FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bertram, L Lange, C Mullin, K Parkinson, M Hsiao, M Hogan, MF Schjeide, BMM Hooli, B DiVito, J Ionita, L Jiang, HY Laird, N Moscarillo, T Ohlsen, KL Elliott, K Wang, X Hu-Lince, D Ryder, M Murphy, A Wagner, SL Blacker, D Becker, KD Tanzi, RE AF Bertram, Lars Lange, Christoph Mullin, Kristina Parkinson, Michele Hsiao, Monica Hogan, Meghan F. Schjeide, Brit M. M. Hooli, Basavaraj DiVito, Jason Ionita, Luliana Jiang, Hongyu Laird, Nan Moscarillo, Thomas Ohlsen, Kari L. Elliott, Kathryn Wang, Xin Hu-Lince, Diane Ryder, Marie Murphy, Amy Wagner, Steven L. Blacker, Deborah Becker, K. David Tanzi, Rudolph E. TI Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILY-BASED ASSOCIATION; MISSENSE MUTATIONS; ONSET; GENE; EPSILON-4; VARIANTS; CLONING; AGE AB Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date four genes have been established to either Cause early-onset autosomal-dominant AD (APP, PSEN1, and PSEN2(1-4)) or to increase susceptibility for late-onset AD (APOE However, the heritability of late-onset AD is as high as 80%,(6) and much of the phenotypic variance remains unexplained to date. We performed a genome-wide association (GWA) analysis using 484,522 single-nucleotide polymorphisms (SNPs) on a large (1,376 samples from 410 families) sample of AD families of self-reported European descent. We identified five SNPs showing either significant or marginally significant genome-wide association with a multivariate phenotype combining affection status and onset age. One of these signals (p = 5.7 x 10(-14)) was elicited by SNP rs4420638 and probably reflects APOE-epsilon 4, which maps 11 kb proximal (r(2) = 0.78). The other four signals were tested in three additional independent AD family samples composed of nearly 2700 individuals from almost 900 families. Two of these SNPs showed significant association in the replication samples (combined p values 0.007 and 0.00002). The SNP (rs11159647, on chromosome 14q31) with the strongest association signal also showed evidence of association with the same allele in GWA data generated in an independent sample of similar to 1,400 AD cases and controls (p = 0.04). Although the precise identity of the underlying locus(i) remains elusive, our study provides compelling evidence for the existence of at least one previously undescribed AD gene that, like APOE-epsilon 4, primarily acts as a modifier of onset age. C1 [Bertram, Lars; Mullin, Kristina; Parkinson, Michele; Hsiao, Monica; Hogan, Meghan F.; Schjeide, Brit M. M.; Hooli, Basavaraj; DiVito, Jason; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis MIND, Dept Neurol, Genet & Aging Res Unit, Boston, MA 02129 USA. [Lange, Christoph; Ionita, Luliana; Jiang, Hongyu; Laird, Nan; Murphy, Amy] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Moscarillo, Thomas; Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Charlestown, MA 02129 USA. [Ohlsen, Kari L.; Elliott, Kathryn; Wang, Xin; Hu-Lince, Diane; Ryder, Marie; Wagner, Steven L.] TorreyPines Therapeut, La Jolla, CA 92037 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis MIND, Dept Neurol, Genet & Aging Res Unit, Boston, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU Cure Alzheimer Fund; NIMH; Extendicare Foundation; Eisai FX The authors wish to thank all families for participating in this study. This work was sponsored by grants from the Cure Alzheimer Fund (as part of the "Alzheimer Genorne Project"), the NIMH, and the Extendicare Foundation. Work completed at TorreyPines Therapeutics and was funded by Eisai. L.B. and R.E.T. are consultants to, and equity holders in, TorreyPines Therapeutics and Prana Biotechnology. R.E.T is also a consultant to Prana Biotechnology. R.E.T. is a cofounder of both TorreyPines Therapeutics and Prana Biotechnology. K.L.O., K.E., X.W., D.H.-L., M.R., K.D.B., and S.W. are employees of, and hold stock options in, TorreyPines Therapeutics. K.E. and S.W also hold stock in Merck. NR 29 TC 209 Z9 215 U1 4 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV 7 PY 2008 VL 83 IS 5 BP 623 EP 632 DI 10.1016/j.ajhg.2008.10.008 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 373XN UT WOS:000261006900009 PM 18976728 ER PT J AU Assmann, A Mohlig, M Osterhoff, M Pfeiffer, AFH Spranger, J AF Assmann, Anke Moehlig, Matthias Osterhoff, Martin Pfeiffer, Andreas F. H. Spranger, Joachim TI Fatty acids differentially modify the expression of urokinase type plasminogen activator receptor in monocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE urokinase type plasminogen activator receptor (uPAR); free fatty acids; monocytes/macrophages; p38 MAP-kinase; atherosclerosis ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; MEDITERRANEAN DIET; OXIDATIVE STRESS; CELL-LINE; OLIVE OIL; BINDING; PROTEIN; IDENTIFICATION; ADHESION AB The urokinase plasminogen activator system with its receptor uPAR contributes to the migratory potential of macrophages, a key event in atherosclerosis. We here investigated whether free fatty acids (FFA) modify the expression for uPAR in the PMA-differentiated human monocyte/macrophage-like cell line U937. Two hundred micromolar palmitate induced a threefold increase of the uPAR mRNA expression. Although the mono- and polyunsaturated fatty acids oleate and linoleate also stimulated uPAR expression, oleate had a significantly lower effect than palmitate. The observed effects were time and dose dependent. Inhibition of PKC-and ERK-pathways resulted in a strong down-regulation of basal uPAR expression whereas the FFA induced up-regulation remained unchanged. In contrast, FFA induced uPAR Up-regulation was abolished by the specific inhibition of p38 MAPK. In conclusion we demonstrate that uPAR expression in human monocytes/macrophages is differentially stimulated by FFA. These effects are partially mediated by the p38 MAP-kinase signaling pathway. (C) 2008 Elsevier Inc. All rights reserved. C1 [Assmann, Anke; Moehlig, Matthias; Pfeiffer, Andreas F. H.; Spranger, Joachim] Charite Univ Med Berlin, Dept Endocrinol Diabet & Nutr, D-12200 Berlin, Germany. [Assmann, Anke] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Osterhoff, Martin; Pfeiffer, Andreas F. H.; Spranger, Joachim] German Inst Human Nutr Potsdam Rehbrucke, Dept Clin Nutr, D-14558 Nuthetal, Germany. RP Spranger, J (reprint author), Charite Univ Med Berlin, Dept Endocrinol Diabet & Nutr, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany. EM joachim.spranger@charite.de FU Bundesministerium fur Bildung und Forschung (BMBF); Deutsche Forschungsgemeinschaft (DFG) FX J.S. was supported by a research group (Molecular Nutrition) of the Bundesministerium fur Bildung und Forschung (BMBF) and a Heisenberg-Professorship of the Deutsche Forschungsgemeinschaft (DFG). NR 30 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 7 PY 2008 VL 376 IS 1 BP 196 EP 199 DI 10.1016/j.bbrc.2008.08.115 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 356NC UT WOS:000259783900039 PM 18762175 ER PT J AU Mariappan, MM Shetty, M Sataranatarajan, K Choudhury, GG Kasinath, BS AF Mariappan, Meenalakshmi M. Shetty, Megan Sataranatarajan, Kavithalakshmi Choudhury, Goutam Ghosh Kasinath, Balakuntalam S. TI Glycogen Synthase Kinase 3 beta Is a Novel Regulator of High Glucose- and High Insulin-induced Extracellular Matrix Protein Synthesis in Renal Proximal Tubular Epithelial Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA TRANSLATION; SIGNAL-TRANSDUCTION PATHWAYS; SKELETAL-MUSCLE; GROWTH-FACTOR; CARDIAC-HYPERTROPHY; DIABETIC-NEPHROPATHY; GENE-EXPRESSION; POTENTIAL ROLE; PHOSPHORYLATION; KINASE-3-BETA AB High glucose (30 mM) and high insulin (1 nM), pathogenic factors of type 2 diabetes, increased mRNA expression and synthesis of laminin beta 1 and fibronectin after 24 h of incubation in kidney proximal tubular epithelial (MCT) cells. We tested the hypothesis that inactivation of glycogen synthase kinase 3 beta(GSK3 beta) by high glucose and high insulin induces increase in synthesis of laminin beta 1 via activation of eIF2B epsilon. Both high glucose and high insulin induced Ser-9 phosphorylation and inactivation of GSK3 beta at 2 h that lasted for up to 48 h. This was associated with dephosphorylation of eIF2B epsilon and eEF2, and increase in phosphorylation of 4E-BP1 and eIF4E. Expression of the kinase-dead mutant of GSK3 beta or constitutively active kinase led to increased and diminished laminin beta 1 synthesis, respectively. Incubation with selective kinase inhibitors showed that high glucose- and high insulin-induced laminin beta 1 synthesis and phosphorylation of GSK3 beta were dependent on PI 3-kinase, Erk, and mTOR. High glucose and high insulin augmented activation of Akt, Erk, and p70S6 kinase. Dominant negative Akt, but not dominant negative p70S6 kinase, inhibited GSK3 beta phosphorylation induced by high glucose and high insulin, suggesting Akt but not p70S6 kinase was upstream of GSK3 beta. Status of GSK3 beta was examined in vivo in renal cortex of db/db mice with type 2 diabetes at 2 weeks and 2 months of diabetes. Diabetic mice showed increased phosphorylation of renal cortical GSK3 beta and decreased phosphorylation of eIF2B epsilon, which correlated with renal hypertrophy at 2 weeks, and increased laminin beta 1 and fibronectin protein content at 2 months. GSK3 beta and eIF2B epsilon play a role in augmented protein synthesis associated with high glucose- and high insulin-stimulated hypertrophy and matrix accumulation in renal disease in type 2 diabetes. C1 [Mariappan, Meenalakshmi M.; Shetty, Megan; Sataranatarajan, Kavithalakshmi; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, OBrien Kidney Res Ctr, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Kasinath@uthscsa.edu FU National Institutes of Health [DK061597, DK077295, DK050190]; Juvenile Diabetes Research Foundation [3-2007-245, 1-2008-185]; American Diabetes Association [7-05-RA-60]; Veterans Administration Research Service; American Heart Association [SDG 0630283N] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK061597 and DK077295 (to B. S. K.) and DK050190 (to G. G. C.). These studies were also supported by Juvenile Diabetes Research Foundation Grants 3-2007-245 (to M. M. M. and B. S. K.) and 1-2008-185 (to G. G. C.), American Diabetes Association Grant 7-05-RA-60 (to B. S. K.), the Veterans Administration Research Service (to B. S. K. and G. G. C.), and American Heart Association Grant SDG 0630283N (to D. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 58 TC 36 Z9 39 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 2008 VL 283 IS 45 BP 30566 EP 30575 DI 10.1074/jbc.M801756200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 367ID UT WOS:000260544800015 PM 18701453 ER PT J AU Cohn, MA D'Andrea, AD AF Cohn, Martin A. D'Andrea, Alan D. TI Chromatin Recruitment of DNA Repair Proteins: Lessons from the Fanconi Anemia and Double-Strand Break Repair Pathways SO MOLECULAR CELL LA English DT Article ID UBIQUITIN-BINDING DOMAINS; CROSS-LINK REPAIR; DAMAGE RESPONSE; BRCA1; UBIQUITYLATION; REPLICATION; COMPLEX; LIGASE; FANCD2; MONOUBIQUITINATION AB In response to DNA damage, eukaryotic cells must rapidly load DNA repair proteins onto damaged chromatin. Chromatin recruitment often entails ubiquitination of a damage-specific DNA repair protein, interaction with a ubiquitin binding factor, assembly of a multisubunit DNA repair complex, and eventually a deubiquitination event once the DNA repair reaction has been completed. This review focuses on the recent discoveries in the Fanconi Anemia (FA) and DNA double-strand break (DSB) repair pathways, which underscore the importance of regulated chromatin loading in the DNA damage response. Interestingly, these two pathways share several features, suggesting a more general mechanism for DNA-repair regulation. C1 [Cohn, Martin A.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu OI Cohn, Martin/0000-0002-2988-3009 FU NIH [5PO1CA092584] FX We are grateful to Drs. Younghoon Kee, Lucian Moldovan, and Vladimir Joukov for critical reading of the manuscript and helpful discussions. We apologize to colleagues whose work was not cited or was only referred to by citing review articles due to space restrictions. This work was supported by NIH grant 5PO1CA092584. NR 48 TC 46 Z9 47 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV 7 PY 2008 VL 32 IS 3 BP 306 EP 312 DI 10.1016/j.molcel.2008.10.009 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 371UY UT WOS:000260858300002 PM 18995829 ER PT J AU van Oevelen, C Wang, JH Asp, P Yan, Q Kaelin, WG Kluger, Y Dynlacht, BD AF van Oevelen, Chris Wang, Jinhua Asp, Patrik Yan, Qin Kaelin, William G., Jr. Kluger, Yuval Dynlacht, Brian David TI A Role for Mammalian Sin3 in Permanent Gene Silencing SO MOLECULAR CELL LA English DT Article ID CELL-CYCLE CONTROL; CHROMATIN REMODELING COMPLEXES; TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE; SIN3/HISTONE DEACETYLASE; COREPRESSOR COMPLEX; IN-VIVO; METHYLATION; GENOME; YEAST AB The multisubunit Sin3 corepressor complex regulates gene transcription through deacetylation of nucleosomes. However, the full range of Sin3 activities and targets is not well understood. Here, we have investigated genome-wide binding of mouse Sin3 and RBP2 as well as histone modifications and nucleosome positioning as a function of myogenic differentiation. Remarkably, we find that Sin3 complexes spread immediately downstream of the transcription start site on repressed and transcribed genes during differentiation. We show that RBP2 is part of a Sin3 complex and that on a subset of E2F4 target genes, the coordinated activity of Sin3 and RBP2 leads to deacetylation, demethylation, and repositioning of nucleosomes. Our work provides evidence for coordinated binding of Sin3, chromatin modifications, and chromatin remodeling within discrete regulatory regions, suggesting a model in which spreading of Sin3 binding is ultimately linked to permanent gene silencing on a subset of E2F4 target genes. C1 [van Oevelen, Chris; Wang, Jinhua; Asp, Patrik; Kluger, Yuval; Dynlacht, Brian David] NYU, Sch Med, Inst Canc, New York, NY 10016 USA. [Yan, Qin; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Yan, Qin; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yan, Qin; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kluger, Y (reprint author), NYU, Sch Med, Inst Canc, 522 1st Ave, New York, NY 10016 USA. EM yuval.kluger@nuymc.org; brian.dynlacht@nuymc.org RI Yan, Qin/E-8893-2012 OI Yan, Qin/0000-0003-4077-453X FU National Institutes of Heath (NIH) [CA077245, CA076120]; Susan Komen Postdoctoral Fellowship; Department of Defense Breast Cancer Research program Concept Award [W81XWH-07-1-0581] FX We are grateful to members of the DyrlaCAt lab and to G. David for comments on the manuscript and helpful suggestions during the course of this study. We thank A Bhattacharjee and G. Das for assistance with experiments This work was supported by National Institutes of Heath (NIH) grant CA077245 (to B. D. D.), NIH grant CA076120 (to W.G.K.), Susan Komen Postdoctoral Fellowship (to C.v.O.), and Department of Defense Breast Cancer Research program Concept Award W81XWH-07-1-0581 (to Q.Y. W.G.K. is an investigator of the Howard Hughes Medical Institute. NR 37 TC 61 Z9 61 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV 7 PY 2008 VL 32 IS 3 BP 359 EP 370 DI 10.1016/j.molcel.2008.10.015 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 371UY UT WOS:000260858300007 PM 18995834 ER PT J AU Kulkarni, H Marconi, VC Agan, BK McArthur, C Crawford, G Clark, RA Dolan, MJ Ahuja, SK AF Kulkarni, Hemant Marconi, Vincent C. Agan, Brian K. McArthur, Carole Crawford, George Clark, Robert A. Dolan, Matthew J. Ahuja, Sunil K. TI Role of CCL3L1-CCR5 Genotypes in the Epidemic Spread of HIV-1 and Evaluation of Vaccine Efficacy SO PLOS ONE LA English DT Article AB Background: Polymorphisms in CCR5, the major coreceptor for HIV, and CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine, are determinants of HIV-AIDS susceptibility. Here, we mathematically modeled the potential impact of these genetic factors on the epidemic spread of HIV, as well as on its prevention. Methods and Results: Ro, the basic reproductive number, is a fundamental concept in explaining the emergence and persistence of epidemics. By modeling sexual transmission among HIV+/HIV- partner pairs, we find that Ro estimates, and concordantly, the temporal and spatial patterns of HIV outgrowth are highly dependent on the infecting partners' CCL3L1-CCR5 genotype. Ro was least and highest when the infected partner possessed protective and detrimental CCL3L1-CCR5 genotypes, respectively. The modeling data indicate that in populations such as Pygmies with a high CCL3L1 gene dose and protective CCR5 genotypes, the spread of HIV might be minimal. Additionally, Pc, the critical vaccination proportion, an estimate of the fraction of the population that must be vaccinated successfully to eradicate an epidemic was <1 only when the infected partner had a protective CCL3L1-CCR5 genotype. Since in practice Pc cannot be >1, to prevent epidemic spread, population groups defined by specific CCL3L1-CCR5 genotypes might require repeated vaccination, or as our models suggest, a vaccine with an efficacy of >70%. Further, failure to account for CCL3L1-CCR5-based genetic risk might confound estimates of vaccine efficacy. For example, in a modeled trial of 500 subjects, misallocation of CCL3L1-CCR5 genotype of only 25 (5%) subjects between placebo and vaccine arms results in a relative error of similar to 12% from the true vaccine efficacy. Conclusions: CCL3L1-CCR5 genotypes may impact on the dynamics of the HIV epidemic and, consequently, the observed heterogeneous global distribution of HIV infection. As Ro is lowest when the infecting partner has beneficial CCL3L1-CCR5 genotypes, we infer that therapeutic vaccines directed towards reducing the infectivity of the host may play a role in halting epidemic spread. Further, CCL3L1-CCR5 genotype may provide critical guidance for optimizing the design and evaluation of HIV-1 vaccine trials and prevention programs. C1 [Kulkarni, Hemant; Crawford, George; Clark, Robert A.; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Marconi, Vincent C.; Agan, Brian K.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD USA. [Marconi, Vincent C.; Dolan, Matthew J.] Wilford Hall US Air Force Med Ctr, Infect Dis Serv, Lackland AFB, TX USA. [Marconi, Vincent C.; Dolan, Matthew J.] San Antonio Mil Med Ctr, Ft Sam Houston, TX USA. [McArthur, Carole] Univ Missouri, Sch Dent, Dept Oral Biol, Kansas City, MO USA. [Dolan, Matthew J.] Wilford Hall US Air Force Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr, Dept Med, Microbiol & Immunol & Biochem, San Antonio, TX USA. RP Kulkarni, H (reprint author), S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. EM kulkarnih@uthscsa.edu; ahujas@uthscsa.edu RI Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Agan, Brian/0000-0002-5114-1669 FU Veterans Administration (VA) Center on AIDS and HIV infection of the South Texas Veterans Health Care System; MERIT [R37046326]; NIH [AI043279, MH069270]; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award in Translational Research; Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS); Henry M. Jackson Foundation for the Advancement of Military Medicine; HHS/NIH/NIAID/DCR [HU0001-05-2-0011] FX This work was supported by the Veterans Administration (VA) Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and a MERIT (R37046326) and other awards (AI043279 and MH069270) from the NIH to S.K.A. S.K.A. is also supported by a VA MERIT award and is a recipient of the Elizabeth Glaser Scientist Award and the Burroughs Wellcome Clinical Scientist Award in Translational Research. Support for the DoD HIV Natural History Study cohort and staff involved in this work was provided by the Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS), of which the Tri-Service AIDS Clinical Consortium (TACC) is a component. The IDCRP is a Department of Defense tri-service program executed through USUHS and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), in collaboration with HHS/NIH/NIAID/DCR through Interagency Agreement HU0001-05-2-0011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting the views of the Departments of the Army, Navy, Air Force, or the Department of Defense. NR 96 TC 15 Z9 16 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2008 VL 3 IS 11 AR e3671 DI 10.1371/journal.pone.0003671 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432LM UT WOS:000265134600007 PM 18989363 ER PT J AU Cotton, RGH Auerbach, AD Axton, M Barash, CI Berkovic, SF Brookes, AJ Burn, J Cutting, G den Dunnen, JT Flicek, P Freimer, N Greenblatt, MS Howard, HJ Katz, M Macrae, FA Maglott, D Moslein, G Povey, S Ramesar, RS Richards, CS Seminara, D Smith, TD Sobrido, MJ Solbakk, JH Tanzi, RE Tavtigian, SV Taylor, GR Utsunomiya, J Watson, M AF Cotton, Richard G. H. Auerbach, Arleen D. Axton, Myles Barash, Carol Isaacson Berkovic, Samuel F. Brookes, Anthony J. Burn, John Cutting, Garry den Dunnen, Johan T. Flicek, Paul Freimer, Nelson Greenblatt, Marc S. Howard, Heather J. Katz, Michael Macrae, Finlay A. Maglott, Donna Moeslein, Gabriela Povey, Sue Ramesar, Rajkumar S. Richards, Carolyn S. Seminara, Daniela Smith, Timothy D. Sobrido, Maria-Jesus Solbakk, Jan Helge Tanzi, Rudolph E. Tavtigian, Sean V. Taylor, Graham R. Utsunomiya, Joji Watson, Michael TI GENETICS The Human Variome Project SO SCIENCE LA English DT Editorial Material C1 [Cotton, Richard G. H.; Howard, Heather J.; Smith, Timothy D.] Howard Florey Inst Expt Physiol & Med, Genom Disorders Res Ctr, Melbourne, Vic, Australia. [Berkovic, Samuel F.] Univ Melbourne, Austin Hlth W, Epilepsy Res Ctr, Heidelberg, Vic, Australia. [Freimer, Nelson] Univ Calif Los Angeles, Ctr Neurobehav Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Sobrido, Maria-Jesus] Fdn Publ Galega Med Xenomica, Santiago De Compostela, Spain. [Sobrido, Maria-Jesus] Inst Hlth Carlos III, Ctr Network Biomed Res Rare Dis CIBERER, Madrid, Spain. [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Charlestown, MA USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Cotton, RGH (reprint author), Howard Florey Inst Expt Physiol & Med, Genom Disorders Res Ctr, Melbourne, Vic, Australia. EM cotton@unimelb.edu.au RI Ramesar, Raj/I-6941-2015; OI Ramesar, Raj/0000-0001-5688-1634; Smith, Timothy/0000-0001-9068-4642; Auerbach, Arleen/0000-0002-6911-8379; Berkovic, Samuel/0000-0003-4580-841X; Flicek, Paul/0000-0002-3897-7955; Burn, John/0000-0002-9823-2322 FU NIDDK NIH HHS [R37 DK044003-19, R37 DK044003] NR 6 TC 35 Z9 38 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 7 PY 2008 VL 322 IS 5903 BP 861 EP 862 DI 10.1126/science.1167363 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DI UT WOS:000260674100022 PM 18988827 ER PT J AU Altshuler, D Daly, MJ Lander, ES AF Altshuler, David Daly, Mark J. Lander, Eric S. TI Genetic Mapping in Human Disease SO SCIENCE LA English DT Review ID GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H; SINGLE-NUCLEOTIDE POLYMORPHISMS; DENSITY-LIPOPROTEIN CHOLESTEROL; FRAGMENT LENGTH POLYMORPHISMS; CORONARY-ARTERY-DISEASE; PROSTATE-CANCER RISK; C-REACTIVE PROTEIN; BETA-CELL FUNCTION; LINKAGE DISEQUILIBRIUM AB Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome- wide association studies of common diseases, and discuss questions and challenges that lie ahead. C1 [Altshuler, David; Daly, Mark J.; Lander, Eric S.