benefits remains a challenge. C1 [Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Resp Care Serv, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 25 TC 40 Z9 40 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD OCT PY 2009 VL 54 IS 10 BP 1306 EP 1312 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 509WZ UT WOS:000271051300004 PM 19796409 ER PT J AU Bierer, GB Hoo, GWS AF Bierer, Gregory B. Hoo, Guy W. Soo TI Noninvasive Ventilation for Acute Respiratory Failure: A National Survey of Veterans Affairs Hospitals SO RESPIRATORY CARE LA English DT Article DE noninvasive ventilation; respiratory failure; hypercapnia; respiratory therapists ID POSITIVE-PRESSURE VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; MECHANICAL VENTILATION; ACUTE EXACERBATIONS; CONTROLLED-TRIAL; CARE; EDEMA; COPD; METAANALYSIS; STANDARDS AB BACKGROUND: The utilization of noninvasive ventilation (NIV) in the Veterans Affairs health-care system is not well characterized. A survey of physicians and respiratory therapists was conducted to better understand its use. METHODS: Three hospitals in each of 21 Veterans Affairs networks were selected based on severity of patient mix, level of staffing and workload. A request was sent via e-mail to Veterans Affairs respiratory therapists and critical care physicians at these hospitals to complete a 41-question survey using an Internet-based survey site. RESULTS: A total of 192/882 (22%) responses were received from a survey of about half (63/128) of the Veterans Affairs intensive care units (ICUs). Previous experience and training in NIV was limited. NIV is reported to be widely available and applied in both monitored (ICU, step-down, emergency department) and unmonitored (ward) settings. NIV was identified as a first-line option for COPD and CHF, but perceived use was less. Sixty-four percent of respiratory therapists felt NIV was used < 50% of the time when indicated, compared to 29% of physicians (P < .001). Reported NIV use varied, with 45% treating 0-4 patients a month and 23% with > 10 patients a month. Larger ICUs reported more frequent use of NIV (> 10 patients a month) than smaller ICUs (P = .02). Written guidelines were noted by 65%, but only 27% had titration guidelines. The perceived efficacy of NIV was low, with a success rate of > 50% noted by only 29% of respondents. CONCLUSIONS: The perception of NIV use in the Veterans Affairs hospitals varies significantly. This survey revealed a wide range of training and experience, location of use, presence of written guidelines, and methods of delivery. Notable perceptual differences exist between respiratory therapists and physicians. Underutilization of NIV and low rates of perceived efficacy are major findings. C1 [Hoo, Guy W. Soo] W Los Angeles Vet Affairs Healthcare Ctr, Pulm & Crit Care Sect, Los Angeles, CA 90073 USA. [Bierer, Gregory B.] Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. [Hoo, Guy W. Soo] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Hoo, GWS (reprint author), W Los Angeles Vet Affairs Healthcare Ctr, Pulm & Crit Care Sect, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM guy.soohoo@va.gov NR 38 TC 23 Z9 24 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD OCT PY 2009 VL 54 IS 10 BP 1313 EP 1320 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 509WZ UT WOS:000271051300005 PM 19796410 ER PT J AU Adams, SG Anzueto, A Briggs, DD Leimer, I Kesten, S AF Adams, Sandra G. Anzueto, Antonio Briggs, Dick D., Jr. Leimer, Inge Kesten, Steven TI Evaluation of withdrawal of maintenance tiotropium in COPD SO RESPIRATORY MEDICINE LA English DT Article DE COPD; Tiotropium; Spirometry; Peak expiratory flow rate; St. George's Respiratory Questionnaire; Transition dyspnea index ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW; HEALTH OUTCOMES; DIAGNOSIS; DYSPNEA AB Introduction: In chronic diseases such as chronic obstructive pulmonary disease (COPD), patients may not perceive all of the benefits of drug therapy until withdrawal. Thus, we evaluated the effect of tiotropium withdrawal. on clinical variables. Methods: COPD subjects who participated in two identical 1-year, prospective, double-blind, placebo-controlled studies of tiotropium 18 mu g once daily who completed a 3-week visit following discontinuation of therapy were included in this analysis. Outcomes measured included dyspnea (transition dyspnea, index [TDI]), Peak Expiratory Flow Rate (PEFR), health status (St George's Respiratory Questionnaire [SGRQ]), and rescue beta(2)-agonist use. Results: Overall, the tiotropium group exhibited significant improvements in clinical. parameters at the end of therapy. Of the entire cohort of 921 patients, 713 patients (77%) completed 3-weeks post-withdrawal evaluation. Patients in the tiotropium group had 1.1 unit worsening in TDI, decreased in PEFR, health status and reduced beta(2)-agonist medication following treatment discontinuation, white the placebo group remained relatively stable. Conclusions: The withdrawal of tiotropium results in worsening of COPD over a three-week interval. There was no evidence of a rebound effect in response to tiotropium withdrawal. Published by Elsevier Ltd. C1 [Adams, Sandra G.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Adams, Sandra G.; Anzueto, Antonio] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Briggs, Dick D., Jr.] Univ Alabama, Birmingham, AL 35294 USA. [Leimer, Inge; Kesten, Steven] Boehringer Ingelheim Pharma GmbH & Co KG, D-55216 Ingelheim, Germany. RP Adams, SG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7400 Merton Minter Blvd 111E, San Antonio, TX 78229 USA. EM adamssg@uthscsa.edu FU Boehringer Ingetheim Pharmaceuticals, Inc FX Boehringer Ingetheim Pharmaceuticals, Inc. provided funding and support for the clinical trials including collaborating with investigators regarding the original study design and statistical analyses. The authors of this manuscript were not given any compensation for writing or participating in the development of this manuscript. NR 18 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD OCT PY 2009 VL 103 IS 10 BP 1415 EP 1420 DI 10.1016/j.rmed.2009.05.018 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 497IT UT WOS:000270053200004 PM 19523796 ER PT J AU Torrey, EF Buka, S Cannon, TD Goldstein, JM Seidman, LJ Liu, TL Hadley, T Rosso, IM Bearden, C Yolken, RH AF Torrey, E. Fuller Buka, Stephen Cannon, Tyrone D. Goldstein, Jill M. Seidman, Larry J. Liu, Tianli Hadley, Trevor Rosso, Isabelle M. Bearden, Carrie Yolken, Robert H. TI Paternal age as a risk factor for schizophrenia: How important is it? SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Paternal age; Schizophrenia; Risk factors ID PARENTAL AGE; METAANALYSIS; BIRTH; POPULATION; ASSOCIATION; PSYCHOSIS; CANCER AB Advanced paternal age has been widely cited as a risk factor for schizophrenia among offspring and even claimed to account for one-quarter of all cases. We carried out a new study on 25,025 offspring from the Collaborative Perinatal Project (CPP), including 168 diagnosed with psychosis and 88 with narrowly defined schizophrenia. We also conducted a meta-analysis of this and nine other studies for which comparable age-cohort data were available. The mean paternal age for the CPP cases was slightly, but not significantly, higher than the matched controls (p = 0.28). Meta-analyses including these new results were conducted to determine the relative risk associated with alternative definitions of advanced paternal age (35, 45 or 55 years and older). These yielded pooled odds ratios and 95% confidence intervals of 1.28 (1.10, 1.48), 1.38 (0.95, 2.01) and 2.22 (1.46, 3.37), respectively. Thus, increased paternal age appears to be a risk factor for schizophrenia primarily among offspring of fathers ages 55 and over. In these 10 studies, such fathers accounted for only 0.6% of all births. Compared with other known risk factors for schizophrenia, advanced paternal age appears to be intermediate in magnitude. Advanced paternal age is also known to be a risk factor for some chromosomal and neoplastic diseases in the offspring where the cause is thought to be chromosomal aberrations and mutations of the aging germline. Similar mechanisms may account for the relationship between advanced paternal age and schizophrenia risk. (C) 2009 Elsevier B.V. All rights reserved. C1 [Torrey, E. Fuller] Stanley Med Res Inst, Chevy Chase, MD 20815 USA. [Buka, Stephen; Liu, Tianli] Brown Univ, Dept Community Hlth, Providence, RI 02806 USA. [Cannon, Tyrone D.; Bearden, Carrie] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Cannon, Tyrone D.; Bearden, Carrie] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens Hlth,Dept Psychiat, Boston, MA 02120 USA. [Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens Hlth,Dept Med, Boston, MA 02120 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Dept Psychiat, Beth Israel Deaconess Med Ctr,Publ Psychiat Div, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Hadley, Trevor] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Rosso, Isabelle M.] McLean Hosp, Belmont, MA 02478 USA. [Rosso, Isabelle M.] Harvard Univ, Sch Med, Belmont, MA 02478 USA. [Yolken, Robert H.] Johns Hopkins Univ, Stanley Div Dev Neurovirol, Baltimore, MD 21287 USA. RP Torrey, EF (reprint author), Stanley Med Res Inst, 8401 Connecticut Ave,Suite 200, Chevy Chase, MD 20815 USA. EM torreyf@stanleyresearch.org; Stephen_Buka@brown.edu; cannon@psych.ucla.edu; jill_goldstein@hms.harvard.edu; lseidman@bidmc.harvard.edu; Tianli_Liu@brown.edu; thadley@mail.med.upenn.edu; irosso@hms.harvard.edu; cbearden@mednet.ucla.edu; yolken@mail.jhmi.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU Stanley Medical Research Institute (SMRI) FX All support for the study came from the Stanley Medical Research Institute (SMRI), a nonprofit research organization. NR 38 TC 36 Z9 36 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2009 VL 114 IS 1-3 BP 1 EP 5 DI 10.1016/j.schres.2009.06.017 PG 5 WC Psychiatry SC Psychiatry GA 506FE UT WOS:000270758700001 PM 19683417 ER PT J AU Wolf, K Alexander, S Schacht, V Coussens, LM von Andrian, UH van Rheenen, J Deryugina, E Friedl, P AF Wolf, Katarina Alexander, Stephanie Schacht, Vivien Coussens, Lisa M. von Andrian, Ulrich H. van Rheenen, Jacco Deryugina, Elena Friedl, Peter TI Collagen-based cell migration models in vitro and in vivo SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Cancer cell invasion models; Connective tissue geometry; Physical collagen spacing; Confocal reflection microscopy; Second harmonic generation microscopy ID TYPE-1 MATRIX-METALLOPROTEINASE; RABBIT EAR CHAMBER; EXTRACELLULAR-MATRIX; 2ND-HARMONIC GENERATION; MULTIPHOTON MICROSCOPY; MELANOMA-CELLS; PERICELLULAR PROTEOLYSIS; MECHANICAL-PROPERTIES; ADHESION MOLECULE-1; BASEMENT-MEMBRANE AB Fibrillar collagen is the most abundant extracellular matrix (ECM) constituent which maintains the structure of most interstitial tissues and organs, including skin, gut, and breast. Density and spatial alignments of the three-dimensional (3D) collagen architecture de. ne mechanical tissue properties, i.e. stiffness and porosity, which guide or oppose cell migration and positioning in different contexts, such as morphogenesis, regeneration, immune response, and cancer progression. To reproduce interstitial cell movement in vitro with high in vivo fidelity, 3D collagen lattices are being reconstituted from extracted collagen monomers, resulting in the re-assembly of a fibrillar meshwork of defined porosity and stiffness. With a focus on tumor invasion studies, we here evaluate different in vitro collagen-based cell invasion models, employing either pepsinized or non-pepsinized collagen extracts, and compare their structure to connective tissue in vivo, including mouse dermis and mammary gland, chick chorioallantoic membrane (CAM), and human dermis. Using confocal reflection and two-photon-excited second harmonic generation (SHG) microscopy, we here show that, depending on the collagen source, in vitro models yield homogeneous fibrillar texture with a quite narrow range of pore size variation, whereas all in vivo scaffolds comprise a range from low-to high-density fibrillar networks and heterogeneous pore sizes within the same tissue. Future in-depth comparison of structure and physical properties between 3D ECM-based models in vitro and in vivo are mandatory to better understand the mechanisms and limits of interstitial cell movements in distinct tissue environments. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Wolf, Katarina; Friedl, Peter] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, Dept Cell Biol, NL-6500 HB Nijmegen, Netherlands. [Alexander, Stephanie; Friedl, Peter] Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, D-97080 Wurzburg, Germany. [Schacht, Vivien] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. [Schacht, Vivien] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Coussens, Lisa M.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. [van Rheenen, Jacco] KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. [van Rheenen, Jacco] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. [Deryugina, Elena] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. RP Wolf, K (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Cell Biol 283, NCMLS, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM k.wolf@ncmls.ru.nl; stephanie.alexander@virchow.uni-wuerzburg.de; vivien.schacht@uniklinik-freiburg.de; Lisa.Coussens@ucsf.edu; uva@idi.harvard.edu; j.vanrheenen@hubrecht.eu; deryugin@scripps.edu; p.friedl@ncmls.ru.nl RI Wolf, Katarina/A-7787-2010; Friedl, Peter/A-8961-2010; Alexander, Stephanie/B-7150-2012; von Andrian, Ulrich/A-5775-2008; van Rheenen, Jacco/G-3655-2014; Wolf, K.A./L-4765-2015 OI Alexander, Stephanie/0000-0002-8308-3977; FU Deutsche Forschungsgemeinschaft [FR 1155/8-3]; Dutch Cancer Foundation [KWF 2008-4031]; NIH [CA098075]; BCRP [W81XWH-06-1-0416] FX We thank T. Mempel for the preparation of a mesenterium and a mouse cremaster muscle, I. Mazo and K. Engelke for the preparation of a mouse skull, and S. Tjabringa for the preparation of a human DED sample. For assistance and imaging with MP microscopy we thank H. Leung, M. Hirschberg, G. Bakker and M. van Dommelen. Further, we acknowledge IBFB Pharma GmbH, Leipzig for providing a calf collagen sample. This work was supported by the Deutsche Forschungsgemeinschaft (FR 1155/8-3) and the Dutch Cancer Foundation (KWF 2008-4031). LMC was supported from a grant from the NIH CA098075 and the BCRP W81XWH-06-1-0416. NR 69 TC 205 Z9 209 U1 10 U2 115 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD OCT PY 2009 VL 20 IS 8 BP 931 EP 941 DI 10.1016/j.semcdb.2009.08.005 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 552OA UT WOS:000274300800007 PM 19682592 ER PT J AU Jaglowski, SM Linden, E Termuhlen, AM Flynn, JM AF Jaglowski, Samantha M. Linden, Erica Termuhlen, Amanda M. Flynn, Joseph M. TI Lymphoma in Adolescents and Young Adults SO SEMINARS IN ONCOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; ACUTE-LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; CHILDRENS CANCER GROUP; PEDIATRIC-ONCOLOGY-GROUP; FRANKFURT-MUNSTER GROUP; EPSTEIN-BARR-VIRUS; HIGH-DOSE THERAPY; ADVANCED FOLLICULAR LYMPHOMA C1 [Jaglowski, Samantha M.; Flynn, Joseph M.] Ohio State Univ, Dept Hematol, Columbus, OH 43210 USA. [Jaglowski, Samantha M.; Flynn, Joseph M.] Ohio State Univ, Dept Oncol, Columbus, OH 43210 USA. [Linden, Erica] Dana Farber Canc Inst, Dept Hematol & Med Oncol, Boston, MA 02115 USA. [Termuhlen, Amanda M.] Ohio State Univ, Dept Pediat, Nationwide Childrens Hosp, Columbus, OH 43210 USA. RP Flynn, JM (reprint author), B302 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. RI Jaglowski, Samantha/E-3304-2011; OI Jaglowski, Samantha/0000-0002-4335-2554 FU Lance Armstrong Adolescent and Young Adult Project FX Supported by a Lance Armstrong Adolescent and Young Adult Project Grant NR 239 TC 25 Z9 29 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2009 VL 36 IS 5 BP 381 EP 418 DI 10.1053/j.seminoncol.2009.07.009 PG 38 WC Oncology SC Oncology GA 510KF UT WOS:000271086700004 PM 19835736 ER PT J AU Albritton, K Barr, R Bleyer, A AF Albritton, Karen Barr, Ronald Bleyer, Archie TI The Adolescence of Young Adult Oncology SO SEMINARS IN ONCOLOGY LA English DT Review ID COMPREHENSIVE GERIATRIC ASSESSMENT; ACUTE LYMPHOBLASTIC-LEUKEMIA; CANCER CLINICAL-TRIALS; HEALTH-CARE; FERTILITY PRESERVATION; TREATMENT ASSIGNMENT; PALLIATIVE CARE; OLDER PATIENTS; SERVICE NEEDS; TRANSITION C1 [Bleyer, Archie] St Charles Hosp, Bend, OR 97701 USA. [Albritton, Karen] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Barr, Ronald] McMaster Univ, Dept Pediat, Hamilton, ON, Canada. [Barr, Ronald] McMaster Univ, Dept Pathol, Hamilton, ON, Canada. [Barr, Ronald] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Bleyer, Archie] Oregon Hlth & Sci Univ, Dept Radiat Med, Portland, OR 97201 USA. RP Bleyer, A (reprint author), St Charles Hosp, 2500 NE Neff Rd, Bend, OR 97701 USA. FU Aflac Foundation FX Supported in part by the Aflac Foundation NR 56 TC 16 Z9 16 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2009 VL 36 IS 5 BP 478 EP 488 DI 10.1053/j.seminoncol.2009.07.007 PG 11 WC Oncology SC Oncology GA 510KF UT WOS:000271086700011 PM 19835743 ER PT J AU El-Din, MAA Taghian, AG AF El-Din, Mohamed A. Alm Taghian, Alphonse G. TI Breast Conservation Therapy for Patients With Locally Advanced Breast Cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article DE breast cancer; locally advanced; breast conservation ID POSTMASTECTOMY RADIATION IMPROVES; SURGICAL ADJUVANT BREAST; NEOADJUVANT CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; RANDOMIZED-TRIAL; PATHOLOGICAL RESPONSE; LYMPH-NODES; 3 CM; INDUCTION CHEMOTHERAPY; CHEMOENDOCRINE THERAPY C1 [El-Din, Mohamed A. Alm; Taghian, Alphonse G.] Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [El-Din, Mohamed A. Alm] Tanta Univ Hosp, Tanta Fac Med, Dept Radiat Oncol, Tanta, Egypt. RP Taghian, AG (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, 100 Blossom St,Cox Bldg 302, Boston, MA 02114 USA. EM ataghian@partners.org NR 55 TC 8 Z9 8 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2009 VL 19 IS 4 BP 229 EP 235 DI 10.1016/j.semradonc.2009.05.005 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 494MH UT WOS:000269817000006 ER PT J AU Vijayaraghavan, G Kurup, D Singh, A AF Vijayaraghavan, Gopal Kurup, Divya Singh, Ajay TI Imaging of Acute Abdomen and Pelvis: Common Acute Pathologies SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID SMALL-BOWEL OBSTRUCTION; ACUTE-PANCREATITIS; ACUTE APPENDICITIS; HELICAL CT; DIAGNOSIS; MANAGEMENT; SPECTRUM; PAIN; DIVERTICULITIS; COMPLICATIONS C1 [Kurup, Divya; Singh, Ajay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Vijayaraghavan, Gopal] Univ Massachusetts, Dept Radiol, Mem Hlth Ctr, Worcester, MA 01605 USA. RP Singh, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 10 Museum Way,524, Cambridge, MA 02141 USA. EM mghpartners@yahoo.com NR 35 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD OCT PY 2009 VL 44 IS 4 BP 221 EP 227 DI 10.1053/j.ro.2009.05.009 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 491WL UT WOS:000269612600004 PM 19715787 ER PT J AU Kaewlai, R Kurup, D Singh, A AF Kaewlai, Rathachai Kurup, Divya Singh, Ajay TI Imaging of Abdomen and Pelvis: Uncommon Acute Pathologies SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSM; ACUTE MESENTERIC ISCHEMIA; GASTROINTESTINAL-TRACT PERFORATION; SPONTANEOUS SPLENIC RUPTURE; HIGH-ATTENUATING CRESCENT; ADULT INTUSSUSCEPTION; CT FINDINGS; INTERNAL HERNIA; VASCULAR COMPROMISE; IMPENDING RUPTURE C1 [Kaewlai, Rathachai; Kurup, Divya; Singh, Ajay] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Singh, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 10 Museum Way,524, Cambridge, MA 02141 USA. EM mghpartners@yahoo.com OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 53 TC 1 Z9 1 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD OCT PY 2009 VL 44 IS 4 BP 228 EP 236 DI 10.1053/j.ro.2009.05.004 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 491WL UT WOS:000269612600005 PM 19715788 ER PT J AU Koh, I Josephson, L AF Koh, Isaac Josephson, Lee TI Magnetic Nanoparticle Sensors SO SENSORS LA English DT Review DE magnetic particles; magnetic nanoparticles; target molecules; biosensors; magnetization ID QUANTUM INTERFERENCE DEVICE; ANTIFERROMAGNETIC NANOPARTICLES; MOLECULAR-INTERACTIONS; RELAXATION; CANCER; BIOSENSOR; NANOSENSORS; NANOCRYSTALS; SENSITIVITY; RESONANCE AB Many types of biosensors employ magnetic nanoparticles (diameter = 5-300 nm) or magnetic particles (diameter = 300-5,000 nm) which have been surface functionalized to recognize specific molecular targets. Here we cover three types of biosensors that employ different biosensing principles, magnetic materials, and instrumentation. The first type consists of magnetic relaxation switch assay-sensors, which are based on the effects magnetic particles exert on water proton relaxation rates. The second type consists of magnetic particle relaxation sensors, which determine the relaxation of the magnetic moment within the magnetic particle. The third type is magnetoresistive sensors, which detect the presence of magnetic particles on the surface of electronic devices that are sensitive to changes in magnetic fields on their surface. Recent improvements in the design of magnetic nanoparticles (and magnetic particles), together with improvements in instrumentation, suggest that magnetic material-based biosensors may become widely used in the future. C1 [Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Nucl Med & Mol Imaging,Ctr Translat Nucl Med, Charlestown, MA 02129 USA. [Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Koh, Isaac] T2 Biosyst, Cambridge, MA 02141 USA. RP Josephson, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Nucl Med & Mol Imaging,Ctr Translat Nucl Med, 149 13th St, Charlestown, MA 02129 USA. EM ikoh@T2biosystems.com; josephso@helix.mgh.harvard.edu FU NIH [U54 CA119349, P50 CA08635] FX This work was supported in part by NIH grants U54 CA119349 and P50 CA08635. NR 52 TC 102 Z9 105 U1 6 U2 89 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1424-8220 J9 SENSORS-BASEL JI Sensors PD OCT PY 2009 VL 9 IS 10 BP 8130 EP 8145 DI 10.3390/s91008130 PG 16 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 512QT UT WOS:000271265800029 PM 22408498 ER PT J AU Cheung, AC Bredella, MA Al Khalaf, M Grasruck, M Leidecker, C Gupta, R AF Cheung, Arnold C. Bredella, Miriam A. Al Khalaf, Ma'moun Grasruck, Michael Leidecker, Christianne Gupta, Rajiv TI Reproducibility of trabecular structure analysis using flat-panel volume computed tomography SO SKELETAL RADIOLOGY LA English DT Article DE Flat-panel volume CT (fp-VCT); Trabecular bone structure; Reproducibility ID IN-VIVO ASSESSMENT; BONE-STRUCTURE; DISTAL RADIUS; OSTEOPOROSIS PREVENTION; ANOREXIA-NERVOSA; CT; ARCHITECTURE; CALCANEUS; FRACTURE; MRI AB To determine inter-scan, inter-reader and intra-reader variability of trabecular structure analysis using flat-panel volume computed tomography (fp-VCT) in cadaver knee specimens. Five explanted knee specimens were imaged at three different time points using fp-VCT. Four parameters that quantify trabecular bone structure of the proximal tibia were measured by two observers at two different time points. Bland-Altman analysis was used to compute the inter-scan, inter-observer and intra-observer variability. Inter-scan variability was low, with a mean difference of 0% and a standard deviation less than 8.4% for each of the four parameters. The inter-observer and intra-observer variability was less than 2.8% +/- 8.5%. Fp-VCT is a method for assessing trabecular structure parameters with low inter-scan, inter-reader and intra-reader variability. C1 [Cheung, Arnold C.; Bredella, Miriam A.; Al Khalaf, Ma'moun; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Grasruck, Michael; Leidecker, Christianne] Siemens Med Solut, Erlangen, Germany. RP Gupta, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB 273A, Boston, MA 02114 USA. EM RGUPTA1@partners.org NR 28 TC 10 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD OCT PY 2009 VL 38 IS 10 BP 1003 EP 1008 DI 10.1007/s00256-009-0707-9 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 488VN UT WOS:000269378500009 PM 19430779 ER PT J AU Shimada, M AF Shimada, Masako TI A Challenging Case of Severe Acute Hypertriglyceridemia-Induced Pancreatitis SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID MANAGEMENT C1 [Shimada, Masako] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02115 USA. [Shimada, Masako] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shimada, M (reprint author), 50 Blossom St, Boston, MA USA. EM shimada@helix.mgh.harvard.edu NR 8 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD OCT PY 2009 VL 102 IS 10 BP 999 EP 1000 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 504JI UT WOS:000270611900005 PM 19738534 ER PT J AU Ross, DS Litofsky, D Ain, KB Bigos, T Brierley, JD Cooper, DS Haugen, BR Jonklaas, J Ladenson, PW Magner, J Robbins, J Skarulis, MC Steward, DL Maxon, HR Sherman, SI AF Ross, Douglas S. Litofsky, Danielle Ain, Kenneth B. Bigos, Thomas Brierley, James D. Cooper, David S. Haugen, Bryan R. Jonklaas, Jacqueline Ladenson, Paul W. Magner, James Robbins, Jacob Skarulis, Monica C. Steward, David L. Maxon, Harry R. Sherman, Steven I. TI Recurrence After Treatment of Micropapillary Thyroid Cancer SO THYROID LA English DT Article ID LYMPH-NODE METASTASIS; PAPILLARY; CARCINOMA; MICROCARCINOMA; DISEASE; EXPERIENCE; MANAGEMENT; INSTITUTE AB Background: Despite very low mortality associated with micropapillary thyroid cancer, locoregional recurrence is common and controversy exists regarding optimal surgical treatment and the role of adjunctive radioiodine. Methods: The National Thyroid Cancer Treatment Cooperative Study Group Registry was analyzed for recurrences in patients with unifocal versus multifocalmicropapillary cancer, with or without nodal disease, depending upon the extent of surgery and the use of adjunctive radioiodine. Six hundred eleven patients considered disease-free after initial therapy were followed for 2572 person-years. Results: Thirty patients (6.2%) had recurrences detected at a mean 2.8 years after primary treatment. Recurrences did not differ between patients with unifocal and multifocal disease overall; however, among patients who received less than a near-total thyroidectomy (NTT), those with multifocal disease had more recurrences than those with unifocal disease (18% vs. 4%, p = 0.01). Patients with multifocal disease who had a total (T) or NTT trended toward fewer recurrences than those undergoing less than an NTT (6% vs. 18%, p = 0.058). In patients who did not receive radioiodine therapy, recurrence was more common in patients with multifocal disease versus unifocal disease (7% vs. 2%, p - 0.02). However, radioiodine did not reduce recurrences in patients with multifocal disease or patients with positive nodes. Patients with positive nodes had more recurrences than node-negative patients regardless of surgical extent or use of radioiodine. Conclusions: Patients with micropapillary multifocal disease have a reduced risk of recurrence after a T/NTT compared with less surgery. A randomized, controlled trial is necessary and feasible to determine if radioiodine ablation of thyroid remnants is advantageous in patients with intrathyroidal micropapillary cancer. C1 [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Litofsky, Danielle; Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ain, Kenneth B.] Univ Kentucky, Med Ctr, VA Med Ctr, Lexington, KY USA. [Bigos, Thomas] Maine Med Ctr, Portland, ME 04102 USA. [Brierley, James D.