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Altshuler, David; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Altshuler, David; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Altshuler, David; Daly, Mark J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Altshuler, D (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM altshuler@molbio.mgh.harvard.edu; mjdaly@chgr.mgh.harvard.edu; lander@broad.mit.edu RI Altshuler, David/A-4476-2009; Sincan, Murat /A-3794-2010 OI Altshuler, David/0000-0002-7250-4107; FU NHGRI NIH HHS [U54 HG003067, U54 HG003067-03] NR 134 TC 711 Z9 734 U1 9 U2 98 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 7 PY 2008 VL 322 IS 5903 BP 881 EP 888 DI 10.1126/science.1156409 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DI UT WOS:000260674100031 PM 18988837 ER PT J AU Stadtfeld, M Nagaya, M Utikal, J Weir, G Hochedlinger, K AF Stadtfeld, Matthias Nagaya, Masaki Utikal, Jochen Weir, Gordon Hochedlinger, Konrad TI Induced Pluripotent Stem Cells Generated Without Viral Integration SO SCIENCE LA English DT Article ID HUMAN SOMATIC-CELLS; DEFINED FACTORS; FIBROBLASTS; EXPRESSION; INDUCTION; VECTORS; LIVER AB Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome- integrating viruses. We generated mouse induced pluripotent stem ( iPS) cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c- Myc. These adenoviral iPS ( adeno- iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient- specific stem cells and for comparing embryonic stem cells and iPS cells. C1 [Stadtfeld, Matthias; Utikal, Jochen; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stadtfeld, Matthias; Utikal, Jochen; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Stadtfeld, Matthias; Utikal, Jochen; Hochedlinger, Konrad] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. [Nagaya, Masaki; Weir, Gordon] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. [Stadtfeld, Matthias; Utikal, Jochen; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Stadtfeld, Matthias; Nagaya, Masaki; Utikal, Jochen; Weir, Gordon; Hochedlinger, Konrad] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu OI Utikal, Jochen/0000-0001-5316-0241; Stadtfeld, Matthias/0000-0002-5852-9906 FU Schering postdoctoral fellowship; Mildred Scheel postdoctoral fellowship; Juvenile Diabetes Research Foundation; NIH Director's Innovator Award; Harvard Stem Cell Institute; Kimmel Foundation; V Foundation FX We thank H. Hock for critical comments on the manuscript and L. Prickett and K. Folz-Donahue for expert help with flow cytometry. We are especially grateful to J. Lee of the Harvard Gene Therapy Initiative for help with the generation of adenoviral vectors. M. S. was supported by a Schering postdoctoral fellowship, J.U. was supported by a Mildred Scheel postdoctoral fellowship and M.N. and G.W. received support from the Juvenile Diabetes Research Foundation. Support to K.H. was from the NIH Director's Innovator Award, the Harvard Stem Cell Institute, the Kimmel Foundation and the V Foundation. The authors are filing a patent based on the results reported in this paper. NR 28 TC 934 Z9 1037 U1 13 U2 150 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 7 PY 2008 VL 322 IS 5903 BP 945 EP 949 DI 10.1126/science.1162494 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DI UT WOS:000260674100048 PM 18818365 ER PT J AU Wang, MC O'Rourke, EJ Ruvkun, G AF Wang, Meng C. O'Rourke, Eyleen J. Ruvkun, Gary TI Fat Metabolism Links Germline Stem Cells and Longevity in C. elegans SO SCIENCE LA English DT Article ID CAENORHABDITIS-ELEGANS; LIFE-SPAN; SEX-DETERMINATION; SIGNALING PATHWAY; DAF-16; GENES; GLP-1; REPRODUCTION; DROSOPHILA; RECEPTOR AB Fat metabolism, reproduction, and aging are intertwined regulatory axes; however, the mechanism by which they are coupled remains poorly understood. We found that germline stem cells (GSCs) actively modulate lipid hydrolysis in Caenorhabditis elegans, which in turn regulates longevity. GSC arrest promotes systemic lipolysis via induction of a specific fat lipase. Subsequently, fat mobilization is promoted and life span is prolonged. Constitutive expression of this lipase in fat storage tissue generates lean and long- lived animals. This lipase is a key factor in the lipid hydrolysis and increased longevity that are induced by decreased insulin signaling. These results suggest a link between C. elegans fat metabolism and longevity. C1 [Wang, Meng C.; O'Rourke, Eyleen J.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Wang, Meng C.; O'Rourke, Eyleen J.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU Life Sciences Research Foundation; Ellison Medical Foundation; Human Frontier Science Program; NIH [5R01AG016636, 5R37AG14161] FX We thank H. Mak, J. Dittman, and J. Avruch for critical reading of the manuscript; N. Ringstad for laser ablation techniques; V. Rottiers, A. Antebi, and the Caenorhabditis Genetics Center for providing strains; A. Fire for GFP vectors; and members of the Ruvkun lab for discussions. Supported by Life Sciences Research Foundation and Ellison Medical Foundation fellowships (M.C.W.), a Human Frontier Science Program fellowship (E.J.O.), and NIH grants 5R01AG016636 and 5R37AG14161 (G.R.). NR 24 TC 163 Z9 179 U1 1 U2 32 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 7 PY 2008 VL 322 IS 5903 BP 957 EP 960 DI 10.1126/science.1162011 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DI UT WOS:000260674100051 PM 18988854 ER PT J AU Tzatsos, A Bardeesy, N AF Tzatsos, Alexandros Bardeesy, Nabeel TI Ink4a/Arf Regulation by let-7b and Hmga2: A Genetic Pathway Governing Stem Cell Aging SO CELL STEM CELL LA English DT Editorial Material ID EPITHELIAL-MESENCHYMAL TRANSITION; CANCER; P16(INK4A); OLD AB Stem cell self-renewal capacity declines with age. In a recent issue of Cell, Nishino and colleagues (2008) show that Hmga2 maintains neural stem cell (NSC) function in young mice through repression of the Ink4a/Arf locus; in contrast, during aging, elevated let-7b blocks Hmga2 and contributes to declining NSC function. C1 [Tzatsos, Alexandros; Bardeesy, Nabeel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Bardeesy, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM bardeesy.nabeel@mgh.harvard.edu NR 10 TC 24 Z9 24 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 6 PY 2008 VL 3 IS 5 BP 469 EP 470 DI 10.1016/j.stem.2008.10.008 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 372IK UT WOS:000260895100003 PM 18983959 ER PT J AU Graf, T Stadtfeld, M AF Graf, Thomas Stadtfeld, Matthias TI Heterogeneity of Embryonic and Adult Stem Cells SO CELL STEM CELL LA English DT Review ID LINEAGE-COMMITMENT; PROGENITOR CELLS; IN-VIVO; DIFFERENTIATION; STATES; IDENTIFICATION; PLURIPOTENCY; MAINTENANCE; NANOG; NOISE AB New studies suggest that stem cells of embryonic, neural, and hematopoietic origin are heterogeneous, with cells moving between two or more metastable states. These cell states show a bias in their differentiation potential and correlate with specific patterns of transcription factor expression and chromatin modifications. C1 [Graf, Thomas] ICREA, Ctr Genom Regulat, Barcelona 08003, Spain. [Graf, Thomas] Pompeu Fabra Univ, Barcelona 08003, Spain. [Stadtfeld, Matthias] Ctr Regenerat Med, Boston, MA 02114 USA. [Stadtfeld, Matthias] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stadtfeld, Matthias] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Graf, T (reprint author), ICREA, Ctr Genom Regulat, Barcelona 08003, Spain. EM thomas.graf@crg.es RI Graf, Thomas/B-4252-2015; OI Graf, Thomas/0000-0003-2774-4117; Stadtfeld, Matthias/0000-0002-5852-9906 NR 24 TC 175 Z9 180 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 6 PY 2008 VL 3 IS 5 BP 480 EP 483 DI 10.1016/j.stem.2008.10.007 PG 4 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 372IK UT WOS:000260895100007 PM 18983963 ER PT J AU Huang, J Lesser, CF Lory, S AF Huang, Jin Lesser, Cammie F. Lory, Stephen TI The essential role of the CopN protein in Chlamydia pneumoniae intracellular growth SO NATURE LA English DT Article ID III SECRETION; HELA-CELLS; SACCHAROMYCES-CEREVISIAE; VIRULENCE PROTEINS; INFECTED CELLS; YEAST; EXPRESSION; BACTERIAL; IDENTIFICATION; TRANSLOCATION AB Bacterial virulence determinants can be identified, according to the molecular Koch's postulates(1), if inactivation of a gene associated with a suspected virulence trait results in a loss in pathogenicity. This approach is commonly used with genetically tractable organisms. However, the current lack of tools for targeted gene disruptions in obligate intracellular microbial pathogens seriously hampers the identification of their virulence factors. Here we demonstrate an approach to studying potential virulence factors of genetically intractable organisms, such as Chlamydia. Heterologous expression of Chlamydia pneumoniae CopN in yeast and mammalian cells resulted in a cell cycle arrest, presumably owing to alterations in the microtubule cytoskeleton. A screen of a small molecule library identified two compounds that alleviated CopN-induced growth inhibition in yeast. These compounds interfered with C. pneumoniae replication in mammalian cells, presumably by 'knocking out' CopN function, revealing an essential role of CopN in the support of C. pneumoniae growth during infection. This work demonstrates the role of a specific chlamydial protein in virulence. The chemical biology approach described here can be used to identify virulence factors, and the reverse chemical genetic strategy can result in the identification of lead compounds for the development of novel therapeutics. C1 [Huang, Jin; Lesser, Cammie F.; Lory, Stephen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Lesser, Cammie F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. RP Lory, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. EM stephen_lory@hms.harvard.edu FU NIAID NIH HHS [R01 AI064285, R01 AI064285-03] NR 38 TC 38 Z9 38 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 6 PY 2008 VL 456 IS 7218 BP 112 EP U10 DI 10.1038/nature07355 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DH UT WOS:000260674000051 PM 18830244 ER PT J AU Hoshida, Y Villanueva, A Kobayashi, M Peix, J Chiang, DY Camargo, A Gupta, S Moore, J Wrobel, MJ Lerner, J Reich, M Chan, JA Glickman, JN Ikeda, K Hashimoto, M Watanabe, G Daidone, MG Roayaie, S Schwartz, M Thung, S Salvesen, HB Gabriel, S Mazzaferro, V Bruix, J Friedman, SL Kumada, H Llovet, JM Golub, TR AF Hoshida, Yujin Villanueva, Augusto Kobayashi, Masahiro Peix, Judit Chiang, Derek Y. Camargo, Amy Gupta, Supriya Moore, Jamie Wrobel, Matthew J. Lerner, Jim Reich, Michael Chan, Jennifer A. Glickman, Jonathan N. Ikeda, Kenji Hashimoto, Masaji Watanabe, Goro Daidone, Maria G. Roayaie, Sasan Schwartz, Myron Thung, Swan Salvesen, Helga B. Gabriel, Stacey Mazzaferro, Vincenzo Bruix, Jordi Friedman, Scott L. Kumada, Hiromitsu Llovet, Josep M. Golub, Todd R. TI Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED-TRIAL; LIVER-CANCER; RECURRENCE; RESECTION; INTERFERON; PREVENTION; MANAGEMENT; TUMOR; RISK AB Background: It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. Methods: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. Results: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04). Conclusions: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma. C1 [Hoshida, Yujin; Chiang, Derek Y.; Camargo, Amy; Gupta, Supriya; Moore, Jamie; Wrobel, Matthew J.; Lerner, Jim; Reich, Michael; Chan, Jennifer A.; Gabriel, Stacey; Golub, Todd R.] MIT, Broad Inst, Canc Program, Cambridge, MA 02142 USA. [Hoshida, Yujin; Chiang, Derek Y.; Camargo, Amy; Gupta, Supriya; Moore, Jamie; Wrobel, Matthew J.; Lerner, Jim; Reich, Michael; Chan, Jennifer A.; Gabriel, Stacey; Golub, Todd R.] Harvard Univ, Cambridge, MA 02142 USA. [Golub, Todd R.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Hoshida, Yujin; Chiang, Derek Y.; Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Glickman, Jonathan N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Villanueva, Augusto; Peix, Judit; Roayaie, Sasan; Schwartz, Myron; Thung, Swan; Friedman, Scott L.; Llovet, Josep M.] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, Div Liver Dis, New York, NY 10029 USA. [Kobayashi, Masahiro; Ikeda, Kenji; Hashimoto, Masaji; Watanabe, Goro; Kumada, Hiromitsu] Toranomon Gen Hosp, Tokyo, Japan. [Daidone, Maria G.; Mazzaferro, Vincenzo] Natl Canc Inst, I-20133 Milan, Italy. [Salvesen, Helga B.] Univ Bergen, Haukeland Univ Hosp, Bergen, Norway. [Bruix, Jordi; Llovet, Josep M.] Hosp Clin Barcelona, Ctr Invest Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi & Sunyer, Barcelona Clin Liver Canc Grp, Barcelona, Spain. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. RP Golub, TR (reprint author), MIT, Broad Inst, Canc Program, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM josep.llovet@mssm.edu; golub@broad.mit.edu RI Augusto, Villanueva/F-9378-2012; Llovet, Josep M /D-4340-2014; salvesen, Helga/C-1187-2017; Mazzaferro, Vincenzo/C-2726-2017; Daidone, Maria Grazia/E-9232-2017; OI Augusto, Villanueva/0000-0003-3585-3727; Llovet, Josep M /0000-0003-0547-2667; salvesen, Helga/0000-0002-4438-8831; Mazzaferro, Vincenzo/0000-0002-4013-8085; Daidone, Maria Grazia/0000-0002-4786-1321; Chiang, Derek/0000-0002-1131-6065; Bruix, Jordi/0000-0002-9826-0753 FU National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK076986-01]; National Cancer Institute [5U54 CA112962-03]; Samuel Waxman Cancer Research Foundation; Spanish National Health Institute [SAF2007-61898]; Institucio Catalana de Recerca i Estudis Avancats; Centro de Investigaciones en Red de Enfermedades Hepaticas y Digestivas; Fund for Health of Spain of the Institute of Health Carlos III [PI05-0150]; National Institutes of Health [DK37340]; Italian Association for Cancer Research; Norwegian Cancer Society; Harald Andersens grant; Charles A. King Trust fellowship; Fundacion Pedro Barri, de la Maza; Sheila Sherlock Fellowship; National Cancer Center Fellowship FX Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01, to Dr. Llovet), the National Cancer Institute (5U54 CA112962-03, to Dr. Golub), the Samuel Waxman Cancer Research Foundation (to Dr. Llovet), the Spanish National Health Institute (SAF2007-61898, to Dr. Llovet), Institucio Catalana de Recerca i Estudis Avancats (to Dr. Llovet), Centro de Investigaciones en Red de Enfermedades Hepaticas y Digestivas (to Drs. Llovet and Bruix), the Fund for Health of Spain of the Institute of Health Carlos III (PI05-0150, to Dr. Bruix), the National Institutes of Health (DK37340, to Dr. Friedman), the Italian Association for Cancer Research (to Dr. Mazzaferro), Helse Vest and Norwegian Cancer Society, Harald Andersens grant (to Dr. Salvesen), the Charles A. King Trust fellowship (to Dr. Hoshida), and Fundacion Pedro Barri, de la Maza, the Sheila Sherlock Fellowship, and the National Cancer Center Fellowship (all to Dr. Villanueva). NR 22 TC 622 Z9 644 U1 4 U2 23 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 NOV 6 PY 2008 VL 359 IS 19 BP 1995 EP 2004 DI 10.1056/NEJMoa0804525 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 368OW UT WOS:000260632700004 PM 18923165 ER PT J AU Latourelle, JC Sun, M Lew, MF Suchowersky, O Klein, C Golbe, LI Mark, MH Growdon, JH Wooten, GF Watts, RL Guttman, M Racette, BA Perlmutter, JS Ahmed, A Shill, HA Singer, C Goldwurm, S Pezzoli, G Zini, M Saint-Hilaire, MH Hendricks, AE Williamson, S Nagle, MW Wilk, JB Massood, T Huskey, KW Laramie, JM DeStefano, AL Baker, KB Itin, I Litvan, I Nicholson, G Corbett, A Nance, M Drasby, E Isaacson, S Burn, DJ Chinnery, PF Pramstaller, PP Al-hinti, J Moller, AT Ostergaard, K Sherman, SJ Roxburgh, R Snow, B Slevin, JT Cambi, F Gusella, JF Myers, RH AF Latourelle, Jeanne C. Sun, Mei Lew, Mark F. Suchowersky, Oksana Klein, Christine Golbe, Lawrence I. Mark, Margery H. Growdon, John H. Wooten, G. Frederick Watts, Ray L. Guttman, Mark Racette, Brad A. Perlmutter, Joel S. Ahmed, Anwar Shill, Holly A. Singer, Carlos Goldwurm, Stefano Pezzoli, Gianni Zini, Michela Saint-Hilaire, Marie H. Hendricks, Audrey E. Williamson, Sally Nagle, Michael W. Wilk, Jemma B. Massood, Tiffany Huskey, Karen W. Laramie, Jason M. DeStefano, Anita L. Baker, Kenneth B. Itin, Ilia Litvan, Irene Nicholson, Garth Corbett, Alastair Nance, Martha Drasby, Edward Isaacson, Stuart Burn, David J. Chinnery, Patrick F. Pramstaller, Peter P. Al-hinti, Jomana Moller, Anette T. Ostergaard, Karen Sherman, Scott J. Roxburgh, Richard Snow, Barry Slevin, John T. Cambi, Franca Gusella, James F. Myers, Richard H. TI The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study SO BMC MEDICINE LA English DT Article ID ASHKENAZI JEWS; G2019S AB Background: We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. Methods: A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. Results: Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. Conclusion: Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men. C1 [Latourelle, Jeanne C.; Saint-Hilaire, Marie H.; Hendricks, Audrey E.; Williamson, Sally; Nagle, Michael W.; Wilk, Jemma B.; Massood, Tiffany; Huskey, Karen W.; Laramie, Jason M.; DeStefano, Anita L.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Sun, Mei; Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit,Ctr Human Genet Res, Boston, MA USA. [Lew, Mark F.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Suchowersky, Oksana] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Suchowersky, Oksana] Univ Calgary, Dept Med Genet, Calgary, AB, Canada. [Klein, Christine] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Golbe, Lawrence I.; Mark, Margery H.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. [Growdon, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Wooten, G. Frederick] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. [Watts, Ray L.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Guttman, Mark] Univ Toronto, Dept Med, Toronto, ON, Canada. [Racette, Brad A.; Perlmutter, Joel S.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Ahmed, Anwar] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Shill, Holly A.] Sun Hlth Res Inst, Sun City, AZ USA. [Singer, Carlos] Univ Miami, Dept Neurol, Miami, FL USA. [Goldwurm, Stefano; Pezzoli, Gianni; Zini, Michela] Ist Clinici Perfezionamento, Parkinson Inst, Milan, Italy. [Hendricks, Audrey E.; DeStefano, Anita L.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Baker, Kenneth B.; Itin, Ilia] Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. [Baker, Kenneth B.; Itin, Ilia] Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. [Litvan, Irene] Univ Louisville, Sch Med, Dept Neurol, Louisville, KY 40292 USA. [Nicholson, Garth; Corbett, Alastair] Univ Sydney, Dept Neurol, ANZAC Res Inst, Concord Hosp, Sydney, NSW 2006, Australia. [Nance, Martha] Struthers Parkinsons Ctr, Pk Nicollet Clin, Golden Valley, MN USA. [Drasby, Edward] Port City Neurol, Scarborough, ME USA. [Isaacson, Stuart] Parkinsons Dis & Movement Disorder Ctr Boca Raton, Boca Raton, FL USA. [Burn, David J.] Univ Newcastle, Inst Ageing & Hlth, Newcastle Upon Tyne, Tyne & Wear, England. [Chinnery, Patrick F.] Univ Newcastle, Reg Neurosci Ctr, Newcastle Upon Tyne, Tyne & Wear, England. [Pramstaller, Peter P.] Gen Reg Hosp Bolzano, Dept Neurol, Bolzano, Italy. [Al-hinti, Jomana] Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. [Moller, Anette T.; Ostergaard, Karen] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus, Denmark. [Sherman, Scott J.] Univ Arizona, Dept Neurol, Tucson, AZ USA. [Roxburgh, Richard; Snow, Barry] Auckland City Hosp, Dept Neurol, Auckland, New Zealand. [Slevin, John T.; Cambi, Franca] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY USA. RP Latourelle, JC (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM jlatoure@bu.edu; msun1@partners.org; mlew@surgery.usc.edu; osuchowe@ucalgary.ca; Christine.klein@neuro.uni-luebeck.de; golbe@umdnj.edu; mark@umdnj.edu; growdon@helix.mgh.harvard.edu; gfw4b@virginia.edu; rlwatts@uab.edu; mguttman@movementdisorders.ca; racetteb@neuro.wustl.edu; Joel@NPG.wustl.edu; Anwar.ahmed@chw.edu; holly.shill@sunhealth.org; csinger@med.miami.edu; goldwurm@parkinson.it; Pezzoli@parkinson.it; michelazini@libero.it; neuromsh@bu.edu; baera@bu.edu; sallyw@bu.edu; mwn@bu.edu; jwilk@bu.edu; tmassood@bu.edu; kwuh@bu.edu; laramiej@gmail.com; adestef@bu.edu; bakerk@ccf.org; itini@ccf.org; i.litvan@louisville.edu; garthn@med.usyd.edu.au; corbea@email.cs.nsw.gov.au; nancem@parknicollet.com; edrasby@portcityneurology.com; isaacson@parkinsonscenter.org; d.j.burn@ncl.ac.uk; p.f.chinnery@ncl.ac.uk; Peter.Pramstaller@eurac.edu; AlhintiJomanaT@uams.edu; Torvin@KI.AU.DK; Karen.ostergaard@oncable.dk; SSherman@u.arizona.edu; richardR@adhb.govt.nz; Bsnow@ahsl.co.nz; jslevin@uky.edu; Franca.Cambi@uky.edu; gusella@helix.mgh.harvard.edu; myers@bu.edu RI Pramstaller, Peter/C-2357-2008; Hendricks, Audrey/I-4127-2016; Goldwurm, Stefano/Q-8978-2016 OI Saint-Hilaire, Marie-Helene/0000-0002-2355-5979; Latourelle, Jeanne/0000-0002-4218-9572; Roxburgh, Richard/0000-0002-8930-7003; Myers, Richard/0000-0002-8365-2674; Litvan, Irene/0000-0002-3485-3445; Hendricks, Audrey/0000-0002-7152-0287; Goldwurm, Stefano/0000-0002-1651-567X FU Bumpus Foundation; PHS [R01 NS36711-09]; Italian Telethon [GTF04007] FX This study was supported by the Bumpus Foundation, and PHS grant R01 NS36711-09 'Genetic Linkage Study in PD'. The DNA samples contributed by the Parkinson Institute - Istituti Clinici di Perfezionamento, Milan, Italy, were from the 'Human genetic bank of patients affected by PD and Parkinsonisms', supported by Italian Telethon grant n. GTF04007. NR 15 TC 46 Z9 46 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD NOV 5 PY 2008 VL 6 AR 32 DI 10.1186/1741-7015-6-32 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 382MX UT WOS:000261611200001 PM 18986508 ER PT J AU Woody, GE Poole, SA Subramaniam, G Dugosh, K Bogenschutz, M Abbott, P Patkar, A Publicker, M McCain, K Potter, JS Forman, R Vetter, V McNicholas, L Blaine, J Lynch, KG Fudala, P AF Woody, George E. Poole, Sabrina A. Subramaniam, Geetha Dugosh, Karen Bogenschutz, Michael Abbott, Patrick Patkar, Ashwin Publicker, Mark McCain, Karen Potter, Jennifer Sharpe Forman, Robert Vetter, Victoria McNicholas, Laura Blaine, Jack Lynch, Kevin G. Fudala, Paul TI Extended vs Short-term Buprenorphine-Naloxone for Treatment of Opioid-Addicted Youth A Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID METHADONE-MAINTENANCE TREATMENT; DRUG-USERS; DEPENDENCE; ABUSE; PHARMACOLOGY; NALTREXONE; INJECTION; RELAPSE AB Context The usual treatment for opioid- addicted youth is detoxification and counseling. Extended medication- assisted therapy may be more helpful. Objective To evaluate the efficacy of continuing buprenorphine- naloxone for 12 weeks vs detoxification for opioid- addicted youth. Design, Setting, and Patients Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine- naloxone or a 14- day taper (detox). Interventions Patients in the 12- week buprenorphine- naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Main Outcome Measure Opioid- positive urine test result at weeks 4, 8, and 12. Results The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioidpositive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P =. 09). At week 4, 59 detox patients had positive results ( 61%; 95% confidence interval [CI]= 47%-75%) vs 58 12- week buprenorphine- naloxone patients (26%; 95% CI= 14%- 38%). At week 8, 53 detox patients had positive results ( 54%; 95% CI= 38%- 70%) vs 52 12- week buprenorphine- naloxone patients ( 23%; 95% CI= 11%- 35%). At week 12, 53 detox patients had positive results (51%; 95% CI= 35%- 67%) vs 49 12- week buprenorphine-naloxone patients (43%; 95% CI= 29%-57%). By week 12, 16 of 78 detox patients ( 20.5%) remained in treatment vs 52 of 74 12- week buprenorphine-naloxone patients ( 70%; chi(2)(1) = 32.90, P <. 001). During weeks 1 through 12, patients in the 12- week buprenorphine- naloxone group reported less opioid use (chi(2)(1) = 18.45, P <. 001), less injecting (chi(2)(1) = 6.00, P =. 01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P <. 001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12. Conclusions Continuing treatment with buprenorphine- naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer- term treatment with buprenorphine for young individuals with opioid dependence. Trial Registration clinicaltrials. gov Identifier: NCT00078130. C1 [Woody, George E.; Poole, Sabrina A.; Dugosh, Karen; Forman, Robert; McNicholas, Laura; Lynch, Kevin G.; Fudala, Paul] Univ Penn, Dept Psychiat, Treatment Res Inst, Philadelphia, PA 19106 USA. [Subramaniam, Geetha] Johns Hopkins Univ, Div Child & Adolescent Psychiat, Baltimore, MD USA. [Bogenschutz, Michael; Abbott, Patrick] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Bogenschutz, Michael] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA. [Abbott, Patrick] Univ New Mexico, Hlth Sci Ctr, Addict Program, Albuquerque, NM 87131 USA. [Abbott, Patrick] Univ New Mexico, Hlth Sci Ctr, Substance Abuse Program, Albuquerque, NM 87131 USA. [Patkar, Ashwin] Duke Univ, Med Ctr, Durham, NC USA. [Publicker, Mark] Mercy Recovery Ctr, Westbrook, ME USA. [McCain, Karen] Duke Univ, Duke Addict Program, Durham, NC USA. [Potter, Jennifer Sharpe] Harvard Univ, Sch Med, Boston, MA USA. [Potter, Jennifer Sharpe] McLean Hosp, Belmont, MA 02178 USA. [Vetter, Victoria] Childrens Hosp Philadelphia, Div Pediat Cardiol, Philadelphia, PA 19104 USA. [Woody, George E.; McNicholas, Laura; Fudala, Paul] Vet Affairs Med Ctr, Philadelphia, PA USA. [Blaine, Jack] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA. RP Woody, GE (reprint author), Univ Penn, Dept Psychiat, Treatment Res Inst, 150 S Independence Mall W,Ste 600, Philadelphia, PA 19106 USA. EM woody@tresearch.org RI Potter, Jennifer/C-6720-2008 OI Potter, Jennifer/0000-0002-7250-4422 FU National Institute on Drug Abuse [U10-DA013711, U10-DA015831, U10-DA13034, K12-DA000357, U10-DA1533, U10DA13043, KO5-DA17009] FX This study was supported by the following grants from the National Institute on Drug Abuse: U10-DA013711 to Duke University (Dr Patkar); U10-DA015831 to Harvard University (Dr Weiss); U10-DA13034 to Johns Hopkins University (Dr Stitzer); K12-DA000357 (Dr Subramaniam); U10-DA1533 to the University of New Mexico (Dr Miller); and U10DA13043 and KO5-DA17009 (Dr Woody). Reckitt Benckiser provided medication for the study. NR 35 TC 138 Z9 139 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 5 PY 2008 VL 300 IS 17 BP 2003 EP 2011 DI 10.1001/jama.2008.574 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 368EX UT WOS:000260605400020 PM 18984887 ER PT J AU Rosenfield, K Jaff, MR AF Rosenfield, Kenneth Jaff, Michael R. TI An 82-Year-Old Woman With Worsening Hypertension Review of Renal Artery Stenosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MAGNETIC-RESONANCE ANGIOGRAPHY; ATHEROSCLEROTIC RENOVASCULAR DISEASE; UNSUCCESSFUL BALLOON ANGIOPLASTY; STENT PLACEMENT; BLOOD-PRESSURE; ISCHEMIC NEPHROPATHY; NATURAL-HISTORY; FOLLOW-UP; MANAGEMENT; TRIAL AB Renal artery stenosis ( RAS) is a common disorder in adults with atherosclerosis and is associated with hypertension, impaired renal function, congestive heart failure, and angina pectoris. The incidence of RAS is increasing because of the aging of the US population and increasing prevalence of atherosclerosis. The case of Mrs S, an 82- year-old woman with long- standing hypertension and unilateral RAS detected by magnetic resonance angiography, illustrates the challenges surrounding indications for revascularization. The discussion reviews the clinical presentation and natural history of RAS and strategies for diagnosis. The role of medical therapy, surgery, and endovascular therapy are reviewed, particularly in the context of guidelines and systematic reviews to help clinicians and patients facing this challenging decision. C1 [Rosenfield, Kenneth] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rosenfield, Kenneth; Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Rosenfield, K (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM krosenfield@fastmail.us FU Sidney R. Rabb Charitable Trust; Sidney and Esther Rabb Charitable Foundation FX This Clinical Crossroads was made possible by a grant from the Sidney R. Rabb Charitable Trust and the Sidney and Esther Rabb Charitable Foundation. NR 53 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 5 PY 2008 VL 300 IS 17 BP 2036 EP 2044 DI 10.1001/jama.300.13.jrr80009 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 368EX UT WOS:000260605400024 PM 18827196 ER PT J AU Zauber, AG Lansdorp-Vogelaar, I Knudsen, AB Wilschut, J van Ballegooijen, M Kuntz, KM AF Zauber, Ann G. Lansdorp-Vogelaar, Iris Knudsen, Amy B. Wilschut, Janneke van Ballegooijen, Marjolein Kuntz, Karen M. TI Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the US Preventive Services Task Force SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID FECAL-OCCULT-BLOOD; LARGE-INTESTINE; LARGE-BOWEL; CLINICAL GUIDELINES; COST-EFFECTIVENESS; UNITED-STATES; POLYPS; COLONOSCOPY; AUTOPSY; SURVEILLANCE AB Background: The U. S. Preventive Services Task Force requested a decision analysis to inform their update of recommendations for colorectal cancer screening. Objective: To assess life-years gained and colonoscopy requirements for colorectal cancer screening strategies and identify a set of recommendable screening strategies. Design: Decision analysis using 2 colorectal cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network. Data Sources: Derived from the literature. Target Population: U. S. average-risk 40-year-old population. Perspective: Societal. Time Horizon: Lifetime. Interventions: Fecal occult blood tests (FOBTs), flexible sigmoidoscopy, or colonoscopy screening beginning at age 40, 50, or 60 years and stopping at age 75 or 85 years, with screening intervals of 1, 2, or 3 years for FOBT and 5, 10, or 20 years for sigmoidoscopy and colonoscopy. Outcome Measures: Number of life-years gained compared with no screening and number of colonoscopies and noncolonoscopy tests required. Results of Base-Case Analysis: Beginning screening at age 50 years was consistently better than at age 60. Decreasing the stop age from 85 to 75 years decreased life-years gained by 1% to 4%, whereas colonoscopy use decreased by 4% to 15%. Assuming equally high adherence, 4 strategies provided similar life-years gained: colonoscopy every 10 years, annual Hemoccult SENSA (Beckman Coulter, Fullerton, California) testing or fecal immunochemical testing, and sigmoidoscopy every 5 years with midinterval Hemoccult SENSA testing. Annual Hemoccult II and flexible sigmoidoscopy every 5 years alone were less effective. Results of Sensitivity Analysis: The results were most sensitive to beginning screening at age 40 years. Limitation: The stop age for screening was based only on chronologic age. Conclusion: The findings support colorectal cancer screening with the following: colonoscopy every 10 years, annual screening with a sensitive FOBT, or flexible sigmoidoscopy every 5 years with a midinterval sensitive FOBT from age 50 to 75 years. C1 [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. Erasmus MC, Rotterdam, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Minneapolis, MN USA. RP Zauber, AG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63rd St, New York, NY 10065 USA. EM zaubera@mskcc.org FU National Cancer Institute [U01-CA-088204, U01-CA-097426, U01-CA-115953]; Agency for Healthcare Research and Quality [HHSP233200700350P, HHSP233200700210P, HHSP233200700196P] FX By the National Cancer Institute (U01-CA-088204, U01-CA-097426, and U01-CA-115953) and the Agency for Healthcare Research and Quality (HHSP233200700350P, HHSP233200700210P, and HHSP233200700196P). NR 40 TC 312 Z9 315 U1 1 U2 12 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 4 PY 2008 VL 149 IS 9 BP 659 EP + PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 367XK UT WOS:000260585700006 PM 18838717 ER PT J AU Lee, MH Klein, RL El-Shewy, HM Luttrell, DK Luttrell, LM AF Lee, Mi-Hye Klein, Richard L. El-Shewy, Hesham M. Luttrell, Deirdre K. Luttrell, Louis M. TI The Adiponectin Receptors AdipoR1 and AdipoR2 Activate ERK1/2 through a Src/Ras-Dependent Pathway and Stimulate Cell Growth SO BIOCHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; COMPLEMENT-RELATED PROTEIN; FATTY-ACID OXIDATION; ENDOTHELIAL-CELLS; INSULIN-RESISTANCE; NITRIC-OXIDE; MAP KINASE; KAPPA-B; ACRP30/ADIPONECTIN; ACRP30 AB Adiponectin is an adipocyte-derived cytokine that has attracted much attention because of its insulin-sensitizing effects in liver and skeletal muscle. Two adiponectin receptors, AdipoR1/R2, have been cloned, but relatively little is known about their intracellular signaling mechanisms. We found that full-length adiponectin rapidly and robustly activates the ERK1/2 mitogen-activated protein kinase pathway in primary vascular smooth muscle, vascular endothelial cells, and hepatocytes. In a HEK293 cell model, we found that downregulating AdipoR1/R2 simultaneously, but not individually, by RNA interference attenuated adiponectin-induced ERK1/2 activation, suggesting that either receptor was sufficient to mediate the response. Downregulation of T-cadherin, another adiponectin binding protein, enhanced. the response. Downregulation of APPL1, an adapter protein and putative mediator of AdipoR1/R2 signaling, impaired adiponectin-stimulated ERK1/2 activation. Inhibiting PKA modestly attenutated ERK1/2 activation, while inhibition of Src family tyrosine kinases with PP2 abolished the response. The small GTPase inhibitor Clostridium difficile toxin B also produced complete inhibition. Adiponectin caused rapid, PP2-sensitive activation of Ras, but not the cAMP-regulated small GTPase, Rap1, suggesting that Src-dependent Ras activation is the dominant mechanism of adiponectin-stimulated ERK1/2 activation. To test whether Ras-ERK1/2 signaling by adiponectin was physiologically relevant, we determined the effects of overexpressing AdipoR1, adiponectin, or both on the rate of HEK293 cell growth. Overexpression of adiponectin alone, but not AdipoR1 alone, supported growth under serum-free conditions, while simultaneous expression of both led to further enhancement. These results suggest that adiponectin can exert proliferative effects by activating Ras signaling pathways. C1 [Lee, Mi-Hye; Klein, Richard L.; El-Shewy, Hesham M.; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Lee, Mi-Hye; Klein, Richard L.; El-Shewy, Hesham M.; Luttrell, Deirdre K.; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Klein, Richard L.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St 816 CSB,MSC6ZY, Charleston, SC 29425 USA. EM luttrell@musc.edu FU National Institutes of Health [DK58283]; Department of Veterans Affairs Merit; Research Enhancement Award Program FX This work was supported by National Institutes of Health Grant DK58283 (L.M.L.) and Department of Veterans Affairs Merit (R.L.K.) and Research Enhancement Award Program (L.M.L.) awards. NR 39 TC 63 Z9 66 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 4 PY 2008 VL 47 IS 44 BP 11682 EP 11692 DI 10.1021/bi801451f PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366TU UT WOS:000260507100033 PM 18842004 ER PT J AU Krivtsov, AV Feng, Z Lemieux, ME Faber, J Vempati, S Sinha, AU Xia, X Jesneck, J Bracken, AP Silverman, LB Kutok, JL Kung, AL Armstrong, SA AF Krivtsov, Andrei V. Feng, Zhaohui Lemieux, Madeleine E. Faber, Joerg Vempati, Sridhar Sinha, Amit U. Xia, Xiaobo Jesneck, Jonathan Bracken, Adrian P. Silverman, Lewis B. Kutok, Jeffery L. Kung, Andrew L. Armstrong, Scott A. TI H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias SO CANCER CELL LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION; TRANSCRIPTIONAL ELONGATION; MLL TRANSLOCATIONS; CHROMATIN; METHYLTRANSFERASE; MODEL; CLASSIFICATION; TARGETS; ROLES AB We created a mouse model wherein conditional expression of an MII-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with MII-AF4-associated gene expression profiles in murine ALLs and in human MLL-rearranged leukemias. Human MLL-rearranged ALLs could be distinguished from other ALLs. by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression. C1 [Krivtsov, Andrei V.; Feng, Zhaohui; Faber, Joerg; Vempati, Sridhar; Sinha, Amit U.; Silverman, Lewis B.; Kung, Andrew L.; Armstrong, Scott A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Lemieux, Madeleine E.; Vempati, Sridhar; Sinha, Amit U.; Xia, Xiaobo; Jesneck, Jonathan; Silverman, Lewis B.; Kung, Andrew L.; Armstrong, Scott A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kutok, Jeffery L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bracken, Adrian P.] Univ Dublin Trinity Coll, Dept Genet, Smurfit Inst, Dublin 2, Ireland. RP Armstrong, SA (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM scott.armstrong@childrens.harvard.edu RI Faber, Joerg/G-4549-2010; OI Krivtsov, Andrei/0000-0002-5511-1686; Lemieux, Madeleine/0000-0001-6355-8691; Kung, Andrew/0000-0002-9091-488X FU National Cancer Institute [K08CA92551, 5U01 CA105423, 5P01CA0684841]; Leukemia & Lymphoma Society, and the Damon Runyon Cancer Research Foundation FX We would like to thank Y. Fujiwara for help with embryonic stem cell modification and blastocyst injections. This work was supported in part by the National Cancer Institute (grants K08CA92551, 5U01 CA105423, and 5P01CA068484 1), the Leukemia & Lymphoma Society, and the Damon Runyon Cancer Research Foundation. NR 38 TC 263 Z9 268 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV 4 PY 2008 VL 14 IS 5 BP 355 EP 368 DI 10.1016/j.ccr.2008.10.001 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 369OC UT WOS:000260702800005 PM 18977325 ER PT J AU Wurdinger, T Tannous, BA Saydam, O Skog, J Grau, S Soutschek, J Weissleder, R Breakefield, XO Krichevsky, AM AF Wuerdinger, Thomas Tannous, Bakhos A. Saydam, Okay Skog, Johan Grau, Stephan Soutschek, Juergen Weissleder, Ralph Breakefield, Xandra O. Krichevsky, Anna M. TI miR-296 Regulates Growth Factor Receptor Overexpression in Angiogenic Endothelial Cells SO CANCER CELL LA English DT Article ID GENE-EXPRESSION; OCULAR NEOVASCULARIZATION; TUMOR ANGIOGENESIS; VASCULAR INTEGRITY; IN-VIVO; MICRORNAS; DEGRADATION; TARGETS; CANCER; THERAPY AB A key step in angiogenesis is the upregulation of growth factor receptors on endothelial cells. Here, we demonstrate that a small regulatory microRNA, miR-296, has a major role in this process. Glioma cells and angiogenic growth factors elevate the level of miR-296 in primary human brain microvascular endothelial cells in culture. The miR-296 level is also elevated in primary tumor endothelial cells isolated from human brain tumors compared to normal brain endothelial cells. Growth factor-induced miR-296 contributes significantly to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) mRNA, leading to decreased levels of HGS and thereby reducing HGS-mediated degradation of the growth factor receptors VEGFR2 and PDGFR beta. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo. C1 [Wuerdinger, Thomas; Tannous, Bakhos A.; Saydam, Okay; Skog, Johan; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Wuerdinger, Thomas; Tannous, Bakhos A.; Weissleder, Ralph; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Ctr Mol Imaging Res, Boston, MA 02115 USA. [Wuerdinger, Thomas; Tannous, Bakhos A.; Saydam, Okay; Skog, Johan; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Krichevsky, Anna M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Wuerdinger, Thomas] Canc Ctr Amsterdam, VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1007 MB Amsterdam, Netherlands. [Grau, Stephan] Univ Munich, Klinikum Grosshadern, Dept Neurosurg, D-80539 Munich, Germany. [Soutschek, Juergen] Regulus Therapeut, Carlsbad, CA 92008 USA. RP Breakefield, XO (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. EM breakefield@hms.harvard.edu FU American Brain Tumor Association; NIH [NCI P50 CA86355-04, NCI P01 CA69246, NINDS P30NS045776]; Brain Tumor Society FX We would like to acknowledge the Steve Kaplan Fellowship from the American Brain Tumor Association (T.W.) NIH grants NCI P50 CA86355-04 (R.W. and X.O.B.), NCI P01 CA69246 (X.O.B.), and NINDS P30NS045776 (X.O.B.); and the Brain Tumor Society (A.M.K.). We thank E. Erkan, L. Wedekind. and P. Waterman for technical assistance and G.S. Mack for critical reading of the manuscript. NR 46 TC 225 Z9 239 U1 3 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV 4 PY 2008 VL 14 IS 5 BP 382 EP 393 DI 10.1016/j.ccr.2008.10.005 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 369OC UT WOS:000260702800007 PM 18977327 ER PT J AU An, J Mo, D Liu, H Veena, MS Srivatsan, ES Massoumi, R Rettig, MB AF An, Jiabin Mo, Deqiong Liu, Huiren Veena, Mysore S. Srivatsan, Eri S. Massoumi, Ramin Rettig, Matthew B. TI Inactivation of the CYLD Deubiquitinase by HPV E6 Mediates Hypoxia-Induced NF-kappa B Activation SO CANCER CELL LA English DT Article ID HUMAN-PAPILLOMAVIRUS TYPE-16; GENE-EXPRESSION; ASPARAGINYL HYDROXYLASE; TUMOR MICROENVIRONMENT; EPITHELIAL-CELLS; INDUCIBLE FACTOR; CERVICAL-CANCER; KINASE PATHWAYS; P53; PROTEIN AB The biochemical mechanisms that underlie hypoxia-induced NF-kappa B activity have remained largely undefined. Here, we find that prolonged hypoxia-induced NF-kappa B activation is restricted to cancer cell lines infected with high-risk human papillomavirus (HPV) serotypes. The HPV-encoded E6 protein is necessary and sufficient for prolonged hypoxia-induced NF-kappa B activation in these systems. The molecular target of E6 in the NF-kappa B pathway is the CYLD lysine 63 (K63) deubiquitinase, a negative regulator of the NF-kappa B pathway. Specifically, hypoxia stimulates E6-mediated ubiquitination and proteasomal degradation of CYLD. Given the established role of NF-kappa B in human carcinogenesis, these findings provide a potential molecular/viral link between hypoxia and the adverse clinical outcomes observed in HPV-associated malignancies. C1 [An, Jiabin; Mo, Deqiong; Liu, Huiren; Rettig, Matthew B.] VA Greater Los Angeles Healthcare Syst W Los Ange, Dept Med, Los Angeles, CA 90095 USA. [Veena, Mysore S.; Srivatsan, Eri S.] VA Greater Los Angeles Healthcare Syst W Los Ange, Dept Surg, Los Angeles, CA 90095 USA. [Massoumi, Ramin] Lund Univ, Malmo Univ Hosp, Dept Lab Med Cell & Expt Pathol, SE-20502 Malmo, Sweden. [Rettig, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Rettig, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. RP Rettig, MB (reprint author), VA Greater Los Angeles Healthcare Syst W Los Ange, Dept Med, Los Angeles, CA 90095 USA. EM mrettig@mednet.ucla.edu OI Massoumi, Ramin/0000-0001-8875-6440 FU NIH and the US Department of Veterans Affairs; NIH [2P30DK041301] FX This work was supported by the NIH and the US Department of Veterans Affairs (to M.B.R.). We thank C. Logg and N. Kasahara (UCLA) for helpful advice, the UCLA Vector Core (NIH grant 2P30DK041301) for production of viral vectors, and G. Cheng and A. Lichtenstein for helpful NR 53 TC 52 Z9 56 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV 4 PY 2008 VL 14 IS 5 BP 394 EP 407 DI 10.1016/j.ccr.2008.10.007 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 369OC UT WOS:000260702800008 PM 18977328 ER PT J AU Wu, JY Purton, LE Rodda, SJ Chen, M Weinstein, LS McMahon, AP Scadden, DT Kronenberg, HM AF Wu, Joy Y. Purton, Louise E. Rodda, Stephen J. Chen, Min Weinstein, Lee S. McMahon, Andrew P. Scadden, David T. Kronenberg, Henry M. TI Osteoblastic regulation of B lymphopoiesis is mediated by G(s)alpha-dependent signaling pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE B lymphocyte; G protein; osteoblast ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW; PARATHYROID-HORMONE; DIFFERENTIATION; RECEPTOR; MICE; NICHES; MOUSE; MAINTENANCE; DEFICIENCY AB Osteoblasts play an increasingly recognized role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that heterotrimeric G protein a subunit G(s)alpha is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of G(s)alpha early in the osteoblast lineage results in a 59% decrease in the percentage of B cell precursors in the bone marrow. Analysis of peripheral blood from mutant mice revealed a 67% decrease in the number of circulating B lymphocytes by 10 days age. Strikingly, other mature hematopoietic lineages are not decreased significantly. Mice lacking Gsa in cells of the lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in G(s)alpha-deficient blasts, and exogenous IL-7 is able to restore B cell populations in the bone marrow of mutant mice. Finally, the in B lymphopoiesis can be rescued by transplantation into a microenvironment. These findings confirm that osteoblasts are an important component of the B lymphocyte niche and demonstrate in vivo that G(s)alpha-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner. C1 [Wu, Joy Y.; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Purton, Louise E.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Purton, Louise E.; McMahon, Andrew P.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Rodda, Stephen J.; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. [Chen, Min; Weinstein, Lee S.] NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hkronenberg@partners.org FU National Institutes of Health [AR053781, DK071773, HL081030, DK117940, DK056246]; National Institute of Diabetes and Digestive and Kidney Diseases' Intramural Research Program; National Health and Medical Research Council of Australia [301299]; Arthritis Foundation [401683] FX We thank Drs. Sean Wu, Carl Walkley, and Heather Fleming for discussion and helpful suggestions; Dr. Natalie Sims for quantitation of osteoblast surfaces; David Dombkowski and Laura Prickett for assistance with FACS sorting; James Oh for technical assistance; and the MGH Center for Comparative Medicine staff for caring for the mice in this study. This work was supported in part by National Institutes of Health Grants AR053781 (to J.Y.W.), DK071773 (to L.E.P.), HL081030 (to H.M.K. and D.T.S.), DK117940 (to H.M.K.), and DK056246 (to A.P.M.), and by the National Institute of Diabetes and Digestive and Kidney Diseases' Intramural Research Program (M.C. and L.S.W.). S.R. was supported by postdoctoral fellowships from the National Health and Medical Research Council of Australia (301299) and the Arthritis Foundation (401683). NR 42 TC 93 Z9 95 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 4 PY 2008 VL 105 IS 44 BP 16976 EP 16981 DI 10.1073/pnas.0802898105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PP UT WOS:000260913800034 PM 18957542 ER PT J AU Vicente, R Gollo, LL Mirasso, CR Fischer, I Pipa, G AF Vicente, Raul Gollo, Leonardo L. Mirasso, Claudio R. Fischer, Ingo Pipa, Gordon TI Dynamical relaying can yield zero time lag neuronal synchrony despite long conduction delays SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thalamocortical system; isochronous oscillations; phase locking; long-range synchronization; axonal latency ID CAT VISUAL-CORTEX; OSCILLATORY RESPONSES; NEOCORTICAL NEURONS; NEURAL SYNCHRONY; CORTICAL AREAS; COHERENCE; NETWORKS; COMMUNICATION; INTEGRATION; MECHANISM AB Multielectrode recordings have revealed zero time lag synchronization among remote cerebral cortical areas. However, the axonal conduction delays among such distant regions can amount to several tens of milliseconds. It is still unclear which mechanism is giving rise to isochronous discharge of widely distributed neurons, despite such latencies. Here, we investigate the synchronization properties of a simple network motif and found that, even in the presence of large axonal conduction delays, distant neuronal populations self-organize into lag-free oscillations. According to our results, cortico-cortical association fibers and certain cortico-thalamo-cortical loops represent ideal circuits to circumvent the phase shifts and time lags associated with conduction delays. C1 [Vicente, Raul; Pipa, Gordon] Max Planck Inst Brain Res, Dept Neurophysiol, D-60528 Frankfurt, Germany. [Vicente, Raul; Pipa, Gordon] Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany. [Gollo, Leonardo L.; Mirasso, Claudio R.] Univ Isl Baleares, CSIC, Inst Fis Interdisciplinar & Sistemas Complejos, E-07122 Palma de Mallorca, Spain. [Fischer, Ingo] Heriot Watt Univ, Sch Engn & Phys Sci, Edinburgh EH14 4AS, Midlothian, Scotland. [Fischer, Ingo] Heriot Watt Univ, Joint Res Inst Integrated Syst, Edinburgh EH14 4AS, Midlothian, Scotland. [Pipa, Gordon] MIT, Dept Brain & Cognit Sci, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA. [Pipa, Gordon] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Vicente, R (reprint author), Max Planck Inst Brain Res, Dept Neurophysiol, Deutschordenstr 46, D-60528 Frankfurt, Germany. EM raulvicente@mpih-frankfurt.mpg.de RI Vicente, Raul/E-1566-2011; Mirasso, Claudio/B-8661-2008; Fischer, Ingo/C-2843-2011; Gollo, Leonardo/K-6971-2014; Pipa, Gordon/M-1813-2014 OI Vicente, Raul/0000-0002-2497-0007; Fischer, Ingo/0000-0003-1881-9842; Gollo, Leonardo/0000-0003-3505-9259; Pipa, Gordon/0000-0002-3416-2652 FU Her-tie Foundation; European Commission [043309]; Spanish MCyT and Feder [FIS-2004-00953] FX We thank Wolf Singer, Christopher J. Honey, and Nancy Kopell for the careful reading of the manuscript and helpful discussions. R. V. and G. P. also thank Carl van Vreeswijk and Victor Eguiluz for fruitful discussions. This work was supported by the Her-tie Foundation, European Commission Project GABA (FP6-NEST Contract 043309), and the Spanish MCyT and Feder under Project FISICO (FIS-2004-00953). NR 49 TC 144 Z9 145 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 4 PY 2008 VL 105 IS 44 BP 17157 EP 17162 DI 10.1073/pnas.0809353105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PP UT WOS:000260913800065 PM 18957544 ER PT J AU Coste, A Louet, JF Lagouge, M Lerin, C Antal, MC Meziane, H Schoonjans, K Puigserver, P O'Malley, BW Auwerx, J AF Coste, Agnes Louet, Jean-Francois Lagouge, Marie Lerin, Carles Antal, Maria Cristina Meziane, Hamid Schoonjans, Kristina Puigserver, Pere O'Malley, Bert W. Auwerx, Johan TI The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1 alpha SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acetyltransferase; caloric restriction; cofactors; deacetylase; SIRT1 ID STEROID-RECEPTOR COACTIVATOR-3; TRANSCRIPTIONAL COACTIVATORS; ENERGY-BALANCE; METABOLISM; HOMEOSTASIS; RESISTANCE; COMPLEX; FAMILY; SIRT1; WHITE AB Transcriptional control of metabolic circuits requires coordination between specific transcription factors and coregulators and is often deregulated in metabolic diseases. We characterized here the mechanisms through which the coactivator SRC-3 controls energy homeostasis. SRC-3 knock-out mice present a more favorable metabolic profile relative to their wild-type littermates. This metabolic improvement in SRC-3(-/-) mice is caused by an increase in mitochondrial function and in energy expenditure as a consequence of activation of PGC-1 alpha. By controlling the expression of the only characterized PGC-1 alpha acetyltransf erase GCN5, SRC-3 induces PGC-1 alpha acetylation and consequently inhibits its activity. Interestingly, SRC-3 expression is induced by caloric excess, resulting in the inhibition of PGC-1 alpha activity and energy expenditure, whereas caloric restriction reduces SRC-3 levels leading to enhanced PGC-1 alpha activity and energy expenditure. Collectively, these data suggest that SRC-3 is a critical link in a cofactor network that uses PGC-1 alpha as an effector to control mitochondrial function and energy homeostasis. C1 [Coste, Agnes; Lagouge, Marie; Schoonjans, Kristina; Auwerx, Johan] Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. [Louet, Jean-Francois; O'Malley, Bert W.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Lerin, Carles; Puigserver, Pere; Auwerx, Johan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lerin, Carles; Puigserver, Pere; Auwerx, Johan] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Antal, Maria Cristina; Meziane, Hamid; Auwerx, Johan] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France. [Schoonjans, Kristina] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. RP Auwerx, J (reprint author), Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. EM berto@bcm.tmc.edu; johan.auwerx@epfl.ch OI Louet, Jean-Francois/0000-0002-1626-7098 FU CNRS; INSERM; Hopitaux Universitaires de Strasbourg; EU [QLRT-2001-00930, LSHM-CT-2004-512013]; NIH [DK59820, HD07857]; Nestle FX The authors thank Aurelie Auburtin, Adeline Jauffre, Nadia Messaddeq, Marie-France Champy, Jerome Feige, Carles Canto, and Charles Foulds for helpful discussions and technical assistance. This work was supported by grants from CNRS, INSERM, Hopitaux Universitaires de Strasbourg, EU (QLRT-2001-00930 and LSHM-CT-2004-512013), and NIH (DK59820 and HD07857). ML was supported by Nestle. NR 25 TC 107 Z9 115 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 4 PY 2008 VL 105 IS 44 BP 17187 EP 17192 DI 10.1073/pnas.0808207105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PP UT WOS:000260913800070 PM 18957541 ER PT J AU Dougherty, DD Kong, J Webb, M Bonab, AA Fischman, AJ Gollub, RL AF Dougherty, Darin D. Kong, Jian Webb, Megan Bonab, Ali A. Fischman, Alan J. Gollub, Randy L. TI A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE acupuncture; placebo; analgesia; opioid; PET; fMRI; 11C-diprenorphine ID POSITRON-EMISSION-TOMOGRAPHY; OPIOID RECEPTOR-BINDING; VERBAL PAIN DESCRIPTORS; ELECTRICAL-STIMULATION; PLACEBO NEEDLE; HUMAN BRAIN; ELECTROACUPUNCTURE STIMULATION; ACUPOINT STIMULATION; RHEUMATOID-ARTHRITIS; PERIAQUEDUCTAL GRAY AB Functional neuroimaging Studies Suggest that a lateral network in the brain is associated with the Sensory aspects of pain perception while a medial network is associated with affective aspects. The highest concentration of opioid receptors is in the medial network. There is significant evidence that endogenous opioids are central to the experience of pain and analgesia. We applied an integrative multimodal imaging approach during acupuncture. We found functional magnetic resonance imaging signal changes in the orbitofrontal cortex, insula, and pons and [11C]diprenorphine positron emission tomography signal changes in the orbitofrontal cortex, medial prefrontal cortex, insula, thalamus, and anterior cingulate cortex. These findings include brain regions within both the lateral and medial pain networks. (C) 2008 Elsevier B.V. All rights reserved. C1 [Dougherty, Darin D.; Kong, Jian; Webb, Megan; Gollub, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program,Dept Psychiat, Charlestown, MA 02129 USA. [Dougherty, Darin D.; Kong, Jian; Gollub, Randy L.] Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. [Dougherty, Darin D.; Kong, Jian; Gollub, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Bonab, Ali A.; Fischman, Alan J.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. RP Dougherty, DD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program,Dept Psychiat, CNY 2612,Bldg 149,13th St, Charlestown, MA 02129 USA. EM ddougherty@partners.org OI Gollub, Randy L./0000-0002-9434-4044 FU NIH (NCCAM) [R21AT00949, R21AT 001922]; Mallinckrodt General Clinical Research Center Biomedical Imaging Core [PO1-AT002048, KO1AT003883, M01-RR-001066]; Center for Functional Neuroimaging Technologies [P41RR14075]; NCRR; MIND Institute FX Funding for this study came from: NIH (NCCAM) R21AT00949 and R21AT 001922 to Randy Gollub, PO1-AT002048 to Bruce Rosen/Randy Gollub, KO1AT003883 to Jian Kong, M01-RR-001066 for Mallinckrodt General Clinical Research Center Biomedical Imaging Core, P41RR14075 for Center for Functional Neuroimaging Technologies from NCRR and the MIND Institute. NR 48 TC 43 Z9 50 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 3 PY 2008 VL 193 IS 1 BP 63 EP 68 DI 10.1016/j.bbr.2008.04.020 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 341TQ UT WOS:000258738400007 PM 18562019 ER PT J AU Kuo, F Subramanian, B Kotyla, T Wilson, TA Yoganathan, S Nicolosi, RJ AF Kuo, Fonghsu Subramanian, Balajikarthick Kotyla, Timothy Wilson, Thomas A. Yoganathan, Subbiah Nicolosi, Robert J. TI Nanoemulsions of an anti-oxidant synergy formulation containing gamma tocopherol have enhanced bioavailability and anti-inflammatory properties SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE MicroFluidizer Processor (R)-based nanoemulsions; Anti-oxidant synergy formulation; Croton oil; Tocopherol ID DRUG-DELIVERY SYSTEMS; ALPHA-TOCOPHEROL; VITAMIN-E; TRANSDERMAL DELIVERY; PARTICLE-SIZE; EMU OIL; INFLAMMATION; PACLITAXEL; INCREASES; EMULSION AB The present study investigated whether MicroFluidizer Processor (R)-based nanoemulsions of an antioxidant synergy formulation (ASF), containing delta, alpha and gamma tocopherol influenced inflammation and bioavailability in CD-1 mice. Croton oil was applied to all animals' right ear lobe to induce inflammation. Auricular thickness was measured after 2 and 6 h after the various treatments. The animal plasma and ear lobes were collected and frozen for bioavailability and cytokine analyses. The ASF nanoemulsions of alpha,delta, orgamma tocopherol significantly reduced auricular thickness compared to control (57, -57, and -71%, respectively) and blank nanoemulsion (-50, -50, -67%, respectively). Relative to the suspensions of ASF, only the nanoemulsion of ASF containing gamma tocopherol significantly reduced auricular thickness (-60%). whereas the 40% reduction with nanoemulsions of delta tocopherol compared to suspension was not statistically significant. Auricular concentrations of cytokines TNF-alpha and IL-1 alpha were significantly reduced in mice treated only with ASF nanoemulsions of gamma tocopherol compared to control (-53, -46%, respectively) and blank nanoemulsion (-52, -46%, respectively). Auricular thickness was significantly associated with tissue TNF-alpha (r=0.539, p < 0.001) and IL-1 alpha concentrations (r=0.404, p=0.01). Bioavailability for gamma and delta was dramatically enhanced (2.2- and 2.4-folds) with the nanoemulsion compared to suspensions. Only the plasma gamma tocopherol concentration was significantly associated with auricular thickness (r=-0.643, P=0.001). In conclusion, nanoemulsions of ASF containing gamma, alpha, and delta tocopherol, have enhanced anti-inflammatory properties and increased bioavailability, with gamma tocopherol, in particular compared to their suspensions. (c) 2008 Elsevier B.V. All rights reserved. C1 [Kuo, Fonghsu; Subramanian, Balajikarthick; Kotyla, Timothy; Wilson, Thomas A.; Nicolosi, Robert J.] Univ Massachusetts Lowell, Ctr Hlth & Dis Res, Div NanoMed, Biomed Engn & Biotechnol PhD Program, Lowell, MA 01854 USA. [Yoganathan, Subbiah] Forsyth Inst, Boston, MA 02115 USA. RP Nicolosi, RJ (reprint author), Univ Massachusetts Lowell, Ctr Hlth & Dis Res, Div NanoMed, Biomed Engn & Biotechnol PhD Program, 3 Solomont Way, Lowell, MA 01854 USA. EM nicolosi.robert@yahoo.com OI Wilson, Thomas/0000-0001-8363-4356 FU Microfludics Corp., Newton [MA 02464] FX We acknowledge Animal Facility Manager Sheryl Perry for her technical assistance and Maureen Faul of the Center for Health and Disease Research for her administrative assistance. These studies were partially supported by Microfludics Corp., Newton, MA 02464 NR 41 TC 37 Z9 39 U1 4 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD NOV 3 PY 2008 VL 363 IS 1-2 SI SI BP 206 EP 213 DI 10.1016/j.ijpharm.2008.07.022 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 366KC UT WOS:000260478700026 PM 18718513 ER PT J AU Yang, T Knowles, JK Lu, Q Zhang, H Arancio, O Moore, LA Chang, T Wang, Q Andreasson, K Rajadas, J Fuller, GG Xie, YM Massa, SM Longo, FM AF Yang, Tao Knowles, Juliet K. Lu, Qun Zhang, Hong Arancio, Ottavio Moore, Laura A. Chang, Timothy Wang, Qian Andreasson, Katrin Rajadas, Jayakumar Fuller, Gerald G. Xie, Youmei Massa, Stephen M. Longo, Frank M. TI Small Molecule, Non-Peptide p75(NTR) Ligands Inhibit A beta-Induced Neurodegeneration and Synaptic Impairment SO PLOS ONE LA English DT Article AB The p75 neurotrophin receptor (p75(NTR)) is expressed by neurons particularly vulnerable in Alzheimer's disease (AD). We tested the hypothesis that non-peptide, small molecule p75(NTR) ligands found to promote survival signaling might prevent A beta-induced degeneration and synaptic dysfunction. These ligands inhibited Ab-induced neuritic dystrophy, death of cultured neurons and A beta-induced death of pyramidal neurons in hippocampal slice cultures. Moreover, ligands inhibited A beta-induced activation of molecules involved in AD pathology including calpain/cdk5, GSK3b and c-Jun, and tau phosphorylation, and prevented A beta-induced inactivation of AKT and CREB. Finally, a p75(NTR) ligand blocked A beta-induced hippocampal LTP impairment. These studies support an extensive intersection between p75(NTR) signaling and A beta pathogenic mechanisms, and introduce a class of specific small molecule ligands with the unique ability to block multiple fundamental AD-related signaling pathways, reverse synaptic impairment and inhibit Ab-induced neuronal dystrophy and death. C1 [Yang, Tao; Knowles, Juliet K.; Chang, Timothy; Wang, Qian; Andreasson, Katrin; Rajadas, Jayakumar; Longo, Frank M.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Yang, Tao; Knowles, Juliet K.; Moore, Laura A.; Xie, Youmei; Longo, Frank M.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Lu, Qun] E Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC USA. [Zhang, Hong; Arancio, Ottavio] Columbia Univ, Taub Inst, Dept Pathol, New York, NY 10027 USA. [Rajadas, Jayakumar; Fuller, Gerald G.] Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA. [Massa, Stephen M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Dept Neurol, Lab Computat Neurochem & Drug Discovery, San Francisco, CA USA. RP Yang, T (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. EM longo@stanford.edu FU Institute for the Study of Aging; Alzheimer's Association; Eastern Chapter of the North Carolina Alzheimer's Association; NINDS [F30 NA051971]; NIA [AG026630]; NCI [CA111891, NS049442]; Veterans Administration FX This project was supported by the Institute for the Study of Aging (FL), Alzheimer's Association (FL), the Eastern Chapter of the North Carolina Alzheimer's Association (FL), NINDS F30 NA051971 (JK), NIA AG026630 (QL), NCI CA111891 (QL), NS049442 (OA) and the Veterans Administration (SM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 57 Z9 59 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 3 PY 2008 VL 3 IS 11 AR e3604 DI 10.1371/journal.pone.0003604 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432LI UT WOS:000265134200003 PM 18978948 ER PT J AU Gordon, JA Vozenilek, JA AF Gordon, James A. Vozenilek, John A. CA SAEM Simulation Task Force Technology Med Educ Comm TI 2008 Academic Emergency Medicine Consensus Conference The Science of simulation in healthcare: Defining and developing clinical expertise SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-MEDICINE C1 [Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA USA. [Vozenilek, John A.] Northwestern Univ, Ctr Simulat Technol & Acad Res, Div Emergency Med, Evanston NW Healthcare,NW McGaw Simulat Network, Chicago, IL 60611 USA. [Vozenilek, John A.] Northwestern Univ, Dept Emergency, Feinberg Sch Med, Chicago, IL 60611 USA. [Vozenilek, John A.] Northwestern Univ, Dept Med Educ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgordon3@partners.org OI Vozenilek, John/0000-0001-7955-4089 FU Agency for Healthcare Research and Quality (AHRQ) [1 R13 HS017656-01]; Josiah Macy, Jr. Foundation; Risk Management Foundation of the Harvard Medical Institutions (CRICO/RMF); Association of American Medical Colleges's MedEdPORTAL; Medical Education Technologies, Inc; Laerdal Medical Corp; academic /affiliated institutions FX Funding for this conference was made possible in part by Grant 1 R13 HS017656-01 from the Agency for Healthcare Research and Quality (AHRQ). The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U. S. Government. Additional major funding was provided by the Josiah Macy, Jr. Foundation, the Risk Management Foundation of the Harvard Medical Institutions (CRICO/RMF), the Association of American Medical Colleges's MedEdPORTAL, and unrestricted educational grants from Medical Education Technologies, Inc., Laerdal Medical Corp., and a number of academic /affiliated institutions ( see Appendix B for full listing). NR 4 TC 12 Z9 12 U1 3 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2008 VL 15 IS 11 BP 971 EP 977 DI 10.1111/j.1553-2712.2008.00252.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 374NT UT WOS:000261051700001 ER PT J AU Vozenilek, JA Gordon, JA AF Vozenilek, John A. Gordon, James A. TI Future Directions: A Simulation-based Continuing Medical Education Network in Emergency Medicine SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material DE simulation; continuing medical education; lifelong learning and self-assessment; procedural skills; clinical skills C1 [Vozenilek, John A.] Northwestern Univ, Ctr Simulat Technol & Acad Res, Div Emergency Med, Evanston NW Healthcare,NW McGaw Simulat Network, Chicago, IL 60611 USA. [Vozenilek, John A.] Northwestern Univ, Feinberg Sch Med, Dept Emergency, Chicago, IL 60611 USA. [Vozenilek, John A.] Northwestern Univ, Feinberg Sch Med, Dept Med Educ, Chicago, IL 60611 USA. [Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA USA. [Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Vozenilek, JA (reprint author), Northwestern Univ, Ctr Simulat Technol & Acad Res, Div Emergency Med, Evanston NW Healthcare,NW McGaw Simulat Network, Chicago, IL 60611 USA. EM j-vozenilek@northwestern.edu OI Vozenilek, John/0000-0001-7955-4089 NR 5 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2008 VL 15 IS 11 BP 978 EP 981 DI 10.1111/j.1553-2712.2008.00256.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 374NT UT WOS:000261051700002 PM 19032552 ER PT J AU Rudolph, JW Simon, R Raemer, DB Eppich, WJ AF Rudolph, Jenny W. Simon, Robert Raemer, Daniel B. Eppich, Walter J. TI Debriefing as Formative Assessment: Closing Performance Gaps in Medical Education SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE formative assessment; debriefing; simulation; medical education; formative evalution ID FEEDBACK; STUDENTS; IMPACT AB The authors present a four-step model of debriefing as formative assessment that blends evidence and theory from education research, the social and cognitive sciences, experience drawn from conducting over 3,000 debriefings, and teaching debriefing to approximately 1,000 clinicians worldwide. The steps are to: 1) note salient performance gaps related to predetermined objectives, 2) provide feedback describing the gap, 3) investigate the basis for the gap by exploring the frames and emotions contributing to the current performance level, and 4) help close the performance gap through discussion or targeted instruction about principles and skills relevant to performance. The authors propose that the model, designed for postsimulation debriefings, can also be applied to bedside teaching in the emergency department (ED) and other clinical settings. C1 [Rudolph, Jenny W.; Simon, Robert; Raemer, Daniel B.] Ctr Med Simulat, Cambridge, MA USA. [Rudolph, Jenny W.; Simon, Robert; Raemer, Daniel B.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Rudolph, Jenny W.; Simon, Robert; Raemer, Daniel B.] Harvard Univ, Sch Med, Boston, MA USA. [Eppich, Walter J.] Northwestern Univ, Dept Pediat, Childrens Mem Hosp,Div Emergency Med, KidSTAR Simulat Program,Feinberg Sch Med, Chicago, IL 60611 USA. RP Rudolph, JW (reprint author), Ctr Med Simulat, Cambridge, MA USA. EM jwrudolph@partners.org NR 43 TC 124 Z9 126 U1 6 U2 17 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2008 VL 15 IS 11 BP 1010 EP 1016 DI 10.1111/j.1553-2712.2008.00248.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 374NT UT WOS:000261051700008 PM 18945231 ER PT J AU Spillane, L Hayden, E Fernandez, R Adler, M Beeson, M Goyal, D Smith-Coggins, R Boulet, J AF Spillane, Linda Hayden, Emily Fernandez, Rosemarie Adler, Mark Beeson, Michael Goyal, Deepi Smith-Coggins, Rebecca Boulet, John TI The Assessment of Individual Cognitive Expertise and Clinical Competency: A Research Agenda SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE patient simulation; graduate medical education; competency; medical education ID EMERGENCY-MEDICINE RESIDENTS; HIGH-FIDELITY SIMULATION; PERFORMANCE ASSESSMENTS; STANDARDIZED PATIENTS; AIRWAY MANAGEMENT; CURRICULUM; SKILL; OSCE; CHECKLIST; EDUCATION AB There is a large push to utilize evidence-based practices in medical education. At the same time, credentialing bodies are evaluating the use of simulation technologies to assess the competency and safety of its practitioners. At the 2008 Academic Emergency Medicine Consensus Conference on "The Science of Simulation in Healthcare," our breakout session critically evaluated several issues important to the use of simulation in emergency physician (EP) assessment. In this article, we discuss five topics felt to be most critical to simulation-based assessment (SBA). We then offer more specific research questions that would help to define and implement a SBA program in emergency medicine (EM). C1 [Spillane, Linda] Univ Rochester, Sch Med, Dept Emergency Med, Rochester, NY 14627 USA. [Hayden, Emily] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Fernandez, Rosemarie] Wayne State Univ, Dept Emergency Med, Detroit, MI USA. [Adler, Mark] Northwestern Univ, Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. [Adler, Mark] Northwestern Univ, Childrens Mem Hosp, Dept Emergency Med, Chicago, IL 60614 USA. [Beeson, Michael] NE Ohio Univ, Coll Med, Dept Emergency Med, Rootstown, OH 44272 USA. [Goyal, Deepi] Mayo Clin, Dept Emergency Med, Rochester, MN USA. [Smith-Coggins, Rebecca] Stanford Univ, Dept Surg Emergency Med, Stanford, CA 94305 USA. [Boulet, John] Fdn Adv Int Med Educ & Res, Philadelphia, PA USA. RP Spillane, L (reprint author), Univ Rochester, Sch Med, Dept Emergency Med, Rochester, NY 14627 USA. EM Linda_spillane@urmc.rochester.edu OI Adler, Mark/0000-0003-1857-8639 NR 58 TC 10 Z9 10 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2008 VL 15 IS 11 BP 1071 EP 1078 DI 10.1111/j.1553-2712.2008.00271.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 374NT UT WOS:000261051700014 PM 19032553 ER PT J AU Okuda, Y Bond, W Bonfante, G McLaughlin, S Spillane, L Wang, E Vozenilek, J Gordon, JA AF Okuda, Yasuharu Bond, William Bonfante, Gary McLaughlin, Steve Spillane, Linda Wang, Ernest Vozenilek, John Gordon, James A. TI National Growth in Simulation Training within Emergency Medicine Residency Programs, 2003-2008 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE simulation; postgraduate medical education; emergency medicine ID CURRICULUM AB The use of medical simulation has grown dramatically over the past decade, yet national data on the prevalence and growth of use among individual specialty training programs are lacking. The objectives of this study were to describe the current role of simulation training in emergency medicine (EM) residency programs and to quantify growth in use of the technology over the past 5 years. In follow-up of a 2006 study (2003 data), the authors distributed an updated survey to program directors (PDs) of all 179 EM residency programs operating in early 2008 (140 Accreditation Council on Graduate Medical Education [ACGME]-approved allopathic programs and 39 American Osteopathic Association [AOA]-accredited osteopathic programs). The brief survey borrowed from the prior instrument, was edited and revised, and then distributed at a national PDs meeting. Subsequent follow-up was conducted by e-mail and telephone. The survey concentrated on technology-enhanced simulation modalities beyond routine static trainers or standardized patient-actors (high-fidelity mannequin simulation, part-task/procedural simulation, and dynamic screen-based simulation). A total of 134 EM residency programs completed the updated survey, yielding an overall response rate of 75%. A total of 122 (91%) use some form of simulation in their residency training. One-hundred fourteen (85%) specifically use mannequin-simulators, compared to 33 (29%) in 2003 (p < 0.001). Mannequin-simulators are now owned by 58 (43%) of the programs, whereas only 9 (8%) had primary responsibility for such equipment in 2003 (p < 0.001). Fifty-eight (43%) of the programs reported that annual resident simulation use now averages more than 10 hours per year. Use of medical simulation has grown significantly in EM residency programs in the past 5 years and is now widespread among training programs across the country. C1 [Okuda, Yasuharu] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Okuda, Yasuharu] Mt Sinai Sch Med, Dept Med Educ, New York, NY 10029 USA. [Bond, William; Bonfante, Gary] Penn State Univ, Coll Med, Hlth Network, Bethlehem, PA USA. Lehigh Valley Hosp, Bethlehem, PA USA. [McLaughlin, Steve] Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA. [Spillane, Linda] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Wang, Ernest; Vozenilek, John] Northwestern Univ, Feinberg Sch Med, Div Emergency Med, Evanston NW Healthcare, Evanston, IL USA. [Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA USA. RP Okuda, Y (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustave L Levy Pl,Box 1149, New York, NY 10029 USA. EM yasuharu.okuda@mssm.edu OI Vozenilek, John/0000-0001-7955-4089 NR 8 TC 51 Z9 53 U1 1 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2008 VL 15 IS 11 BP 1113 EP 1116 DI 10.1111/j.1553-2712.2008.00195.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 374NT UT WOS:000261051700019 PM 18717652 ER PT J AU McLaughlin, S Fitch, MT Goyal, DG Hayden, E Kauh, CY Laack, TA Nowicki, T Okuda, Y Palm, K Pozner, CN Vozenilek, J Wang, E Gordon, JA AF McLaughlin, Steve Fitch, Michael T. Goyal, Deepi G. Hayden, Emily Kauh, Christine Yang Laack, Torrey A. Nowicki, Thomas Okuda, Yasuharu Palm, Ken Pozner, Charles N. Vozenilek, John Wang, Ernest Gordon, James A. CA SAEM Technology Med Educ Comm Simulation Interest Grp TI Simulation in graduate medical education 2008: A review for emergency medicine SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE graduate medical education; simulation ID HIGH-FIDELITY SIMULATION; AIRWAY MANAGEMENT-SKILLS; PATIENT SIMULATION; DELIBERATE PRACTICE; CLINICAL-PERFORMANCE; ANESTHESIA RESIDENTS; SHOULDER DYSTOCIA; OPERATING-ROOM; STUDENTS; CURRICULUM AB Health care simulation includes a variety of educational techniques used to complement actual patient experiences with realistic yet artificial exercises. This field is rapidly growing and is widely used in emergency medicine (EM) graduate medical education (GME) programs. We describe the state of simulation in EM resident education, including its role in learning and assessment. The use of medical simulation in GME is increasing for a number of reasons, including the limitations of the 80-hour resident work week, patient dissatisfaction with being "practiced on," a greater emphasis on patient safety, and the importance of early acquisition of complex clinical skills. Simulation-based assessment (SBA) is advancing to the point where it can revolutionize the way clinical competence is assessed in residency training programs. This article also discusses the design of simulation centers and the resources available for developing simulation programs in graduate EM education. The level of interest in these resources is evident by the numerous national EM organizations with internal working groups focusing on simulation. In the future, the health care system will likely follow the example of the airline industry, nuclear power plants, and the military, making rigorous simulation-based training and evaluation a routine part of education and practice. C1 [McLaughlin, Steve] Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA. [Fitch, Michael T.] Wake Forest Univ, Dept Emergency Med, Winston Salem, NC 27109 USA. [Goyal, Deepi G.; Laack, Torrey A.] Mayo Clin, Dept Emergency Med, Rochester, MN USA. Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA USA. [Hayden, Emily; Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kauh, Christine Yang] New York Methodist Hosp, Brooklyn, NY USA. [Nowicki, Thomas] Univ Connecticut, Farmington, CT USA. [Okuda, Yasuharu] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Palm, Ken] Vanderbilt Univ, Med Ctr, Dept Emergency Med, Nashville, TN USA. [Pozner, Charles N.] Harvard Univ, Sch Med, Brigham & Womens Hosp Emergency Med, STRATUS Ctr Med Simulat, Boston, MA USA. [Vozenilek, John] Northwestern Univ, NW McGaw Simulat Network, Feinberg Sch Med, Div Emergency Med,Evanston NW Healthcare, Evanston, IL USA. [Wang, Ernest] Northwestern Univ, Evanston Hosp, Div Emergency Med, Mcgaw Med Ctr, Evanston, IL 60201 USA. RP McLaughlin, S (reprint author), Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA. EM smclaughlin@salud.unm.edu OI Vozenilek, John/0000-0001-7955-4089 NR 96 TC 48 Z9 49 U1 6 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2008 VL 15 IS 11 BP 1117 EP 1129 DI 10.1111/j.1553-2712.2008.00188.x PG 13 WC Emergency Medicine SC Emergency Medicine GA 374NT UT WOS:000261051700020 PM 18638028 ER PT J AU Green, AR Betancourt, JR Park, ER Greer, JA Donahue, EJ Weissman, JS AF Green, Alexander R. Betancourt, Joseph R. Park, Elyse R. Greer, Joseph A. Donahue, Elizabeth J. Weissman, Joel S. TI Providing Culturally Competent Care: Residents in HRSA Title VII Funded Residency Programs Feel Better Prepared SO ACADEMIC MEDICINE LA English DT Article ID HIDDEN CURRICULUM; INTERNAL-MEDICINE; PHYSICIANS AB Background The Health Resources and Services Administration (HRSA) funds primary care residency programs through its Title VII training grants, with a goal of ensuring a well-prepared, culturally competent physician workforce. The authors sought to determine whether primary care residents in Title VII-funded training programs feel better prepared than those in nonfuncled programs to provide care to culturally diverse patients. Method The authors analyzed data from a national mailed survey of senior resident physicians conducted in 2003-2004. Of 1,467 randomly selected family medicine, internal medicine, and pediatrics residents, 866 responded-403 in Title VII-funded programs and 463 in nonfunded programs (response rate = 59%). The survey included 28 Likert-response questions about residents' preparedness and perceived skills to provide cross-cultural care, sociodemographics, and residency characteristics. Results Residents in Title VII-funded programs were more likely than others to report being prepared to provide cross-cultural care across all 8 measures (odds ratio [OR] = 1.54-2.61, P < .01) and feeling more skilled in cross-cultural care for 6 of 10 measures (OR = 1.30-1.95, P < .05). Regression analyses showed that characteristics of the Title VII-funded residency training experience related to cross-cultural care (e.g., role models, cross-cultural training, and attitudes of attending physicians) accounted for many of the differences in self-reported preparedness and skills. Conclusions Senior residents in HRSA Title VII-funded primary care residency training programs feel better prepared than others to provide culturally competent care. This may be partially explained by better cross-cultural training experiences in HRSA Title VII-funded programs. This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs. C1 [Green, Alexander R.; Betancourt, Joseph R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy,Dispar Solut Ctr, Boston, MA 02115 USA. [Green, Alexander R.] Harvard Univ, Sch Med, Cross Cultural Care Comm, Boston, MA USA. [Greer, Joseph A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. RP Green, AR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy,Dispar Solut Ctr, Boston, MA 02115 USA. EM argreen@partners.org NR 15 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 2008 VL 83 IS 11 BP 1071 EP 1079 DI 10.1097/ACM.0b013e3181890b16 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466IL UT WOS:000267654700019 PM 18971660 ER PT J AU Dubovsky, SL Gendel, MH Dubovsky, AN Levin, R Rosse, J House, R AF Dubovsky, Steven L. Gendel, Michael H. Dubovsky, Amelia N. Levin, Robert Rosse, Joseph House, Robert TI Can Admissions Interviews Predict Performance in Residency? SO ACADEMIC PSYCHIATRY LA English DT Article ID CLINICAL-PERFORMANCE; MEDICAL-SCHOOL; SELECTION; APPLICANTS; CRITERIA; PROGRAM AB Objective: The authors aim to determine whether admission interviews predict performance in residency. Methods: The authors determined whether interview and other admission data were con-elated with performance during postgraduate years 2-4 and with remaining in the residency in 544 residents enrolled in a single psychiatry residency program between 1963 and 2004. Results: Considered together; admissions data predicted 13% of the variance in performance ratings in postgraduate year 2 (PGY-2) and 5% in PGY-4. Interview scores were moderately correlated with performance ratings in PGY-2, modestly correlated with performance in PGY-3, and not cot-related with performance ratings in PGY-4. Letters of reference were moderately correlated with performance ratings in PGY-2 and modestly correlated with performance in PGY-3 and PGY-4. In PGY-2, interview scores differentiated between the top quartile of performance and the other three quartiles, while letters of reference differentiated performance in the top and bottom quartiles from the middle quartiles. Numerical differences among groups were not great enough to be practically useful, and no variables predicted which residents would leave the program before completing it. Conclusion: As they are currently conducted, application interviews do not have sufficient power to predict performance during residency. Letters of reference may be useful to the extent that they reflect personal experience with the applicant, but differences in ratings of these letters are not great enough to base admission decisions on them. As it is currently performed, the interview process may be more useful as a means of interesting applicants in the program than of evaluating their potential for success in the residency. C1 [Dubovsky, Steven L.] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14215 USA. [Gendel, Michael H.] Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. [Dubovsky, Amelia N.] Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. [Dubovsky, Amelia N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levin, Robert; Rosse, Joseph] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [House, Robert] Denver Hlth Med Ctr, Dept Psychiat, Denver, CO USA. RP Dubovsky, SL (reprint author), SUNY Buffalo, Dept Psychiat, 462 Grider St,Rm 1182, Buffalo, NY 14215 USA. EM dubovsky@buffalo.edu RI Rosse, Joseph/E-3925-2010 NR 22 TC 10 Z9 11 U1 0 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD NOV-DEC PY 2008 VL 32 IS 6 BP 498 EP 503 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 399DG UT WOS:000262780000009 PM 19190295 ER PT J AU Ghaemi, SN Wingo, AP Filkowski, MA Baldessarini, RJ AF Ghaemi, S. N. Wingo, A. P. Filkowski, M. A. Baldessarini, R. J. TI Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Review DE bipolar disorder; antidepressants; depression; mania; meta-analysis; maintenance treatment; mood stabilizers; review of the literature ID LITHIUM MAINTENANCE TREATMENT; RANDOMIZED CONTROLLED-TRIALS; CONTROLLED 18-MONTH TRIAL; DOUBLE-BLIND; I DISORDER; DEPRESSED-PATIENTS; IMIPRAMINE; CARBONATE; UNIPOLAR; COMBINATION AB Objective: Long-term antidepressant (AD) treatment for depression in bipolar disorder (BPD) patients is highly prevalent, but its benefits and risks remain uncertain, encouraging this meta-analysis of available research. Method: We reviewed randomized controlled trials for BPD involving >= 6 months of treatment with AD +/- mood stabilizer (MS) vs. placebo +/- MS, using meta-analyses to compare reported risks of new depression vs. mania. Results: In seven trials (350 BPD patients) involving 12 contrasts, long-term treatments that included ADs yielded 27% lower risk of new depression vs. MS-only or no treatment [pooled relative risk, RR = 0.73; 95% CI 0.55-0.97; number-needed-to-treat (NNT) = 11], but 72% greater risk for new mania [RR = 1.72; 95% CI 1.23-2.41; number-needed-to-harm (NNH) = 7]. Compared with giving an MS-alone, adding an AD yielded neither major protection from depression (RR = 0.84; 95% CI 0.56-1.27; NNT = 16) nor substantial increase in risk of mania (RR = 1.37; 95% CI 0.81-2.33; NNH = 16). Conclusion: Long-term adjunctive AD treatment was not superior to MS-alone in BPD, further encouraging reliance on MSs as the cornerstone of prophylaxis. C1 [Ghaemi, S. N.] Tufts Med Ctr, Mood Disorders Program, Dept Psychiat, Boston, MA USA. [Wingo, A. P.; Filkowski, M. A.