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Cooper, David S.; Ladenson, Paul W.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Haugen, Bryan R.] Univ Colorado Denver, Aurora, CO USA. [Haugen, Bryan R.] Hlth Sci Ctr, Aurora, CO USA. [Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Magner, James] Genzyme Corp, Cambridge, MA USA. [Robbins, Jacob; Skarulis, Monica C.] NIH, Bethesda, MD 20892 USA. [Steward, David L.; Maxon, Harry R.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dross@partners.org RI Jonklaas, Jacqueline/G-2807-2010; OI Jonklaas, Jacqueline/0000-0002-2238-2666; Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 NR 21 TC 82 Z9 88 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD OCT PY 2009 VL 19 IS 10 BP 1043 EP U3 DI 10.1089/thy.2008.0407 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 512VR UT WOS:000271279900004 PM 19772419 ER PT J AU Nucera, C Nehs, MA Mekel, M Zhang, XF Hodin, R Lawler, J Nose, V Parangi, S AF Nucera, Carmelo Nehs, Matthew A. Mekel, Michal Zhang, Xuefeng Hodin, Richard Lawler, Jack Nose, Vania Parangi, Sareh TI A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma SO THYROID LA English DT Article ID GROWTH-FACTOR RECEPTOR; ATHYMIC NUDE-MICE; TRANSCRIPTION FACTORS; CANCER PROGRESSION; TRANSGENIC MICE; DRUG-EVALUATION; CELL-LINES; INHIBITION; XENOGRAFTS; EXPRESSION AB Background: Orthotopic mouse models of human cancer represent an important in vivo tool for drug testing and validation. Most of the human thyroid carcinoma cell lines used in orthotopic or subcutaneous models are likely of melanoma and colon cancer. Here, we report and characterize a novel orthotopic model of human thyroid carcinoma using a unique thyroid cancer cell line. Methods: We used the cell line 8505c, originated from a thyroid tumor histologically characterized by anaplastic carcinoma cell features. We injected 8505c cells engineered using a green fluorescent protein-positive lentiviral vector orthotopically into the thyroid of severe combined immunodeficient mice. Results: Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins. Conclusions: Here we describe a novel orthotopic thyroid carcinoma model using 8505c cells. This model can prove to be a reliable and useful tool to investigate in vivo biological mechanisms determining thyroid cancer aggressiveness, and to test novel therapeutics for the treatment of refractory or advanced thyroid cancers. C1 [Nucera, Carmelo; Nehs, Matthew A.; Mekel, Michal; Hodin, Richard; Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thyroid Canc Res Lab,Unit Endocrine Surg, Boston, MA 02115 USA. [Zhang, Xuefeng; Lawler, Jack] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Canc Biol & Angiogenesis,Dept Pathol, Boston, MA 02115 USA. [Nose, Vania] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thyroid Canc Res Lab,Unit Endocrine Surg, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org FU Experimental Endocrinology and Metabolic Diseases (Italy); National Institutes of Health; American College of Surgeons; American Thyroid Association FX Carmelo Nucera is recipient of a doctorate fellowship, Ph.D. program in Experimental Endocrinology and Metabolic Diseases (Italy). Sareh Parangi is funded through the National Institutes of Health, the American College of Surgeons, and the American Thyroid Association. We thank Dr. Yutaka Kawakami (Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan) for kindly providing the plasmid vector HIV-U6-GL3B-GFP. We also thank the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, for the laboratory support given to Vania Nose for the histological and immunohistochemical investigations. NR 38 TC 39 Z9 40 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD OCT PY 2009 VL 19 IS 10 BP 1077 EP 1084 DI 10.1089/thy.2009.0055 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 512VR UT WOS:000271279900009 PM 19772429 ER PT J AU Davis, JA Horn, DL Marr, KA Fishman, JA AF Davis, J. A. Horn, D. L. Marr, K. A. Fishman, J. A. TI Central nervous system involvement in cryptococcal infection in individuals after solid organ transplantation or with AIDS SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE Cryptococcus neoformans; cryptococcal infection; solid organ transplantation; AIDS; central nervous system ID HUMAN-IMMUNODEFICIENCY-VIRUS; CALCINEURIN-INHIBITOR AGENTS; NEOFORMANS INFECTION; ACTIVE SURVEILLANCE; RECIPIENTS; EPIDEMIOLOGY; MENINGITIS; MANAGEMENT; VIRULENCE; THERAPY AB Background Cryptococcus neoformans is an important pathogen of immunocompromised hosts. Manifestations of cryptococcal infection have not been compared between populations based on the nature of the underlying immune deficiencies. Methods The Prospective Antifungal Therapy Alliance (PATH) is a registry that collects clinical data from patients with invasive fungal infections from medical centers in North America. Univariate analyses and group comparisons were conducted from the PATH registry for cases of infection due to Cryptococcus species occurring between March 2004 and April 2008. Results A total 235 cases of proven infection due to Cryptococcus species were documented, all of which were due to C. neoformans (52 in solid organ transplant [SOT] recipients, 107 in patients infected with the human immunodeficiency virus [HIV], and 76 with neither HIV nor organ transplantation). A total of 140 cases manifested as meningitis (25 in SOT recipients, 88 in HIV-positive patients, and 27 in those with neither risk factor). Of individuals with cryptococcal infection, 44.2% of SOT recipients had central nervous system (CNS) disease, while 84.1% of those with HIV infection presented with CNS involvement (P=0.0265). SOT recipients receiving calcineurin inhibitors (CNIs) were less likely to have CNS involvement in cryptococcal infection (40.1% versus 66.7%). Overall, 12-week mortality for patients with cryptococcal infection in the PATH Alliance registry was 22.6% (21.2% for SOT, 15.9% for HIV-infected patients, and 32.9% for patients with risk factors other than HIV infection or organ transplantation). Conclusions In a prospectively assembled cohort of individuals with proven infection due to C. neoformans, CNS involvement was more common in individuals with HIV infection than in SOT recipients. The role of CNIs in the reduction of risk for CNS cryptococcosis remains to be defined. Overall survival of patients with cryptococcal infection in immunocompromised hosts has improved over time. Observed differences in the context of various host immune deficits provide a basis for further investigation of cryptococcosis and other opportunistic infections. C1 [Davis, J. A.; Fishman, J. A.] Massachusetts Gen Hosp, Transplant Infect Dis Program, Div Infect Dis, Boston, MA 02114 USA. [Davis, J. A.; Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA USA. [Horn, D. L.] Thomas Jefferson Univ Hosp, Div Infect Dis, Philadelphia, PA 19107 USA. [Marr, K. A.