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat & Neurosci Program, Boston, MA USA. [Baldessarini, R. J.] Massachusetts Gen Hosp, Psychopharmacol Program, McLean Div, Mailman Res Ctr, Belmont, MA USA. [Baldessarini, R. J.] Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, McLean Div, Mailman Res Ctr, Belmont, MA USA. RP Ghaemi, SN (reprint author), Tufts Univ, Sch Med, 800 Washington St, Boston, MA 02111 USA. EM nghaemi@tuftsmedicalcenter.org FU NIH [MH-64189]; Bruce J. Anderson Foundation; McLean Private Donors Neuropsychopharmacology Research Fund FX This study was supported in part by NIH grant MH-64189 (SNG), an award from the Bruce J. Anderson Foundation, and the McLean Private Donors Neuropsychopharmacology Research Fund (RJB). NR 49 TC 89 Z9 91 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD NOV PY 2008 VL 118 IS 5 BP 347 EP 356 DI 10.1111/j.1600-0447.2008.01257.x PG 10 WC Psychiatry SC Psychiatry GA 358RZ UT WOS:000259936500003 PM 18727689 ER PT J AU Morissette, SB Gulliver, SB Kamholz, BW Duade, J Farchione, T Devine, E Brown, TA Barlow, DH Ciraulo, D AF Morissette, Sandra B. Gulliver, Suzy B. Kamholz, Barbara W. Duade, James Farchione, Todd Devine, Eric Brown, Timothy A. Barlow, David H. Ciraulo, Domenic TI Differences between daily smokers, chippers, and nonsmokers with co-occurring anxiety and alcohol-use disorders SO ADDICTIVE BEHAVIORS LA English DT Article DE tobacco; smoking; alcohol; anxiety disorders ID PANIC DISORDER; PHOBIA QUESTIONNAIRE; NICOTINE DEPENDENCE; SMOKING; SENSITIVITY; FEAR; COMORBIDITY; PREVALENCE; VALIDATION; CIGARETTE AB Tobacco use is disproportionately represented among both alcohol-use disorders (AUDs) and anxiety disorders (ANX) compared to the general population [Kalman, D. A., Morissette, S. B., & George, T. P. (2005). Co-morbidity of nicotine and tobacco use in psychiatric and substance use disorders. The American journal on Addictions, 14,1-18]. Despite this common overlap, little is known about how smokers with co-occurring AUD-ANX differ from their nonsmoking counterparts. Seventy-two patients participated in a larger clinical trial evaluating the efficacy of venlafaxine and cognitive-behavioral therapy for AUD-ANX Differences between daily smokers (n =23), chippers (n = 12) and nonsmokers (n = 37) with AUD-ANX were examined with respect to intensity and frequency of alcohol use, anxiety symptoms, depressed mood, and stress. Point prevalence of current daily smoking was 31.9%, which is considerably lower than traditionally reported in AUD studies. Consistent with predictions, daily smokers reported higher levels of alcohol dependence, average drinks per drinking occasion, and peak blood concentration levels in a day than nonsmokers during the 90 days prior to assessment. Chippers were nonsignificantly different from either smokers or nonsmokers. Smokers and nonsmokers did not differ with respect to percent heavy drinking days or emotional symptoms. Published by Elsevier Ltd. C1 [Morissette, Sandra B.] Psychol Serv 116B, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Morissette, Sandra B.; Kamholz, Barbara W.; Devine, Eric; Barlow, David H.; Ciraulo, Domenic] Boston Univ, Sch Med, Boston, MA 02215 USA. [Morissette, Sandra B.; Kamholz, Barbara W.; Duade, James; Farchione, Todd; Brown, Timothy A.; Barlow, David H.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Gulliver, Suzy B.] Cent Texas Vet Healthcare Syst, Arlington, TX 76019 USA. RP Morissette, SB (reprint author), Psychol Serv 116B, VA Boston Healthcare Syst, 150 S Huntington St, Boston, MA 02130 USA. EM Sandra.Morissette@va.gov OI Devine, Eric/0000-0002-3713-9079; Ciraulo, Domenic/0000-0001-7706-8765 FU NIAAA [R01-AA013727]; NIDA [K23-DA16376] FX This research was supported by a NIAAA grant awarded to Dr. Ciraulo (R01-AA013727) and a NIDA grant awarded to the first author (K23-DA16376). We would like to acknowledge the assistance of several study personnel: Stella Bitran, Kendall Wilkins, Julianna Hogan, Ancy Cherian. Elizabeth LoTempio, Jenna Jawdat and Maria-Christina Stewart. NR 44 TC 12 Z9 12 U1 4 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD NOV PY 2008 VL 33 IS 11 BP 1425 EP 1431 DI 10.1016/j.addbeh.2008.06.012 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 351HD UT WOS:000259414400007 PM 18656314 ER PT J AU Hardy, DJ Castellon, SA Hinkin, CH Levine, AJ Lam, MN AF Hardy, David J. Castellon, Steven A. Hinkin, Charles H. Levine, Andrew J. Lam, Mona N. TI Sensation Seeking and Visual Selective Attention in Adults with HIV/AIDS SO AIDS AND BEHAVIOR LA English DT Article DE HIV; AIDS; Cognition; Personality; Performance; Individual differences ID INTRAVENOUS-DRUG-USERS; HIV-INFECTED ADULTS AB The association between sensation seeking and visual selective attention was examined in 31 adults with the Human Immunodeficiency Virus (HIV). Sensation seeking was measured with Zuckerman's Sensation Seeking Scale Form V (SSS-V). Selective attention was assessed with a perceptual span task, where a target letter-character must be identified in a quickly presented array of nontarget letter-characters. As predicted, sensation seeking was strongly associated (R-2 = .229) with perceptual span performance in the array size 12 condition, where selective attention demands were greatest, but not in the easier conditions. The Disinhibition, Boredom Susceptibility, and Experience Seeking subscales of the SSS-V were associated with span performance. It is argued that personality factors such as sensation seeking may play a significant role in selective attention and related cognitive abilities in HIV positive adults. Furthermore, sensation seeking differences might explain certain inconsistencies in the HIV neuropsychology literature. C1 [Hardy, David J.] Loyola Marymount Univ, Dept Psychol, Los Angeles, CA 90045 USA. [Hardy, David J.; Castellon, Steven A.; Hinkin, Charles H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Castellon, Steven A.; Hinkin, Charles H.; Lam, Mona N.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Levine, Andrew J.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Lam, Mona N.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Hardy, DJ (reprint author), Loyola Marymount Univ, Dept Psychol, Suite 4700, Los Angeles, CA 90045 USA. EM dhardy@lmu.edu FU NIA NIH HHS [R03 AG018549-01, R03 AG-18549]; NIMH NIH HHS [T32 MH019535, R01 MH-58552, T32 MH019535-18, R01 MH058552-05, R01 MH058552, T32 MH-19535] NR 12 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD NOV PY 2008 VL 12 IS 6 BP 930 EP 934 DI 10.1007/s10461-007-9288-6 PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 359CC UT WOS:000259962800012 PM 17701336 ER PT J AU Korthuis, PT Zephyrin, LC Fleishman, JA Saha, S Josephs, JS McGrath, MM Hellinger, J Gebo, KA AF Korthuis, P. Todd Zephyrin, Laurie C. Fleishman, John A. Saha, Somnath Josephs, Joshua S. McGrath, Moriah M. Hellinger, James Gebo, Kelly A. CA HIV Res Network TI Health-Related Quality of Life in HIV-Infected Patients: The Role of Substance Use SO AIDS PATIENT CARE AND STDS LA English DT Article ID MULTICENTER AIDS COHORT; UNITED-STATES; SERVICES UTILIZATION; PSYCHIATRIC-DISORDERS; ANTIRETROVIRAL THERAPY; ABUSE TREATMENT; MENTAL-HEALTH; OPIATE USERS; DRUG-USE; ADULTS AB HIV infection and substance use disorders are chronic diseases with complex contributions to health-related quality of life (HRQOL). We conducted a cross-sectional survey of 951 HIV-infected adults receiving care at 14 HIV Research Network sites in 2003 to estimate associations between HRQOL and specific substance use among HIV-infected patients. HRQOL was assessed by multi-item measures of physical and role functioning, general health, pain, energy, positive affect, anxiety, and depression. Mental and physical summary scales were developed by factor analysis. We used linear regression to estimate adjusted associations between HRQOL and current illicit use of marijuana, analgesics, heroin, amphetamines, cocaine, sedatives, inhalants, hazardous/binge alcohol, and drug use severity. Current illicit drug use was reported by 37% of subjects. Mental HRQOL was reduced for current users [adjusted beta coefficient -9.66, 95% confidence interval [(CI]) -13.4, -5.94] but not former users compared with never users. Amphetamines and sedatives were associated with large decreases in mental (amphetamines: beta = -22.8 [95% CI -33.5, -12.0], sedatives: beta = -18.6 [95% CI -26.2, -11.0]), and physical HRQOL (amphetamines: beta = -11.5 [95% CI -22.6, -0.43], sedatives: beta = -13.2 [95% CI -21.0, -5.36]). All illicit drugs were associated with decreased mental HRQOL: marijuana (beta = -7.72 [95% CI -12.0, -3.48]), non-prescription analgesics (beta = -13.4 [95% CI -20.8, -6.07]), cocaine (beta = -10.5 [95% CI -16.4, -4.67]), and inhalants (beta = -14.0 [95% CI -24.1, -3.83]). Facilitating sobriety for patients with attention to specific illicit drugs represents an important avenue for elevating HRQOL in patients living with HIV. C1 [Korthuis, P. Todd; Saha, Somnath; McGrath, Moriah M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Zephyrin, Laurie C.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Fleishman, John A.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Josephs, Joshua S.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Hellinger, James] Community Med Alliance, Boston, MA USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu FU Agency for Healthcare Research and Quality [290-01-0012]; National Institutes of Aging [R01 AG026250, K23 AA015313, K23-DA00523, K-23-DA019820]; Department of Veterans Affairs Health Services Research & Development Service; Robert Wood Johnson Foundation; Johns Hopkins Clinician Scientist FX Participating Sites: Alameda County Medical Center, Oakland, California (Silver Sisneros, D. O.); Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (Richard Rutstein, M. D.); Community Health Network, Rochester, New York (Roberto Corales, D. O.); Community Medical Alliance, Boston, Massachusetts (James Hellinger, M. D.); Drexel University, Philadelphia, Pennsylvania (Peter Sklar, M. D.); Henry Ford Hospital Detroit, Michigan (Norman Markowitz, M. D.); Johns Hopkins University, Baltimore, Maryland (Kelly Gebo, M. D., Richard Moore, M. D); Montefiore Medical Group, Bronx, New York (Robert Beil, M. D.); Montefiore Medical Center, Bronx, New York (Lawrence Hanau, M. D.); Nemechek Health Renewal, Kansas City, Missouri (Patrick Nemechek, D. O.); Oregon Health and Science University, Portland, Oregon (P. Todd Korthuis, M. D.); Parkland Health and Hospital System, Dallas, Texas (Philip Keiser, M. D.); St. Jude's Children's Hospital and University of Tennessee, Memphis, Tennessee (Aditya Gaur, M. D.); St. Luke's Roosevelt Hospital Center, New York, New York (Victoria Sharp, M. D.); Tampa General Health Care, Tampa, Florida (Charurut Somboonwit, M. D., Jeffrey Nadler, M. D.); University of California, San Diego, La Jolla, California (Stephen Spector, M. D.); University of California, San Diego, California (W. Christopher Mathews, M. D.); Wayne State University, Detroit, Michigan (Lawrence Crane, M. D.).; Sponsoring Agencies: Agency for Healthcare Research and Quality, Rockville, Maryland (Fred Hellinger, Ph. D., John Fleishman, Ph. D., Irene Fraser, Ph. D.); Health Resources and Services Administration, Rockville, Maryland (Alice Kroliczak, Ph. D., Robert Mills, Ph. D., Richard Conviser, Ph. D.); Substance Abuse and Mental Health Services Administration, Rockville, Maryland (Laura House, Ph. D., Joan Dilonardo, Ph. D.); Office of AIDS Research, NIH, Bethesda, Maryland (Paul Gaist, Ph. D, M. P. H.).; Supported by the Agency for Healthcare Research and Quality (290-01-0012) and the National Institutes of Aging (R01 AG026250) Alcohol (K23 AA015313) and Drug Abuse (K23-DA00523 and K-23-DA019820). Dr. Saha is supported by an Advanced Research Career Development Award from the Department of Veterans Affairs Health Services Research & Development Service, and a Generalist Physician Faculty Scholar Award from The Robert Wood Johnson Foundation. Dr. Gebo also received support from a Johns Hopkins Clinician Scientist Award.; The views expressed in this paper are those of the authors. No official endorsement by DHHS, the National Institutes of Health, the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, or the Department of Veterans Affairs is intended or should be inferred. NR 48 TC 35 Z9 36 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 2008 VL 22 IS 11 BP 859 EP 867 DI 10.1089/apc.2008.0005 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 378SM UT WOS:000261344200004 PM 19025480 ER PT J AU Durazzo, TC Gazdzinski, S Yeh, PH Meyerhoff, DJ AF Durazzo, Timothy C. Gazdzinski, Stefan Yeh, Ping-Hong Meyerhoff, Dieter J. TI Combined Neuroimaging, Neurocognitive and Psychiatric Factors to Predict Alcohol Consumption Following Treatment for Alcohol Dependence SO ALCOHOL AND ALCOHOLISM LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; MAJOR DEPRESSIVE DISORDER; POSTTREATMENT ALCOHOLICS; CLINICAL-IMPLICATIONS; COGNITIVE EFFICIENCY; ABSTINENT ALCOHOLICS; N-ACETYLASPARTATE; FEMALE ALCOHOLICS; PREFRONTAL CORTEX; BIPOLAR DISORDER AB Aims: Resumption of hazardous drinking after treatment is common in alcohol use disorders (AUD). This study examined the ability of multimodality magnetic resonance, neurocognitive, psychiatric and demographic, to predict alcohol consumption after treatment for AUD. Methods: Seventy treatment-seeking participants completed 1.5T magnetic resonance studies, yielding regional gray matter (GM) and white matter (WM) surrogate markers of neuronal integrity (N-acetylaspartate: NAA) and cell membrane turnover/synthesis (choline: Cho), assessment of major psychiatric disorders and comprehensive neurocognitive assessment after similar to 1 month of abstinence. Participants were followed up 6-12 months after treatment and classified as Abstainers (no alcohol consumption; n = 26) and Resumers (any alcohol consumption; n = 44). Abstainers and Resumers were contrasted on various outcome measures, and those that significantly differed between groups were entered as factors in a logistical regression model to predict drinking status at follow-up. Results: The following variables were independent predictors of resumption of drinking: temporal GM NAA, frontal WM NAA, frontal GM Cho, processing speed and comorbid unipolar mood disorder. With each standard deviation unit decrease in temporal GM NAA, frontal WM NAA, frontal GM Cho and processing speed, the odds of resumption of drinking were increased 3.1, 3.3, 6.4 and 14.2 times, respectively. Diagnosis of a unipolar mood disorder was associated with 14.5-fold increased odds of resumed drinking. Conclusions: The findings suggest that Resumers, relative to Abstainers, demonstrated greater abnormalities in anterior frontal-subcortical circuits involved in mood and behavioral regulation, and development and maintenance of alcohol use disorders, The magnetic resonance-derived variables used in this study may provide additional information regarding the prediction and neurobiological correlates of resumption of hazardous drinking. C1 [Durazzo, Timothy C.; Yeh, Ping-Hong; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Durazzo, Timothy C.; Gazdzinski, Stefan; Yeh, Ping-Hong; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU NIH [AA10788] FX This project was supported by NIH AA10788 (D. J. M.). We thank Mary RebeccaYoung and Bill Clift of the VA Substance Abuse Day Hospital and Dr David Pating, Karen Moise and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 95 TC 39 Z9 39 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD NOV-DEC PY 2008 VL 43 IS 6 BP 683 EP 691 DI 10.1093/alcalc/agn078 PG 9 WC Substance Abuse SC Substance Abuse GA 365BN UT WOS:000260381000015 PM 18818189 ER PT J AU Voronin, K Randall, P Myrick, H Anton, R AF Voronin, Konstantin Randall, Patrick Myrick, Hugh Anton, Raymond TI Aripiprazole Effects on Alcohol Consumption and Subjective Reports in a Clinical Laboratory Paradigm-Possible Influence of Self-Control SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Aripiprazole; Laboratory; Treatment ID CUE-INDUCED ACTIVATION; EXTRACELLULAR DOPAMINE; ABSTINENT ALCOHOLICS; ETHANOL-CONSUMPTION; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; IMAGING EVIDENCE; SOCIAL DRINKERS; DRUG-ADDICTION; C57BL/6 MICE AB Introduction: There has been increasing interest in the use of medications that affect the dopamine receptor in the treatment of alcoholism. Aripiprazole has the unique pharmacology of being a partial dopamine agonist serving to stabilize brain dopamine systems in both frontal cortical and subcortical areas. As such, it might act to dampen alcohol reinforcement and craving and/or alter control over alcohol use. The current clinical laboratory study was conducted to evaluate the safety and efficacy of aripiprazole as a potential agent to alter drinking and objective effects of alcohol. Methods: Thirty nontreatment seeking alcoholics were enrolled in a subacute human laboratory study and received double-blind treatment with up to 15 mg of aripiprazole (n = 15) or identical placebo (n = 15) for 8 days. Tolerability and utility of aripiprazole was monitored during natural drinking over the first 6 days of medication treatment and also during a free choice limited access alcohol consumption paradigm following an initial drink of alcohol in a bar-lab setting on Day 8. Results: Aripiprazole was well tolerated and reduced drinking in nontreatment seeking alcoholics over 6 days of natural drinking-especially in those with lower self control (more impulsive). It also reduced drinks in the bar-lab after a priming drink and broke the link between priming drink induced stimulation and further drinking. During the bar-lab drinking session, there were no differences in subjective high, intoxication, or craving between subjects treated with aripiprazole or placebo. Discussion: This study joins several others in demonstrating the utility of subacute dosing laboratory paradigms for evaluating medication effects in alcoholics. Aripiprazole was well tolerated and lowered alcohol use, especially in those with lower impulse control. Further study is needed to determine the safety and utility of aripiprazole in the treatment of alcoholism and if subgroups of alcoholics are more likely to respond. C1 [Voronin, Konstantin; Randall, Patrick; Myrick, Hugh; Anton, Raymond] Med Univ S Carolina, Dept Psychiat & Behav Sci, Alcohol Res Ctr, Charleston, SC 29425 USA. [Myrick, Hugh] Res & Dev Serv, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Voronin, K (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Alcohol Res Ctr, IOP 4N,67 President St, Charleston, SC 29425 USA. EM voronin@musc.edu FU Alcohol Research Center [P50 AA010761] FX Abraham Tiffany assisted in collection of data. Nancy White and Mary Evelyn Boyd assisted in preparation of this manuscript. Supported was granted by Alcohol Research Center Grant P50 AA010761. NR 57 TC 31 Z9 32 U1 5 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2008 VL 32 IS 11 BP 1954 EP 1961 DI 10.1111/j.1530-0277.2008.00783.x PG 8 WC Substance Abuse SC Substance Abuse GA 362FK UT WOS:000260183400012 PM 18782344 ER PT J AU Hachem, CY Kramer, JR Kanwal, F El-Serag, HB AF Hachem, C. Y. Kramer, J. R. Kanwal, F. El-Serag, H. B. TI Hepatitis vaccination in patients with hepatitis C: practice and validation of codes at a large veterans administration medical centre SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CHRONIC LIVER-DISEASE; VIRUS SUPERINFECTION; B VACCINATION; QUALITY; CARE; IMMUNOGENICITY; INFECTION; AGREEMENT; CIRRHOSIS AB Background Hepatitis vaccination is recommended in patients with chronic liver disease. Aim To validate Current Procedural Terminology (CPT) codes and drug codes for hepatitis vaccination in administrative databases and determine vaccination rates in hepatitis C virus (HCV)-infected patients in a single large Veterans Administration Medical Center. Methods We calculated predictive values for hepatitis vaccination codes in a validation set of 168 patients. We then conducted a retrospective cohort study of 243 HCV-infected patients to determine rates of hepatitis vaccination and serological testing. Results The presence of CPT or drug codes for hepatitis A vaccine yielded a positive predictive value (PPV) and negative predictive value (NPV) of 93.2% and 94.0%. The presence of hepatitis B vaccine codes yielded a PPV of 98.0% and an NPV of 94.0%. Among patients diagnosed with HCV between 2000 and 2005, receipt of hepatitis vaccination was documented in approximately 8% overall and 7% in patients with cirrhosis. Half of the patients without hepatitis vaccinations were either not tested for immunity or had negative serology. Conclusions Current Procedural Terminology or drug codes for hepatitis vaccinations in administrative data are highly predictive of the presence of vaccinations in medical records. Our data suggest that there is significant under-utilization of vaccination in patients with HCV. C1 [Hachem, C. Y.; Kramer, J. R.; El-Serag, H. B.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Hachem, C. Y.; Kramer, J. R.; El-Serag, H. B.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Hachem, C. Y.; El-Serag, H. B.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. [Hachem, C. Y.; Kanwal, F.] St Louis Univ, Dept Med, St Louis, MO 63103 USA. RP Hachem, CY (reprint author), 3635 Vista Ave, St Louis, MO 63130 USA. EM chachem@slu.edu FU Health Services Research and Development Service; Office of Research and Development; Department of Veterans Affairs [MRP05-315, RCD00-013-2]; NIH [NCI R01 125487] FX Declaration of personal interests: None. Declaration of funding interests: This material is based on work supported in part by Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs, grant MRP05-315 to Dr Kramer and grant RCD00-013-2 to Dr El-Serag as well as funding (NIH NCI R01 125487) to Dr El-Serag and a grant to Dr Hachem from Bristol-Meyers Squibb as a part of the Virology Fellows Research Training Programme. NR 30 TC 15 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD NOV 1 PY 2008 VL 28 IS 9 BP 1078 EP 1087 DI 10.1111/j.1365-2036.2008.03827.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 357QX UT WOS:000259862300004 PM 18691350 ER PT J AU Kanwal, F Spiegel, BMR Hays, RD Durazo, F Han, SB Saab, S Bolus, R Kim, SJ Gralnek, IM AF Kanwal, F. Spiegel, B. M. R. Hays, R. D. Durazo, F. Han, S. B. Saab, S. Bolus, R. Kim, S. J. Gralnek, I. M. TI Prospective validation of the short form liver disease quality of life instrument SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID UNITED-STATES; TRANSPLANTATION; IMPACT; RELIABILITY; MEANINGFUL; CARCINOMA; CIRRHOSIS; SEVERITY; VALIDITY; INDEXES AB Background Despite the realization that health-related quality of life (HRQOL) is an important outcome in patients with liver disease, there is scarcity of disease-targeted HRQOL measures that have undergone prospective evaluation. Aim To validate prospectively the short form of liver disease quality of life instrument (the SF-LDQOL) in patients with advanced liver disease. Methods The SF-LDQOL includes 36 disease-targeted items representing nine domains: symptoms of liver disease, effects of liver disease, memory/concentration, sleep, hopelessness, distress, loneliness, stigma of liver disease and sexual problems. We administered the SF-LDQOL to 156 advanced liver disease patients at baseline and at 6-month follow-up. We estimated internal consistency reliability for multi-item scales, item discrimination across scale and evaluated construct validity by estimating the associations of SF-LDQOL scores with SF-36 scores, symptom severity and disability days. To evaluate the SF-LDQOL's responsiveness, we compared HRQOL changes for patients who received with those who did not receive liver transplantation (LT). Results The internal consistency reliability coefficients were >= 0.70 for seven of nine scales in baseline and for all scales in follow-up administration. The SF-LDQOL correlated highly with SF-36 scores, symptom severity, disability days and global health. Patients undergoing LT reported improved HRQOL compared with patients without LT and the responsiveness indices were excellent. Conclusions This study provides support for the reliability and validity of the SF-LDQOL in patients with advanced chronic liver disease. This instrument may be useful in everyday clinical practice and in future clinical trials. C1 [Gralnek, I. M.] Technion Israel Inst Technol, Rappaport Fac Med, Dept Gastroenterol, Rambam Med Ctr, IL-31096 Haifa, Israel. [Hays, R. D.] RAND Corp, Santa Monica, CA USA. [Kanwal, F.] St Louis Univ, Div Gastroenterol, St Louis, MO 63103 USA. [Kanwal, F.] John Cochran VA Med Ctr, St Louis, MO USA. [Kanwal, F.; Spiegel, B. M. R.; Bolus, R.; Kim, S. J.] Univ Calif Los Angeles, Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Spiegel, B. M. R.; Hays, R. D.; Durazo, F.; Han, S. B.; Saab, S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Los Angeles, CA 90095 USA. [Han, S. B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Gralnek, IM (reprint author), Technion Israel Inst Technol, Rappaport Fac Med, Dept Gastroenterol, Rambam Med Ctr, Rambam Hlth Care Campus, IL-31096 Haifa, Israel. EM i_gralnek@rambam.health.gov.il RI Hays, Ronald/D-5629-2013 FU American College of Gastroenterology Clinical Research Award 2003-2004 FX Declaration of funding interests: This study was funded by the American College of Gastroenterology Clinical Research Award 2003-2004. NR 43 TC 14 Z9 14 U1 13 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD NOV 1 PY 2008 VL 28 IS 9 BP 1088 EP 1101 DI 10.1111/j.1365-2036.2008.03817.x PG 14 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 357QX UT WOS:000259862300005 PM 18671776 ER PT J AU Herbert, MR AF Herbert, Martha R. TI LEARNING FROM THE AUTISM CATASTROPHE: KEY LEVERAGE POINTS SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Editorial Material C1 [Herbert, Martha R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Herbert, Martha R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Herbert, MR (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD NOV-DEC PY 2008 VL 14 IS 6 SI SI BP 28 EP 30 PG 3 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA V12YU UT WOS:000207635300007 PM 19043935 ER PT J AU Co, JPT Mohamed, H Kelleher, ML Edgman-Levitan, S Perrin, JM AF Co, John Patrick T. Mohamed, Hodon Kelleher, Mary Louise Edgman-Levitan, Susan Perrin, James M. TI Feasibility of Using a Tablet Computer Survey for Parental Assessment of Resident Communication Skills SO AMBULATORY PEDIATRICS LA English DT Article DE assessment; communication; information technology; resident; survey ID CARE AB Background.-The Accreditation Council for Graduate Medical Education recommends using patient surveys for assessing resident competency in interpersonal and communication skills. Despite the existence of several validated patient surveys for communication assessment, no system has been developed for their sustained use in resident assessment. Methods.-We developed and pilot tested a system to collect surveys from parents of hospitalized children on the day of discharge. We used a 28-item, tablet computer-based survey that measures individual provider and team communication. The computer displays resident photographs to ensure accurate identification and offers the survey in multiple languages. We assessed parental acceptance of the system by analyzing response rate, as well as reasons for response and nonresponse. Results.-Of the 98 eligible parents that were approached, 62 (63%) completed the survey. Only 2 (2%) of the eligible families refused to participate, and only 5 (5%) refused participation because of the survey not being available in a language they were familiar with. Conclusions.-Use of a tablet computer parent survey for resident assessment is feasible, with response rates comparable to those of mailed surveys. The low rate of parental refusal indicates our system could be used to attain sufficient numbers of survey responses to help validly measure resident communication skills. C1 [Co, John Patrick T.; Perrin, James M.] MGH Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Mohamed, Hodon; Kelleher, Mary Louise] MassGen Hosp Children, Boston, MA USA. [Edgman-Levitan, Susan] John Stoeckle Ctr Primary Care Innovat, Boston, MA USA. RP Co, JPT (reprint author), 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jco@partners.org FU Curtis Prout Academy; Massachusetts General Hospital; John Patrick T. Co FX This project was funded by the Curtis Prout Academy Fellowship at Harvard Medical School, the Massachusetts General Hospital Making a Difference Grant Program, and an Association of Pediatric Program Director's Special Project Grant (John Patrick T. Co). NR 10 TC 4 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD NOV-DEC PY 2008 VL 8 IS 6 BP 375 EP 378 PG 4 WC Pediatrics SC Pediatrics GA 377MS UT WOS:000261255900008 PM 19084787 ER PT J AU Cannon, CP Giugliano, RP Blazing, MA Harrington, RA Peterson, JL Sisk, CM Strony, J Musliner, TA McCabe, CH Veltri, E Braunwald, E Califf, RM AF Cannon, Christopher P. Giugliano, Robert P. Blazing, Michael A. Harrington, Robert A. Peterson, John L. Sisk, Christine McCrary Strony, John Musliner, Thomas A. McCabe, Carolyn H. Veltri, Enrico Braunwald, Eugene Califf, Robert M. CA IMPROVE-IT Inves TI Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): Comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; PLACEBO-CONTROLLED TRIAL; LOW-DENSITY-LIPOPROTEIN; STATIN THERAPY; FAMILIAL HYPERCHOLESTEROLEMIA; CHOLESTEROL ABSORPTION; RANDOMIZED-TRIAL; ARTERY-DISEASE; HEART-DISEASE; EZETIMIBE AB Background Reduction in low-density lipoprotein cholesterol (LDL-C) improves clinical outcomes in patients with chronic coronary artery disease and acute coronary syndromes (ACSs). The combination of ezetimibe/simvastatin produces greater reductions in LDL-C compared to simvastatin monotherapy. The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is a multicenter, randomized, double-blind, active-control trial designed to test the hypothesis that the addition of ezetimibe to statin therapy, using ezetimibe/simvastatin, will translate into increased clinical benefit on cardiovascular outcomes relative to simvastatin monotherapy in patients with ACS. Study Design The study will recruit up to 18,000 moderate- to high-risk patients stabilized after ACS. Patients are randomized in a 1:1 ratio to once-daily doses of either ezetimibe/simvastatin 10/40 mg or simvastatin monotherapy 40 mg. Follow-up visits are at I and 4 months, and every 4 months thereafter. If consecutive measures of LDL-C are >79 mg/dL at follow-up visits, the simvastatin dose will be increased to 80 mg in a double-blind manner. The primary end point is the first occurrence of cardiovascular death, nonfatal myocardial infarction, rehospitalization for unstable angina, coronary revascularization (occurring at least 30 days after randomization), or stroke. Patients will be followed for a minimum of 2.5 years and until at least 5,250 patients experience a primary end point. Summary IMPROVE-IT will determine whether the addition of ezetimibe to statin therapy, using ezetimibe/simvastatin, improves cardiovascular outcomes compared with simvastatin monotherapy in patients after ACS. In addition, the difference in achieved LDL-C levels between the groups will provide data on whether the target for LDL-C lowering should be reduced further. (Am Heart J 2008; 156:826-32.) C1 [Cannon, Christopher P.; Giugliano, Robert P.; McCabe, Carolyn H.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Blazing, Michael A.; Harrington, Robert A.; Peterson, John L.; Califf, Robert M.] Duke Clin Res Inst, Durham, NC USA. [Strony, John; McCabe, Carolyn H.] Merck & Co Inc, Rahway, NJ 07065 USA. [Peterson, John L.] Schering Plough Corp, Kenilworth, NJ USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org OI Van de Werf, Frans/0000-0001-9479-7767 NR 32 TC 175 Z9 183 U1 3 U2 22 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2008 VL 156 IS 5 BP 826 EP 832 DI 10.1016/j.ahj.2008.07.023 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 369NB UT WOS:000260700100007 PM 19061694 ER PT J AU Goto, S Hatt, DL Rother, J Alberts, M Hill, MD Ikeda, Y Uchiyama, S D'Agostino, R Ohman, EM Liau, CS Hirsch, AT Mas, JL Wilson, PWF Corbalan, R Aichner, F Steg, PG AF Goto, Shinya Hatt, Deepak L. Roether, Joachim Alberts, Mark Hill, Michael D. Ikeda, Yasuo Uchiyama, Shinichiro D'Agostino, Ralph Ohman, E. Magnus Liau, Chiau-Suong Hirsch, Alan T. Mas, Jean-Louis Wilson, Peter W. F. Corbalan, Ramon Aichner, Franz Steg, P. Gabriel CA REACH Registry Invest TI Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis SO AMERICAN HEART JOURNAL LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; RISK-FACTORS; STROKE PREVENTION; ANTITHROMBOTIC THERAPY; CLASSIFICATION SCHEMES; ANTIPLATELET THERAPY; PREDICTING STROKE; LIFETIME RISK; ASPIRIN AB Background Atrial fibrillation (AF) is a major risk factor (RF) for ischemic stroke. Its prevalence and prognostic impact in patients with atherothrombosis are unclear. Methods Risk factors, drug usage, and 1-year cardiovascular (CV) outcomes (CV death, myocardial infarction [MI], and stroke) were compared in AF and non-AF patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of 68,236 stable outpatients with established otherothrombosis or >= 3 atherothrombotic RFs. Result Atrial fibrillation and 1-year follow-up data are available for 63,589 patients. The prevalence of AF was, 12.5%, 13.7%, 11.5%, and 6.2% among coronary artery disease, CV disease, peripheral artery disease, and RF-only patients, respectively. Of the 6,814 patients with AF, 6.7% experienced CV death, nonfatal MI, or nonfatal stroke within a year. The annual incidence of nonfatal stroke (2.4% vs 1.6%, P < .0001) and unstable angina (6.0% vs 4.0%, P < .00001) was higher, and CV death was more than double (3.2% vs 1.4%, P < .0001), in AF versus non-AF patients. In these patients with or at high risk of atherothrombosis, most patients with AF received antiplatelet agents, but only 53.1% were treated with oral anticoagulants. Even with high CHADS(2) (congestive heart failure, hypertension, aging, diabetes mellitus, and stroke) scores, anticoagulant use did not exceed (59%). The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients (1.5% vs 0.8%, P < .0001), possibly related to the more frequent use of anticoagulants (53.1% vs 7.1%). Conclusions Atrial fibrillation is common in patients with atherothrombosis, associated with more frequent fatal and nonfatal CV outcomes, and underuse of oral anticoagulants. (Am Heart J 2008; 156:855-63.) C1 [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Isehara, Kanagawa 2591143, Japan. [Goto, Shinya] Tokai Univ, Sch Med, Metab Dis Ctr, Dept Metab Syst Med,Res Inst Med, Isehara, Kanagawa 2591143, Japan. [Roether, Joachim] VA Boston Healthcare Syst, Boston, MA USA. [Roether, Joachim] Brigham & Womens Hosp, Boston, MA 02115 USA. [Roether, Joachim] Klinikum Minden, Dept Neurol, Minden, Germany. [Alberts, Mark] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Hill, Michael D.] Foothills Med Ctr, Dept Clin Neurosci, Calgary, AB, Canada. [Ikeda, Yasuo] Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan. [Uchiyama, Shinichiro] Tokyo Womens Med Coll, Dept Neurol, Tokyo 162, Japan. [D'Agostino, Ralph] Boston Univ, Stat & Consulting Unit, Boston, MA 02215 USA. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. [Liau, Chiau-Suong] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Liau, Chiau-Suong] Sch Med, Taipei, Taiwan. [Hirsch, Alan T.] Univ Minnesota, Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Mas, Jean-Louis] Hop St Anne, Ctr Raymond Garcin, Serv Neurol, F-75674 Paris, France. [Wilson, Peter W. F.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Corbalan, Ramon] Acad Teaching Hosp Wagner Jauregg, Linz, Austria. [Aichner, Franz] Pontificia Univ Catolica Chile, Fac Med, Santiago, Chile. [Steg, P. Gabriel] INSERM, U698, Paris, France. [Steg, P. Gabriel] Univ Paris 07, Hop Bichat Claude Bernard, Paris, France. RP Goto, S (reprint author), Tokai Univ, Sch Med, Dept Med, Isehara, Kanagawa 2591143, Japan. EM shinichi@is.icc.u-tokai.ac.ip RI 段, 沛沛/C-9902-2010; Hill, Michael/C-9073-2012; OI Hill, Michael/0000-0002-6269-1543; ELISAF, MOSES/0000-0003-0505-078X NR 37 TC 123 Z9 133 U1 6 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD NOV PY 2008 VL 156 IS 5 BP 855 EP 863 DI 10.1016/j.ahj.2008.06.029 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 369NB UT WOS:000260700100011 PM 19061698 ER PT J AU Hoffmann, U Massaro, JM Fox, CS Manders, E O'Donnell, CJ AF Hoffmann, Udo Massaro, Joseph M. Fox, Caroline S. Manders, Emily O'Donnell, Christopher J. TI Defining Normal Distributions of Coronary Artery Calcium in Women and Men (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; RISK-ASSESSMENT; CT; REPRODUCIBILITY; QUANTIFICATION; GENDER; COHORT; MESA; AGE AB Coronary artery calcium (CAC) may improve risk stratification for patients with coronary heart disease (CRD) beyond traditional risk factors. Subjects from the Framingham Heart Study Offspring and Third Generation cohorts (48% women; mean age 53 years) underwent noncontrast electrocardiographically triggered cardiac multidetector computed tomography. The prevalence of absolute CAC (Agatston score [AS] >0, >100, and >400) and relative age- and gender-specific strata (25th, 50th, 75th, 90th, and 95th percentiles) were determined in a healthy subset free of clinically apparent cardiovascular disease or CHD risk factors (n = 1,586), the overall sample at risk (n = 3,238), and subjects at intermediate Framingham risk score (FRS; 6% to 20% 10-year CHD event risk; n = 1,177). Absolute AS and relative cutoffs for CAC increased with age and FRS, were higher in men compared with women in each of the 3 cohorts, and increased from the healthy subset to the overall cohort to subjects at intermediate risk. However, in subjects with CAC, there was substantial disagreement between absolute and relative cut-off values for labeling subjects as having increased CAC. In general, more subjects were considered to have increased CAC using relative cut-off values, especially in women and younger subjects. Fewer subjects at intermediate FRS had increased CAC using comparable absolute versus relative cutoffs (men 32% at AS > 100 vs 36% at > 75th percentile; women 24% at AS > 100 vs 34% at >75th percentile). In conclusion, we provided distributions of CAC in a healthy subset, the overall cohort, and subjects at intermediate risk from the Framingham Heart Study for both absolute and relative cut-off values for CAC. Absolute cutoffs underestimated the proportion of subjects with increased CAC, specifically in women, younger persons, and persons at intermediate CHD risk. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Cardiac MR PET CT Program, Boston, MA 02115 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fox, Caroline S.; Manders, Emily; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiol Div, Boston, MA USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Cardiac MR PET CT Program, Boston, MA 02115 USA. EM uhoffmann@partners.org OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart. Lung, and Blood Institute (NHLBI) Framingham Heart Study [N01-HC-25195] FX This work was supported by the National Heart. Lung, and Blood Institute (NHLBI) Framingham Heart Study (National Institutes Of Health/NHLBI Contract N01-HC-25195. Bethesda. maryland), Framingham, Massachusetts. NR 13 TC 58 Z9 63 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2008 VL 102 IS 9 BP 1136 EP 1141 DI 10.1016/j.amjcard.2008.06.038 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373XT UT WOS:000261007500004 PM 18940279 ER PT J AU McElrath, TF Hecht, JL Dammann, O Boggess, K Onderdonk, A Markenson, G Harper, M Delpapa, E Allred, EN Leviton, A AF McElrath, T. F. Hecht, J. L. Dammann, O. Boggess, K. Onderdonk, A. Markenson, G. Harper, M. Delpapa, E. Allred, E. N. Leviton, A. TI McElrath et al. Respond to "Disaggregating Preterm Birth" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 [McElrath, T. F.] Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA. [Hecht, J. L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Dammann, O.] Tufts Floating Hosp Children, Div Newborn Med, Boston, MA USA. [Boggess, K.] Univ N Carolina, Chapel Hill, NC USA. [Onderdonk, A.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Markenson, G.] Bay State Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. [Harper, M.] Wake Forest Univ, Baptist Med Ctr, Dept Maternal Fetal Med, Winston Salem, NC 27109 USA. [Delpapa, E.] Univ Massachusetts, Mem Med Ctr, Dept Obstet & Gynecol, Worcester, MA 01605 USA. [Allred, E. N.; Leviton, A.] Childrens Hosp, Neuroepidemiol Unit, Boston, MA 02115 USA. RP McElrath, TF (reprint author), Brigham & Womens Hosp, Div Maternal Fetal Med, 75 Francis St, Boston, MA 02115 USA. EM tmcelrath@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2008 VL 168 IS 9 BP 993 EP 994 DI 10.1093/aje/kwn196 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 365BM UT WOS:000260380900004 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Medical Groundhog Days SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material C1 Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2008 VL 103 IS 11 BP 2681 EP 2682 DI 10.1111/j.1572-0241.2008.02143.x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367HU UT WOS:000260543900002 PM 19032463 ER PT J AU Byfield, SAD Syngal, S AF Byfield, Stacey A. DaCosta Syngal, Sapna TI Clinical Guidelines Versus Universal Molecular Testing: Are We Ready to Choose an Optimal Strategy for Lynch Syndrome Identification? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID NONPOLYPOSIS COLORECTAL-CANCER; REVISED BETHESDA GUIDELINES; MICROSATELLITE INSTABILITY; MUTATIONS; SURVEILLANCE; PREDICTION; CARRIERS; HISTORY; HNPCC AB Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of inherited colorectal cancer (CRC). Affected individuals need to undergo intensive CRC surveillance, screening for associated cancers, and possibly prophylactic surgery. Clinically-based guidelines have been used as the basis for Lynch syndrome screening in CRC patient populations. More recently, it has been argued that the universal molecular testing strategies should be implemented to increase the identification of patients who should get germline testing for Lynch syndrome. In this issue of American Journal of Gastroenterology, Julie et al. compare the performance of clinical guidelines with a molecular strategy based on universal microsatellite instability (MSI) testing for identifying CRC patients who have Lynch syndrome. Although there is insufficient evidence to support universal molecular testing for all CRC patients at the current time, the study highlights the need for a systematic approach to identify patients with Lynch syndrome. Physicians and health care systems need to do a better job of identifying patients and families with early-onset of CRC and/or a consistent cancer family history so that they may undergo appropriate molecular evaluation, genetic counseling, and cancer risk management. C1 [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Byfield, Stacey A. DaCosta] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA92203-04, K24 CA113433, R25 CA092203] NR 20 TC 9 Z9 9 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2008 VL 103 IS 11 BP 2837 EP 2840 DI 10.1111/j.1572-0241.2008.02091.