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis Program, Div Infect Dis, 55 Fruit St,GRJ504, Boston, MA 02114 USA. EM jfishman@partners.org FU Astellas Pharma US Inc. (APUS) FX We would like to acknowledge Astellas Pharma US Inc. (APUS) for their generous support, Axiom Real-Time Metrics Inc. (Axiom) for their expertise in registry management, and the many dedicated coordinators at each site. As the financial sponsor of the PATH Alliance, APUS observed, but did not influence, the design of the PATH Alliance registry by the independent Scientific Advisory Board. APUS contracts Axiom to provide overall management services for the PATH Alliance registry, comprising data management, site support, application and database hosting, administrative management, and data extraction and analysis. APUS also sponsored Axiom's services for this individual research project; these services were composed of data extraction, facilitation of statistical analyses, preparation of figures, and manuscript review. Disclosures: From the antifungal manufacturers, D.L.H. has received recent research funding from Astellas, has served as a consultant or advisor to Astellas and Pfizer, and has been a member of the speaker's bureau for Pfizer and Astellas. In addition, D.L.H. has received speaking honoraria from Roche. J.A.F. has received educational/research grant support from Astellas, consulting fees from Merck Inc., Biogen-IDEC, Hoffman LaRoche, Astellas, and Primera, and has been a member of the speaker's bureau for Astellas and Roche. K.A.M. has been a consultant or a member of advisory boards for Astellas, Merck, Pfizer, and Schering Plough. NR 21 TC 21 Z9 22 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD OCT PY 2009 VL 11 IS 5 BP 432 EP 437 DI 10.1111/j.1399-3062.2009.00424.x PG 6 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 502BS UT WOS:000270429700007 PM 19638005 ER PT J AU Henrich, TJ Marty, FM Milner, DA Thorner, AR AF Henrich, T. J. Marty, F. M. Milner, D. A., Jr. Thorner, A. R. TI Disseminated Geotrichum candidum infection in a patient with relapsed acute myelogenous leukemia following allogeneic stem cell transplantation and review of the literature SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE Geotrichum candidum; Galactomyces geotrichum; leukemia; stem cell transplantation; fungal infection; antifungal therapy ID AMPHOTERICIN-B; SUSCEPTIBILITY; ITRACONAZOLE; VORICONAZOLE; SEPTICEMIA; YEASTS AB P>We describe a woman with relapsed acute myelogenous leukemia after allogeneic stem cell transplantation who developed disseminated Geotrichum candidum infection during chemotherapy-induced neutropenia. The isolate was susceptible to voriconazole, amphotericin B, and micafungin in vitro. We review the literature regarding invasive infections with G. candidum, which predominantly affect immunocompromised hosts, and discuss potential therapies for this rare pathogen. C1 [Henrich, T. J.; Marty, F. M.; Thorner, A. R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Henrich, T. J.; Marty, F. M.; Milner, D. A., Jr.; Thorner, A. R.] Harvard Univ, Sch Med, Boston, MA USA. [Marty, F. M.; Thorner, A. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Milner, D. A., Jr.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Henrich, TJ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. EM thenrich@partners.org NR 18 TC 19 Z9 20 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD OCT PY 2009 VL 11 IS 5 BP 458 EP 462 DI 10.1111/j.1399-3062.2009.00418.x PG 5 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 502BS UT WOS:000270429700012 PM 19804480 ER PT J AU Pillai, S Cariappa, A Pirnie, SP AF Pillai, Shiv Cariappa, Annaiah Pirnie, Stephan P. TI Esterases and autoimmunity: the sialic acid acetylesterase pathway and the regulation of peripheral B cell tolerance SO TRENDS IN IMMUNOLOGY LA English DT Review ID ADHESION MOLECULE CD22-BETA; INDEPENDENT RESPONSES; CD22-DEFICIENT MICE; NEGATIVE REGULATOR; ANTIGEN RECEPTOR; NATURAL LIGANDS; DEFICIENT MICE; IMMUNE-SYSTEM; CD22; SELF AB The best studied mechanisms of B cell tolerance are receptor editing, clonal deletion and anergy. All of these mechanisms of B cell tolerance depend on the induction of signaling downstream of the B cell receptor by self-antigens. Another important and distinct mechanism of B cell tolerance involves the repression of antigen receptor signaling rather than its induction, utilizes the Lyn Src-family kinase, the SHP-1 tyrosine phosphatase, inhibitory members of the Siglec family, and a carbohydrate-modifying enzyme that is capable of negatively regulating B cell receptor activation known as sialic acid acetylesterase. C1 [Pillai, Shiv; Cariappa, Annaiah; Pirnie, Stephan P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU Alliance for Lupus Research; NIH [AI 064930, AI 076505] FX This work was supported by grants to SP from the Alliance for Lupus Research and the NIH (AI 064930 and AI 076505). NR 45 TC 30 Z9 31 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD OCT PY 2009 VL 30 IS 10 BP 488 EP 493 DI 10.1016/j.it.2009.07.006 PG 6 WC Immunology SC Immunology GA 511NB UT WOS:000271171100005 PM 19766537 ER PT J AU Kennelly, MJ Lemack, GE Foote, JE Trop, CS AF Kennelly, Michael J. Lemack, Gary E. Foote, Jenelle E. Trop, Cynthia S. TI Efficacy and Safety of Oxybutynin Transdermal System in Spinal Cord Injury Patients With Neurogenic Detrusor Overactivity and Incontinence: An Open-label, Dose-titration Study SO UROLOGY LA English DT Article ID MIXED URINARY-INCONTINENCE; DOUBLE-BLIND; BLADDER; URGE; PHARMACOKINETICS; TOLTERODINE; MULTICENTER; BEHAVIOR; CHLORIDE AB OBJECTIVES To evaluate the efficacy and safety of oxybutynin transdermal system (oxybutynin-TDS) in spinal cord injury patients with neurogenic detrusor overactivity and incontinence despite use of clean intermittent catheterization (CIC). METHODS This multicenter, open-label, dose-titration study included patients >= 18 years old. During an 8-week dose-titration period, oxybutynin-TDS doses were adjusted every 2 weeks, depending on symptoms. The primary efficacy end point was a change in daily number of CIC periods without leakage, from baseline to 8 weeks or last observation. Outcome parameters included 3-day voiding diary, CIC volume, and urodynamic parameters. Changes from baseline were analyzed with paired t tests. RESULTS Of 24 study participants (mean age, 41.9 years), 18 (75.0%) completed the study. Final oxybutynin-TDS doses were 7.8, 9.1, and 11.7 mg/d for 4, 9, and I I patients, respectively. Daily number of CIC periods without leakage increased significantly (mean change, 1.5 +/- 2.2; P = .0036) from baseline (2-4 +/- 1.8) to 8 weeks (3.9 +/- 1.9). CIC volume (P = .0029), reflex volume (P = .0466), maximal cystometric bladder capacity (P = .0009), and residual urine volume (P = .0023) all increased significantly, whereas detrusor pressure at maximal bladder capacity decreased significantly (P = .0457). The most common adverse events were application site reaction (12.5% of patients), dry mouth (8.3%), and abnormal vision (8.3%). No patient discontinued treatment because of an adverse event. CONCLUSIONS Oxybutynin-TDS was efficacious in spinal cord injury patients with neurogenic detrusor overactivity and was well tolerated at up to 3 times the standard dose. UROLOGY 74: 741-745, 2009. (C) 2009 Elsevier Inc. C1 [Kennelly, Michael J.] Carolinas Healthcare Syst, Carolinas Rehabil, Charlotte, NC 28203 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. James J Peters VA Med Ctr, Bronx, NY USA. Midtown Urol & Shepherd Ctr, Atlanta, GA USA. RP Kennelly, MJ (reprint author), Carolinas Healthcare Syst, Carolinas Rehabil, 1100 Blythe Blvd, Charlotte, NC 28203 USA. EM mkennelly@carolinas.org FU Watson Laboratories, Inc, Morristown, New Jersey FX This study was supported by Watson Laboratories, Inc, Morristown, New Jersey. Editorial assistance was provided by Scientific Cannexions, Newtown, Pennsylvania. Relevant financial disclosures and conflicts of interest: NR 25 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2009 VL 74 IS 4 BP 741 EP 745 DI 10.1016/j.urology.2009.05.008 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 506TA UT WOS:000270797900008 PM 19628264 ER PT J AU Cella, D Michaelson, MD Bushmakin, AG Cappelleri, JC Charbonneau, C Kim, ST Li, JZ Motzer, RJ AF Cella, D. Michaelson, M. D. Bushmakin, A. G. Cappelleri, J. C. Charbonneau, C. Kim, S. T. Li, J. Z. Motzer, R. J. TI FINAL QUALITY OF LIFE (QOL) RESULTS WITH GEOGRAPHICAL ANALYSIS FOR SUNITINIB VERSUS INTERFERON-ALFA, AS FIRST-LINE THERAPY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA (MRCC) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Cella, D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bushmakin, A. G.; Cappelleri, J. C.] Pfizer Oncol, New London, CT USA. [Charbonneau, C.] Pfizer Oncol, New York, NY USA. [Kim, S. T.; Li, J. Z.] Pfizer Oncol, La Jolla, CA USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD OCT PY 2009 VL 12 IS 7 BP A283 EP A283 DI 10.1016/S1098-3015(10)74389-8 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 495GH UT WOS:000269878100314 ER PT J AU de Moor, J Emmons, K de Moor, C AF de Moor, J. Emmons, K. de Moor, C. TI PATTERNS OF EMPLOYMENT AFTER CANCER: RESULTS OF A LONGITUDINAL STUDY SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [de Moor, J.] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Emmons, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [de Moor, C.] PPD Inc, Morrisville, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD OCT PY 2009 VL 12 IS 7 BP A284 EP A284 DI 10.1016/S1098-3015(10)74394-1 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 495GH UT WOS:000269878100319 ER PT J AU Johnson, M Desai, R Morgan, R Ashton, CM Deswal, A Chen, H Aparasu, R AF Johnson, M. Desai, R. Morgan, R. Ashton, C. M. Deswal, A. Chen, H. Aparasu, R. TI A MARGINAL STRUCTURAL MODEL TO COMPARE THE EFFECTIVENESS OF INDIVIDUAL ANGIOTENSIN RECEPTOR BLOCKERS IN VETERANS WITH CHRONIC HEART FAILURE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Johnson, M.; Desai, R.; Chen, H.; Aparasu, R.] Univ Houston, Houston, TX USA. [Morgan, R.] Univ Texas Houston, Houston, TX USA. [Ashton, C. M.] Methodist Inst Technol Innovat & Educ, Houston, TX USA. [Deswal, A.] Baylor Coll Med, Houston, TX 77030 USA. [Deswal, A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD OCT PY 2009 VL 12 IS 7 BP A313 EP A313 DI 10.1016/S1098-3015(10)74537-X PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 495GH UT WOS:000269878100462 ER PT J AU Meunier, J Regnault, A Robinson, D Rosa, K Miguel, JFS van de Velde, H Richardson, PG Cakana, A Dhawan, R AF Meunier, J. Regnault, A. Robinson, D. Rosa, K. San Miguel, J. F. van de Velde, H. Richardson, P. G. Cakana, A. Dhawan, R. TI IMPACT OF TUMOR RESPONSE ON HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS TREATED WITH VELCADE/MELPHALAN/PREDNISONE (V-MP): RESULTS FROM THE VISTA TRIAL SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Meunier, J.; Regnault, A.] Mapi Values France, Lyon, France. [Robinson, D.] Johnson & Johnson Pharmaceut Serv, Malvern, PA USA. [Rosa, K.] Mapi Values, Boston, MA USA. [San Miguel, J. F.] Hosp Univ Salamanca, Salamanca, Spain. [van de Velde, H.; Cakana, A.] Johnson & Johnson Pharmaceut R&D, Beerse, Belgium. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dhawan, R.] Johnson & Johnson Pharmaceut Serv LLC, Raritan, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD OCT PY 2009 VL 12 IS 7 BP A284 EP A284 DI 10.1016/S1098-3015(10)74390-4 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 495GH UT WOS:000269878100315 ER PT J AU Ramsey, SD McDermott, CL Zeliadt, SB Blough, DK Fedorenko, CR Arora, NK Penson, DF Oakley-Girvan, I Hamilton, AS Van den Eeden, SK Potosky, AL AF Ramsey, S. D. McDermott, C. L. Zeliadt, S. B. Blough, D. K. Fedorenko, C. R. Arora, N. K. Penson, D. F. Oakley-Girvan, I Hamilton, A. S. Van den Eeden, S. K. Potosky, A. L. TI COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM) USE AMONG LOCAL STAGE PROSTATE CANCER PATIENTS: TYPES, FACTORS ASSOCIATED WITH USE AND PERCEIVED BENEFITS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Ramsey, S. D.; McDermott, C. L.; Fedorenko, C. R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Zeliadt, S. B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Blough, D. K.] Univ Washington, Seattle, WA 98195 USA. [Arora, N. K.] NCI, Bethesda, MD 20892 USA. [Penson, D. F.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. [Oakley-Girvan, I] No Calif Canc Ctr, Fremont, CA USA. [Hamilton, A. S.] USC, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA USA. [Van den Eeden, S. K.] Kaiser Permanente, Oakland, CA USA. [Potosky, A. L.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD OCT PY 2009 VL 12 IS 7 BP A283 EP A283 DI 10.1016/S1098-3015(10)74386-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 495GH UT WOS:000269878100311 ER PT J AU Stone, DH Conrad, MF Albadawi, H Entabi, F Stoner, MC Cambria, RP Watkins, MT AF Stone, David H. Conrad, Mark F. Albadawi, Hassan Entabi, Fateh Stoner, Michael C. Cambria, Richard P. Watkins, Michael T. TI Effect of PJ34 on Spinal Cord Tissue Viability and Gene Expression in a Murine Model of Thoracic Aortic Reperfusion Injury SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE paralysis; ischemia; reperfusion injury; poly ADP-ribose polymerase; inflammation ID ACUTE-RENAL-FAILURE; THORACOABDOMINAL ANEURYSM REPAIR; PREDICTIVE FACTORS; CEREBRAL-ISCHEMIA; POTENT INHIBITOR; RISK-FACTOR; SURGERY; SYNTHETASE; REPLACEMENT; DYSFUNCTION AB Introduction: These studies were designed to determine whether PJ34, a novel Poly-ADP Ribose Polymerase Inhibitor, modulates expression of markers of stress and inflammation in the spinal cord following ischemia/reperfusion(TAR). Methods: 129S1/SvImj mice were subjected to thoracic aortic occlusion and 48 hours of reperfusion (n = 38). Experimental Groups included: Untreated Control (UC, n = 21); PJ34 (PJ34, n = 11) and sham (S, n = 6). At 48 hours, mice were euthanized for mRNA analysis and assessment of spinal cord viability. Results: PJ34 improved spinal cord tissue viability following TAR (UC:53.1 +/- 6.3, PJ34:73.5 +/- 4.1% sham, p < 0.01). mRNA analysis revealed significant expression of stress response genes in UC and PJ34 treated mice. Conclusions: PJ34 enhanced mitochondrial activity and preserved neurologic function following TAR despite the expression of stress and pro-inflammatory markers within the spinal cord. The ongoing cord stress response in neurologically intact PJ34 treated mice may indicate the potential to develop delayed neurologic dysfunction. C1 [Stone, David H.; Conrad, Mark F.; Albadawi, Hassan; Entabi, Fateh; Stoner, Michael C.; Cambria, Richard P.; Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg,Sch Med, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg,Sch Med, 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM mtwatkins@partners.org FU EVEREST Foundation; Pacific Vascular Research Foundation; Department of Surgery; Division of Vascular and Endovascular Surgery, Massachusetts General Hospital FX This work is supported by funding from the EVEREST Foundation, the Pacific Vascular Research Foundation, the Department of Surgery, and Division of Vascular and Endovascular Surgery, Massachusetts General Hospital. NR 39 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD OCT PY 2009 VL 43 IS 5 BP 444 EP 451 DI 10.1177/1538574409333582 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 510JQ UT WOS:000271084900003 PM 19640911 ER PT J AU Abularrage, CJ Crawford, RS Patel, VI Conrad, MF AF Abularrage, Christopher J. Crawford, Robert S. Patel, Virendra I. Conrad, Mark F. TI Diagnostic Strategies for the Persistent Sciatic Artery SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE sciatic; artery; persistent; diagnosis; management ID CLINICAL ASPECTS; ANGIOGRAPHY; MANAGEMENT; ANEURYSM AB Persistent sciatic artery (PSA) is a rare congenital vascular anomaly that leads to aneurysmal degeneration and atherosclerotic changes. A careful understanding of the embryology is mandatory as variations in vascular development determine the optimal treatment. We present a case of an 85-year-old female who was incidentally found to have a PSA aneurysm, and review the literature. C1 [Abularrage, Christopher J.; Crawford, Robert S.; Patel, Virendra I.; Conrad, Mark F.] Harvard Univ, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Sch Med, Boston, MA 02114 USA. RP Abularrage, CJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Sch Med, 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM cabularrage@partners.org NR 19 TC 4 Z9 4 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD OCT PY 2009 VL 43 IS 5 BP 485 EP 489 DI 10.1177/1538574409339359 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 510JQ UT WOS:000271084900010 PM 19640921 ER PT J AU Molyneaux, BJ Arlotta, P Fame, RM MacDonald, JL MacQuarrie, KL Macklis, JD AF Molyneaux, Bradley J. Arlotta, Paola Fame, Ryann M. MacDonald, Jessica L. MacQuarrie, Kyle L. Macklis, Jeffrey D. TI Novel Subtype-Specific Genes Identify Distinct Subpopulations of Callosal Projection Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CORTICOSPINAL MOTOR-NEURONS; CEREBRAL-CORTEX; SUBVENTRICULAR ZONE; PYRAMIDAL NEURONS; CORTICOSTRIATAL NEURONS; DEVELOPING NEOCORTEX; AXONAL PROJECTIONS; LAYER NEURONS; EXPRESSION; MOUSE AB Little is known about the molecular development and heterogeneity of callosal projection neurons (CPN), cortical commissural neurons that connect homotopic regions of the two cerebral hemispheres via the corpus callosum and that are critical for bilateral integration of cortical information. Here we report on the identification of a series of genes that individually and in combination define CPN and novel CPN subpopulations during embryonic and postnatal development. We used in situ hybridization analysis, immunocytochemistry, and retrograde labeling to define the layer-specific and neuron-type-specific distribution of these newly identified CPN genes across different stages of maturation. We demonstrate that a subset of these genes (e.g., Hspb3 and Lpl) appear specific to all CPN (in layers II/III and V-VI), whereas others (e.g., Nectin-3, Plexin-D1, and Dkk3) discriminate between CPN of the deep layers and those of the upper layers. Furthermore, the data show that several genes finely subdivide CPN within individual layers and appear to label CPN subpopulations that have not been described previously using anatomical or morphological criteria. The genes identified here likely reflect the existence of distinct programs of gene expression governing the development, maturation, and function of the newly identified subpopulations of CPN. Together, these data define the first set of genes that identify and molecularly subcategorize distinct populations of callosal projection neurons, often located in distinct subdivisions of the canonical cortical laminae. C1 [Macklis, Jeffrey D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nervous Syst Repair,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nayef Al Rodhan Labs,Program Neurosci, Boston, MA 02114 USA. Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nervous Syst Repair,Dept Neurosurg, Edwards Res Bldg,EDR 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu OI Molyneaux, Bradley/0000-0002-3377-1229; MacDonald, Jessica/0000-0002-9111-5756 FU National Institutes of Health [NS41590, NS45523, NS49553]; Harvard Stem Cell Institute; Claflin Distinguished Scholar Award; ALS Association; Harvard Medical Science Training Program; United Sydney Association FX This work was partially supported by National Institutes of Health Grants NS41590 and NS45523 and the Harvard Stem Cell Institute (J.D.M.), with additional infrastructure support by National Institutes of Health Grant NS49553. P.A. was supported by a Claflin Distinguished Scholar Award, the Harvard Stem Cell Institute, and the ALS Association. B. J.M. was supported by the Harvard Medical Science Training Program and the United Sydney Association. We thank A. Meleski and K. Quinn for technical assistance, and J. Menezes and members of the Macklis laboratory for suggestions and critical reading of this manuscript. NR 57 TC 95 Z9 96 U1 0 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 30 PY 2009 VL 29 IS 39 BP 12343 EP 12354 DI 10.1523/JNEUROSCI.6108-08.2009 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 501EV UT WOS:000270363300034 PM 19793993 ER PT J AU Leuchter, AF Cook, IA Marangell, LB Gilmer, WS Burgoyne, KS Howland, RH Trivedi, MH Zisook, S Jain, R McCracken, JT Fava, M Iosifescu, D Greenwald, S AF Leuchter, Andrew F. Cook, Ian A. Marangell, Lauren B. Gilmer, William S. Burgoyne, Karl S. Howland, Robert H. Trivedi, Madhukar H. Zisook, Sidney Jain, Rakesh McCracken, James T. Fava, Maurizio Iosifescu, Dan Greenwald, Scott TI Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study SO PSYCHIATRY RESEARCH LA English DT Article DE Major depression; Escitalopram; Predictors of treatment response; Genetic polymorphisms; Quantitative electroencephalography; Antidepressant Treatment Response (ATR) index ID SEROTONIN REUPTAKE INHIBITORS; NATIONAL-COMORBIDITY-SURVEY; STAR-ASTERISK-D; ANTIDEPRESSANT RESPONSE; PSYCHIATRIC-DISORDERS; UNITED-STATES; PRIMARY-CARE; EEG; METAANALYSIS; TRANSPORTER AB Patients with Major Depressive Disorder (MDD) may not respond to antidepressants for 8 weeks or longer. A biomarker that predicted treatment effectiveness after only 1 week could be clinically useful. We examined a frontal quantitative electroencephalographic (QEEG) biomarker, the Antidepressant Treatment Response (ATR) index, as a predictor of response to escitalopram, and compared ATR with other putative predictors. Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study. After 1 week of treatment with escitalopram, 10 mg, a second QEEG was performed, and the ATR was calculated. Subjects then were randomly assigned to continue with escitalopram, 10 mg, or change to alternative treatments. Seventy-three evaluable subjects received escitalopram for a total of 49 days. Response and remission rates were 52.1% and 38.4%, respectively. The ATR predicted both response and remission With 74% accuracy. Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors. Responders had larger decreases in Hamilton Depression Rating Scale (Ham-D(17)) scores at day 7 (P=0.005), but remitters did not. Clinician prediction based upon global impression of improvement at day 7 did not predict outcome. Logistic regression showed that the ATR and early Ham-D(17) changes were additive predictors of response, but the ATR was the only significant predictor of remission. Future studies should replicate these results prior to clinical use. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Leuchter, Andrew F.] Univ Calif Los Angeles, Lab Brain Behav & Pharmacol, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci,David Geffen Sch Med, Los Angeles, CA 90024 USA. [Marangell, Lauren B.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Gilmer, William S.] Northwestern Univ, Dept Psychiat, Chicago, IL 60611 USA. [Burgoyne, Karl S.] Harbor UCLA Med Ctr, Dept Psychiat, Los Angeles, CA USA. [Howland, Robert H.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Zisook, Sidney] UCSD, Dept Psychiat, San Diego, CA USA. [Jain, Rakesh] RD Clin Res, Houston, TX USA. [Fava, Maurizio; Iosifescu, Dan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greenwald, Scott] Aspect Med Syst, Norwood, MA USA. RP Leuchter, AF (reprint author), Univ Calif Los Angeles, Lab Brain Behav & Pharmacol, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci,David Geffen Sch Med, 760 Westwood Plaza,Rm 37-452, Los Angeles, CA 90024 USA. EM afl@ucla.edu RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 NR 39 TC 80 Z9 81 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD SEP 30 PY 2009 VL 169 IS 2 BP 124 EP 131 DI 10.1016/j.psychres.2009.06.004 PG 8 WC Psychiatry SC Psychiatry GA 503LP UT WOS:000270536100007 PM 19712979 ER PT J AU Leuchter, AF Cook, IA Gilmer, WS Marangell, LB Burgoyne, KS Howland, RH Trivedi, MH Zisook, S Jain, R Fava, M Iosifescu, D Greenwald, S AF Leuchter, Andrew F. Cook, Ian A. Gilmer, William S. Marangell, Lauren B. Burgoyne, Karl S. Howland, Robert H. Trivedi, Madhukar H. Zisook, Sidney Jain, Rakesh Fava, Maurizio Iosifescu, Dan Greenwald, Scott TI Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Major depression; Escitalopram; Bupropion; Differential medication response; Quantitative electroencephalography; Antidepressant treatment response (ATR) index ID SEROTONIN REUPTAKE INHIBITORS; STAR-ASTERISK-D; ANTIDEPRESSANT; SR; COMBINATION; SERTRALINE; INVENTORY; FAILURE; SSRIS; TREAT AB We examined the Antidepressant Treatment Response (ATR) index as a predictor of differential response and remission to escitalopram, bupropion, or a combination of the two medications, in subjects with major depressive disorder (MDD). Three hundred seventy-five subjects had a baseline quantitative electroencephalographic (QEEG) study preceding 1 week of treatment with escitalopram, 10 mg, after which a second QEEG was performed and the ATR index was calculated. Subjects then were randomized to continue escitalopram, switch to bupropion, or receive a combination of the two. Clinical response was assessed using the 17-item Hamilton Depression Rating Scale at 49 days of treatment. Accuracy of ATR in predicting response and remission was calculated. There were no significant differences between response and remission rates in the three treatment groups. A single ATR threshold was useful for predicting differential response to either escitalopram or bupropion monotherapy. Subjects with ATR values above the threshold were more than 2.4 times as likely to respond to escitalopram as those with low ATR values (68% vs. 28%). Subjects with ATR values below the threshold who were switched to bupropion treatment were 1.9 times as likely to respond to bupropion alone as those who remained on escitalopram treatment (53% vs. 28%). The ATR index did not provide a useful prediction of response to combination treatment. The ATR index may prove useful in predicting responsiveness to different antidepressant medications. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Leuchter, Andrew F.] Univ Calif Los Angeles, Lab Brain Behav & Pharmacol, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci,David Geffen Sch Med, Los Angeles, CA 90024 USA. [Gilmer, William S.] Northwestern Univ, Dept Psychiat, Feinberg Sch Med, Chicago, IL 60611 USA. [Marangell, Lauren B.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Burgoyne, Karl S.] Harbor UCLA Med Ctr, Dept Psychiat, Los Angeles, CA USA. [Howland, Robert H.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Zisook, Sidney] UCSD, Dept Psychiat, San Diego, CA USA. [Jain, Rakesh] RD Clin Res, Houston, TX USA. [Fava, Maurizio; Iosifescu, Dan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greenwald, Scott] Aspect Med Syst, Norwood, MA USA. RP Leuchter, AF (reprint author), Univ Calif Los Angeles, Lab Brain Behav & Pharmacol, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci,David Geffen Sch Med, 760 Westwood Plaza,Rm 37-452, Los Angeles, CA 90024 USA. EM afl@ucla.edu RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 NR 24 TC 59 Z9 61 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD SEP 30 PY 2009 VL 169 IS 2 BP 132 EP 138 DI 10.1016/j.psychres.2009.04.004 PG 7 WC Psychiatry SC Psychiatry GA 503LP UT WOS:000270536100008 PM 19709754 ER PT J AU Rajicic, N Finkelstein, DM Schoenfeld, DA AF Rajicic, Natasa Finkelstein, Dianne M. Schoenfeld, David A. CA Inflammation Host Response Injury TI Analysis of the relationship between longitudinal gene expressions and ordered categorical event data SO STATISTICS IN MEDICINE LA English DT Article DE microarray analysis; ordinal data; score test; multiple testing; permutation test ID MICROARRAYS; REGRESSION; MODELS AB The NIH project 'Inflammatory and Host Response to Injury' (Glue) is being conducted to Study the changes in the body over time in response to trauma and burn. Patients are monitored for changes in their clinical status, Such as the onset of and recovery from organ failure. Blood samples are drawn over the first days and weeks after the injury to obtain gene expression levels over time. Our goal was to develop a method of selecting genes that differentially expressed in patients who either improved or experienced organ failure. For this, we needed a test for the association between longitudinal gene expressions and the time to the occurrence of ordered categorical outcomes indicating recovery, stable disease, and organ failure. We propose a test for which the relationship between the gene expression and the events is modeled using the cumulative proportional odds model that is a generalization of the pooling repeated observation method. Given the high-dimensionality of the microarray data, it was necessary to control for the multiplicity of the testing. To control for the false discovery rate (FDR), we applied both a permutational approach as well as Efron's empirical estimation method. We explore our method through simulations and provide the analysis of the multi-center, longitudinal Study of immune response to inflammation and trauma (http://www.gluegrant.org). Copyright (c) 2009 John Wiley & Sons, Ltd. C1 [Finkelstein, Dianne M.; Schoenfeld, David A.] Harvard Univ, Boston, MA 02114 USA. [Finkelstein, Dianne M.; Schoenfeld, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rajicic, Natasa] Pfizer Inc, New York, NY 10017 USA. RP Finkelstein, DM (reprint author), Harvard Univ, 50 Staniford,Suite 560, Boston, MA 02114 USA. EM dfinkelstein@partners.org OI xiao, wenzhong/0000-0003-4944-6380; Baker, Henry/0000-0002-8273-5320 FU NIH [CA74302, CA075971, HD055201]; Dr Finkelstein; Large-Scale Collaborative Project Award [U54GM62119] FX The financial support was provided by the following three awards: NIH Grants CA74302, CA075971, and HD055201, Dr Finkelstein, primary investigator, and Large-Scale Collaborative Project Award (U54GM62119) frorn The National Institute of General Medical Sciences, NIH. NR 18 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 2009 VL 28 IS 22 BP 2817 EP 2832 DI 10.1002/sim.3665 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 498YS UT WOS:000270183400006 PM 19618375 ER PT J AU Gensichen, J Von Korff, M Rutter, CM Seelig, MD Ludman, EJ Lin, EHB Ciechanowski, P Young, BA Wagner, EH Katon, WJ AF Gensichen, Jochen Von Korff, Michael Rutter, Carolyn M. Seelig, Michelle D. Ludman, Evette J. Lin, Elizabeth H. B. Ciechanowski, Paul Young, Bessie A. Wagner, Edward H. Katon, Wayne J. TI Physician support for diabetes patients and clinical outcomes SO BMC PUBLIC HEALTH LA English DT Article ID GLYCEMIC CONTROL; SELF-MANAGEMENT; CENTERED CARE; DEPRESSION; STRATEGIES; DISEASE; QUALITY; FUTURE AB Background: Physician practical support ( e. g. setting goals, pro-active follow-up) and communicative support ( e. g., empathic listening, eliciting preferences) have been hypothesized to influence diabetes outcomes. Methods: In a prospective observational study, patients rated physician communicative and practical support using a modified Health Care Climate Questionnaire. We assessed whether physicians' characteristic level of practical and communicative support ( mean across patients) and each patients' deviation from their physician's mean level of support was associated with glycemic control outcomes. Glycosylated haemoglobin (HbA1c) levels were measured at baseline and at follow-up, about 2 years after baseline. Results: We analysed 3897 patients with diabetes treated in nine primary care clinics by 106 physicians in an integrated health plan in Western Washington, USA. Physicians' average level of practical support ( based on patient ratings of their provider) was associated with significantly lower HbA1c at follow-up, controlling for baseline HbA1c (p=.0401). The percentage of patients with "optimal" and "poor" glycemic control differed significantly across different levels of practical support at follow (p=.022 and p=.028). Communicative support was not associated with differences in HbA1c at follow-up. Conclusion: This observational study suggests that, in community practice settings, physician differences in practical support may influence glycemic control outcomes among patients with diabetes. C1 [Gensichen, Jochen] Univ Hosp Jena, Inst Gen Practice, Jena, Germany. [Von Korff, Michael; Rutter, Carolyn M.; Seelig, Michelle D.; Ludman, Evette J.; Lin, Elizabeth H. B.; Wagner, Edward H.] Grp Hlth Cooperat Puget Sound, Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Ciechanowski, Paul; Katon, Wayne J.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Young, Bessie A.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. RP Gensichen, J (reprint author), Univ Hosp Jena, Inst Gen Practice, Jena, Germany. EM jochen.gensichen@med.uni-jena.de; vonkorff.m@ghc.org; rutter.c@ghc.org; seelig.m@ghc.org; ludman.e@ghc.org; lin.e@ghc.org; pavelcie@u.washington.edu; youngb@u.washington.edu; wagner.e@ghc.org; wkaton@u.washington.edu FU National Institute of Mental Health (NIMH); Division of Services and Intervention Research [R01 MH4173917] FX The Pathway Study was funded by the National Institute of Mental Health (NIMH). Division of Services and Intervention Research [R01 MH4173917]. NR 29 TC 10 Z9 10 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD SEP 29 PY 2009 VL 9 AR 367 DI 10.1186/1471-2458-9-367 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 513NL UT WOS:000271329100001 PM 19788726 ER PT J AU Broom, WJ Johnson, DV Garber, M Andersen, PM Lennon, N Landers, J Nusbaum, C Russ, C Brown, RH AF Broom, Wendy J. Johnson, Daniel V. Garber, Manuel Andersen, Peter M. Lennon, Niall Landers, John Nusbaum, Chad Russ, Carsten Brown, Robert H., Jr. TI DNA sequence analysis of the conserved region around the SOD1 gene locus in recessively inherited ALS SO NEUROSCIENCE LETTERS LA English DT Article DE ALS; SOD1 ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN SUPEROXIDE-DISMUTASE; MOTOR-NEURON DISEASE; MUTATIONS; D90A; HOMOZYGOSITY; FAMILY AB Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases; 12-23% are associated with mutations in the Cu/Zn superoxide dismutase gene (SOD1). All ALS-linked SOD1 mutations present with a dominant pattern of inheritance apart from the aspartate to alanine mutation in exon 4 (D90A). This mutation has been observed in dominant, recessive and apparently sporadically cases. SOD1(D90A)/(D90A) ALS cases have a very slow disease progression (>10 years), raising the hypothesis that modifier genes linked to SOD1 ameliorate the phenotype of recessively inherited SOD1(D90A/D90A) mutations. Previous sequence analysis of a conserved haplotype region around the SOD1 gene did not reveal any functional polymorphisms within known coding or putative regulatory regions. In the current study we expanded the previous analyses by sequencing the entire SOD1 conserved haplotypic region. Although many polymorphisms were identified, none of these variants explain the slowly progressive phenotype observed in patients with recessive SOD1(D90A) Mutations. This study disproves the hypothesis that there is a tightly linked genetic protective factor specifically located close to the SOD 1 gene in SOD1(D90A) mediated ALS. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Broom, Wendy J.; Johnson, Daniel V.; Landers, John; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Andersen, Peter M.] Umea Univ, Dept Neurol, S-90187 Umea, Sweden. [Garber, Manuel; Lennon, Niall; Nusbaum, Chad; Russ, Carsten] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Amherst, MA 01003 USA. RP Broom, WJ (reprint author), Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA. EM wendy.broom@gmail.com; robert.brown@umassmed.edu FU National Institute for Neurological Disease and Stroke; Angel Fund; ALS Association; Project ALS; Pierre L. de Bourgknecht ALS Research Foundation; Al-Athel ALS Foundation; Swedish Brain Research Foundation; Hallsten's Brain Research Foundation; Bjorklund Foundation; Swedish Association for the Neurologically Disabled FX This study was supported by the National Institute for Neurological Disease and Stroke (RB, DM-Y), the Angel Fund (DJ, RB, WB, CR), the ALS Association (RB), Project ALS (RB), the Pierre L. de Bourgknecht ALS Research Foundation (RB) and the Al-Athel ALS Foundation (RB, WB). PMA is supported by the Swedish Brain Research Foundation, the Hallsten's Brain Research Foundation, the Bjorklund Foundation for ALS Research and the Swedish Association for the Neurologically Disabled. We also thank members of the Broad Institute Sequencing platform. NR 32 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 29 PY 2009 VL 463 IS 1 BP 64 EP 69 DI 10.1016/j.neulet.2009.07.010 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 489FF UT WOS:000269404800015 PM 19596401 ER EF