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367HU UT WOS:000260543900021 PM 19032469 ER PT J AU Chan, FKL Abraham, NS Scheiman, JM Laine, L AF Chan, Francis K. L. Abraham, Neena S. Scheiman, James M. Laine, Loren CA First Int Working Party Gastrointe TI Management of Patients on Nonsteroidal Anti-inflammatory Drugs: A Clinical Practice Recommendation From the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID LOW-DOSE ASPIRIN; SELECTIVE CYCLO-OXYGENASE-2 INHIBITORS; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; HIGH-RISK; COX-2 INHIBITORS; PREVENTION; TRIAL; COMPLICATIONS; GUIDELINES AB BACKGROUND: Prescribing nonsteroidal antiinflammatory drugs (NSAIDs) is challenging because physicians have to consider gastrointestinal (GI) and cardiovascular (CV) safety issues. OBJECTIVE: The purpose of the study was to determine appropriate NSAID treatment strategies based on different combinations of GI and CV risks. METHODS: The working party comprised a multidisciplinary international panel of 19 experts. Two hundred eighty-eight vignettes were evaluated for the appropriateness of each of six options: naproxen, non-naproxen nonselective NSAIDs, naproxen plus proton pump inhibitor (PPI)/misoprostol, non-naproxen nonselective NSAID plus PPI/misoprostol, cyclooxygenase-2 selective NSAID (coxib), or coxib plus PPI/misoprostol. Using a two-stage modified Delphi process, the panel anonymously ranked the appropriateness of each option from 1 (extremely inappropriate) to 9 (extremely appropriate). Vignettes were considered appropriate if >= 80% of all panelists' scores were 7-9 and inappropriate if >= 80% of all panelists' scores were 1-3. RESULTS: The panel rated nonselective NSAIDs as appropriate when the patient had average GI risk (< 70 yr of age; no prior upper GI event; no corticosteroids, antithrombotic agents, anticoagulants). In patients with GI risk factors, cotherapy with a PPI/misoprostol was appropriate. Either a nonselective NSAID or a coxib was rated appropriate in patients with average CV risk; naproxen was preferred in patients with high CV risk. None of the options was considered appropriate in patients with multiple GI risk factors and high CV risk. CONCLUSIONS: The initial choice of an NSAID (naproxen vs. others) relates to a patient's CV risk, and the need for therapy to decrease GI complications (PPI/misoprostol or coxibs) is determined by severity and number of GI risk factors. C1 [Chan, Francis K. L.] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China. [Abraham, Neena S.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Abraham, Neena S.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. [Abraham, Neena S.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Scheiman, James M.] Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI USA. [Laine, Loren] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Chan, FKL (reprint author), Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, 30-32 Ngan Shing St, Shatin, Hong Kong, Peoples R China. RI Hossain, Sarah /C-7332-2009; Chan, Francis K. L./F-4851-2010 OI Hossain, Sarah /0000-0003-1355-0979; Chan, Francis K. L./0000-0001-7388-2436 FU Institute of Digestive Disease, Chinese University of Hong Kong; Asia Pacific offices of AstraZeneca; Pfizer; Eisai; Altana Pharma and Takeda FX This work was funded by an educational grant from the Institute of Digestive Disease, Chinese University of Hong Kong, and supplemented by unrestricted educational funding from the Asia Pacific offices of AstraZeneca, Pfizer, Eisai, Altana Pharma and Takeda. The funders were not involved in the initiation or planning of this consensus meeting, selection of panel members, or drafting, editing or reviewing the manuscript. NR 45 TC 88 Z9 94 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2008 VL 103 IS 11 BP 2908 EP 2918 DI 10.1111/j.1572-0241.2008.02200.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367HU UT WOS:000260543900030 PM 18853980 ER PT J AU Kaplan, GG Jackson, T Sands, BE Frisch, M Andersson, RE Korzenik, J AF Kaplan, Gilaad G. Jackson, Timothy Sands, Bruce E. Frisch, Morten Andersson, Roland E. Korzenik, Joshua TI The Risk of Developing Crohn's Disease After an Appendectomy: A Meta-Analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; ENVIRONMENTAL-FACTORS; ACUTE APPENDICITIS; CLINICAL-COURSE; POPULATION; TONSILLECTOMY; SMOKING; EPIDEMIOLOGY; HYGIENE AB BACKGROUND: Studies exploring the association between appendectomy and Crohn's disease (CD) have reported conflicting findings. We conducted a systematic review of the literature and a meta-analysis to assess the risk of CD following an appendectomy and determine the effect of time between appendectomy and CD diagnosis. METHODS: MEDLINE was used to identify observational studies evaluating the association between appendectomy and CD. Authors were contacted when data were insufficient. Relative risks (RR) with 95% confidence intervals (CI) were calculated using a random effects model. Studies that analyzed their data by the interval between the appendectomy and the diagnosis of CD were assessed separately. The Woolf chi(2) statistic was used to test for homogeneity. Egger's test was used to evaluate publication bias. RESULTS: The summary RR estimate for CD following an appendectomy was significantly elevated (RR 1.61, 95% CI 1.28-2.02), though heterogeneity was observed (P < 0.0001). The risk was elevated within the first year following the operation (RR 6.69, 95% CI 5.42-8.25). The risk of CD was also significantly increased 1-4 yr following an appendectomy (RR 1.99, 95% CI 1.66- 2.38); however, after 5 yr or more, the risk fell to baseline levels (RR 1.08, 95% CI 0.99-1.18). Publication bias was not detected (P = 0.2). CONCLUSION: The meta-analysis demonstrated a significant risk of CD following an appendectomy, though heterogeneity was observed between the studies. The elevated risk early after an appendectomy, which diminishes thereafter, likely reflects diagnostic problems in patients with incipient CD. C1 [Kaplan, Gilaad G.] Univ Calgary, Dept Med, Teaching Res andWellness Ctr, Inflammatory Bowel Dis Clin, Calgary, AB T2N 4N1, Canada. [Jackson, Timothy] McMaster Univ, Dept Surg, Hamilton, ON L8S 4L8, Canada. [Sands, Bruce E.; Korzenik, Joshua] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. [Sands, Bruce E.; Korzenik, Joshua] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Sands, Bruce E.; Korzenik, Joshua] Harvard Univ, Sch Med, Boston, MA USA. [Frisch, Morten] Statens Serum Inst, Dept Epidemiol Res, Div Epidemiol, DK-2300 Copenhagen, Denmark. [Andersson, Roland E.] Cty Hosp Ryhov, Dept Surg, Jonkoping, Sweden. [Andersson, Roland E.] Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden. RP Kaplan, GG (reprint author), Univ Calgary, Dept Med, Teaching Res andWellness Ctr, Inflammatory Bowel Dis Clin, 3280 Hosp Dr NW,Room 6D17, Calgary, AB T2N 4N1, Canada. RI Andersson, Roland/F-3333-2011; Frisch, Morten/E-9206-2016; OI Frisch, Morten/0000-0002-3864-8860; Kaplan, Gilaad/0000-0003-2719-0556 NR 41 TC 44 Z9 45 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2008 VL 103 IS 11 BP 2925 EP 2931 DI 10.1111/j.1572-0241.2008.02118.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367HU UT WOS:000260543900032 PM 18775018 ER PT J AU Rosenberg, PB Mielke, MM Tschanz, J Cook, L Corcoran, C Hayden, KM Norton, M Rabins, PV Green, RC Welsh-Bohmer, KA Breitner, JCS Munger, R Lyketsos, CG AF Rosenberg, P. B. Mielke, M. M. Tschanz, J. Cook, L. Corcoran, Chris Hayden, K. M. Norton, M. Rabins, P. V. Green, R. C. Welsh-Bohmer, K. A. Breitner, J. C. S. Munger, R. Lyketsos, C. G. TI Effects of Cardiovascular Medications on Rate of Functional Decline in Alzheimer Disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Alzheimer disease; risk factors in epidemiology; medications; prognosis ID MILD COGNITIVE IMPAIRMENT; CACHE COUNTY; INCIDENT DEMENTIA; VASCULAR-DISEASE; STATIN THERAPY; BLOOD-PRESSURE; RISK-FACTORS; CHOLESTEROL; PROGRESSION; PREVALENCE AB Background: Evidence suggests that cardiovascular medications, including statins and antihypertensive medications, may delay cognitive decline in patients with Alzheimer dementia (AD). We examined the association of cardiovascular medication use and rate of functional decline in a population-based cohort of individuals with incident AD. Methods: In the Dementia Progression Study of the Cache County Study on Memory, Health, and Aging, 216 individuals with incident AD were identified and followed longitudinally with in-home visits for a mean of 3.0 years and 2.1 follow-up visits. The Clinical Dementia Rating (CDR) was completed at each follow-up. Medication use was inventoried during in-home visits. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) as the outcome and cardiovascular medication use as the major predictors. Results: CDR-Sum increased an average of 1.69 points annually, indicating a steady decline in functioning. After adjustment for demographic variables and the baseline presence of cardiovascular conditions, use of statins (p = 0.03) and beta-blockers (p = 0.04) was associated with a slower annual rate of increase in CDR-Sum (slower rate of functional decline) of 0.75 and 0.68 points respectively, while diuretic use was associated with a faster rate of increase in CDR-Sum (p = 0.01; 0.96 points annually). Use of calcium-channel blockers, angiotensin-converting enzyme inhibitors, digoxin, or nitrates did not affect the rate of functional decline. Conclusions: In this population-based study of individuals with incident AD, use of statins and beta-blockers was associated with delay of functional decline. Further studies are needed to confirm these results and to determine whether treatment with these medications may help delay AD progression. C1 [Rosenberg, P. B.] Johns Hopkins Univ, Sch Med, Div Geriatr Psychiat & Neuropsychiat, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. [Tschanz, J.; Cook, L.; Corcoran, Chris; Norton, M.; Munger, R.] Utah State Univ, Logan, UT 84322 USA. [Hayden, K. M.; Welsh-Bohmer, K. A.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Green, R. C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Breitner, J. C. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Breitner, J. C. S.] Univ Washington, Sch Med, Seattle, WA USA. RP Rosenberg, PB (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Psychiat & Neuropsychiat, Johns Hopkins Bayview Med Ctr, 5300 Alpha Commons Dr,AC4, Baltimore, MD 21224 USA. EM prosenb9@jhmi.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [K08 AG029157, R01 AG011380-08, R01 AG018712, R01 AG018712-03, R01 AG021136, R01 AG021136-05] NR 43 TC 60 Z9 63 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD NOV PY 2008 VL 16 IS 11 BP 883 EP 892 DI 10.1097/JGP.0b013e318181276a PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 367FS UT WOS:000260538500005 PM 18978249 ER PT J AU Wolin, KY Bennett, GG McNeill, LH Sorensen, G Emmons, KM AF Wolin, Kathleen Y. Bennett, Gary G. McNeill, Lorna H. Sorensen, Glorian Emmons, Karen M. TI Low Discretionary Time as a Barrier to Physical Activity and Intervention Uptake SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE physical activity; socioeconomic status; personal barriers ID CULTURAL ACTIVITY PARTICIPATION; HEALTH NETWORK PROJECT; AFRICAN-AMERICAN; WORKING-CLASS; MULTIETHNIC POPULATIONS; CANCER PREVENTION; ACTIVITY QUESTIONNAIRE; DIVERSE SAMPLE; UNITED-STATES; WOMEN AB Objective: To determine whether self-reported discretionary time was associated with physical activity and uptake of a physical activity promotion intervention in a multi-ethnic urban sample. Methods: We examined the association of self-reported discretionary time with hours/week of leisure-time physical activity at baseline and physical activity intervention uptake. Results: Low levels of discretionary time were significantly (P<0.01) associated with fewer hours/week (beta=-0.78, 95%CI= -1.34, -0.22) of physical activity at baseline. Discretionary time was not associated with physical activity intervention uptake. Conclusion: Lack of discretionary time may serve as barrier to physical activity, but its importance on intervention uptake is less clear. C1 [Wolin, Kathleen Y.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Bennett, Gary G.; Sorensen, Glorian; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Dana Farber Canc Inst,Ctr Comunity Based Res, Boston, MA 02115 USA. [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Houston, TX 77030 USA. RP Wolin, KY (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave,Campus Box 8109, St Louis, MO 63110 USA. EM wolink@wustl.edu FU NCI NIH HHS [P01 CA075308, P01 CA075308-01A2] NR 25 TC 5 Z9 5 U1 3 U2 5 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 2008 VL 32 IS 6 BP 563 EP 569 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 369WA UT WOS:000260723400001 PM 18442336 ER PT J AU Stone, R AF Stone, Richard TI Timed sequential induction chemotherapy in AML: Time for reflection SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; HIGH-DOSE CYTARABINE; CYTOSINE-ARABINOSIDE; ADULTS; DAUNORUBICIN; THERAPY; CANCER; TRIAL C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Stone, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM rstone@partners.org NR 15 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2008 VL 83 IS 11 BP 829 EP 830 DI 10.1002/ajh.21288 PG 2 WC Hematology SC Hematology GA 371FW UT WOS:000260818200001 PM 18828158 ER PT J AU Field, JJ Macklin, EA Yan, Y Strunk, RC DeBaun, MR AF Field, Joshua J. Macklin, Eric A. Yan, Yan Strunk, Robert C. DeBaun, Michael R. TI Sibling history of asthma is a risk factor for pain in children with sickle cell anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACUTE CHEST SYNDROME; DISEASE AB The basis of the association between asthma and an increased rate of pain among children with sickle cell anemia (SCA) is unclear. To provide evidence for a familial contribution to this observation, we tested the hypothesis that a family history of asthma is associated with an increased pain rate. Using data from the Cooperative Study for Sickle Cell Disease (CSSCD), we identified 211 children with SCA with asthma history of the parents and siblings. A sibling history of asthma was associated with a greater rate of pain (mean rate ratio = 2.48, 95% CI = 1.6-4.0; P < 0.001) when compared with children without a sibling history of asthma. Parental history of asthma was not associated an increase rate of pain (mean ratio = 1.51, 95% CI = 0.92-2.62; P = 0.12). Further studies are needed to examine genetic and/or environmental risks for asthma as potential contributors to pain in children with SCA. Am. J. Hematol. 83:855-857, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Field, Joshua J.] Washington Univ, Sch Med, Dept Internal Med, Div Hematol, St Louis, MO 63110 USA. [Macklin, Eric A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Biostat Ctr, Boston, MA USA. [Yan, Yan] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Strunk, Robert C.; DeBaun, Michael R.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [DeBaun, Michael R.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [DeBaun, Michael R.] Washington Univ, Sch Med, Dept Biostat, St Louis, MO 63110 USA. RP Field, JJ (reprint author), Washington Univ, Sch Med, Dept Internal Med, Div Hematol, Box 8125,660 S Euclid Ave, St Louis, MO 63110 USA. EM jfield@im.wustl.edu RI Macklin, Eric/E-2955-2013; OI Macklin, Eric/0000-0003-1618-3502; Yan, Yan/0000-0002-5917-1475 FU National Heart, Lung, and Blood Institute [K12 HL08710, HL079937] FX Contract grant sponsor: National Heart, Lung, and Blood Institute; Contract grant numbers: K12 HL08710, HL079937. NR 13 TC 8 Z9 9 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2008 VL 83 IS 11 BP 855 EP 857 DI 10.1002/ajh.21275 PG 3 WC Hematology SC Hematology GA 371FW UT WOS:000260818200008 PM 18819094 ER PT J AU Moran, A Katz, R Jenny, NS Astor, B Bluemke, DA Lima, JAC Siscovick, D Bertoni, AG Shlipak, MG AF Moran, Andrew Katz, Ronit Jenny, Nancy Swords Astor, Brad Bluemke, David A. Lima, Joao A. C. Siscovick, David Bertoni, Alain G. Shlipak, Michael G. TI Left Ventricular Hypertrophy in Mild and Moderate Reduction in Kidney Function Determined Using Cardiac Magnetic Resonance Imaging and Cystatin C: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Kidney disease; cystatin C; glomerular filtration rate; left ventricular hypertrophy; left ventricular mass; magnetic resonance imaging (MRI) ID NUTRITION EXAMINATION SURVEY; GLOMERULAR-FILTRATION-RATE; 3RD NATIONAL-HEALTH; STAGE RENAL-DISEASE; ELDERLY PERSONS; HEART-FAILURE; CARDIOVASCULAR HEALTH; SERUM CREATININE; MORTALITY RISK; UNITED-STATES AB Background: Left ventricular (LV) hypertrophy (LVH) is associated with chronic kidney disease, but the association of LVH with a mild decrease in kidney function is not known. We hypothesized that mild and moderate decreases in kidney function, reflected in greater serum cystatin C concentrations, would be linearly associated with a greater prevalence of LVH. Study Design: Cross-sectional observational study. Settings & Participants: Participants in baseline examinations in the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study with several sites in the United States. Predictors: Cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) and creatinine-based eGFR. Outcomes: LVH and LV mass index. Measurements: Serum cystatin C and creatinine, LV mass obtained by using magnetic resonance imaging. LVH cutoff values for men and women were defined by the upper 95th percentile of LV mass index of all MESA participants without hypertension. Results: Of the 4,971 participants analyzed, mean creatinine-based eGFR was 81 +/- 17 (SD) mL/min/ 1.73 m(2) and mean eGFR(cysC) was 94 +/- 32 mL/min/1.73 m(2). LVH was distinctly more prevalent (> 12%) in only the lowest 2 deciles of eGFR(cysC) (<75 mL/min/1.73 m(2)). When 435 participants (9%) with stage 3 or higher chronic kidney disease (creatinine-based eGFR < 60 mL/min/1.73 m(2)) were excluded, the odds for LVH increased for each lower category of eGFR(cysC) less than 75 mL/min/1.73 m(2): odds ratio 1.6 for LVH with eGFR(cysC) of 60 to 75 mL/min/1.73 m(2) (95% confidence interval, 1.20 to 2.07; P = 0.001), and odds ratio 2.0 for eGFR(cysC) less than 60 mL/min/1.73 m(2) (95% confidence interval, 1.03 to 3.75; P = 0.04) after adjustment for demographic factors, study site, diabetes, and smoking. The association of lower eGFR(cysC); with LVH was attenuated after further adjustment for hypertension. Limitations: Cross-sectional rather than longitudinal design, lack of participants with more advanced kidney disease, lack of a direct measurement of glomerular filtration rate. Conclusions: In participants without chronic kidney disease, eGFRcy c of 75 mL/min/1.73 m(2) or less was associated with a greater odds of LVH. Am J Kidney Dis 52:839-848. (C) 2008 by the National Kidney Foundation, Inc. C1 [Moran, Andrew] Columbia Univ, Dept Med, Div Gen Internal Med, New York, NY USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Jenny, Nancy Swords] Univ Vermont, Dept Pathol, Colchester, VT USA. [Astor, Brad] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Bluemke, David A.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Lima, Joao A. C.] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Bertoni, Alain G.; Shlipak, Michael G.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. RP Shlipak, MG (reprint author), VA Med Ctr 111A1, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95159, N01-HC-95165, N01-HC-95166] FX This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95166 from the National Heart, Lung, and Blood Institute (NHLBI). Dade Behring Inc donated the reagents used to measure cystatin C to MESA and the NHLBI. NR 41 TC 36 Z9 38 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2008 VL 52 IS 5 BP 839 EP 848 DI 10.1053/j.ajkd.2008.06.012 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 367ML UT WOS:000260556000006 PM 18845370 ER PT J AU Foster, MC Keyes, MJ Larson, MG Vita, JA Mitchell, GF Meigs, JB Vasan, RS Benjamin, EJ Fox, CS AF Foster, Meredith C. Keyes, Michelle J. Larson, Martin G. Vita, Joseph A. Mitchell, Gary F. Meigs, James B. Vasan, Ramachandran S. Benjamin, Emelia J. Fox, Caroline S. TI Relations of Measures of Endothelial Function and Kidney Disease: The Framingham Heart Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; brachial reactivity; cystatin C; Framingham Heart Study ID FLOW-MEDIATED DILATION; CHRONIC-RENAL-FAILURE; CARDIOVASCULAR RISK-FACTORS; GLOMERULAR-FILTRATION-RATE; HEMODIALYSIS-PATIENTS; SERUM CREATININE; DEPENDENT DILATION; REACTIVE HYPEREMIA; BRACHIAL-ARTERY; FAMILY-HISTORY AB Background: Endothelial dysfunction is prevalent in individuals with end-stage renal disease. Whether endothelial dysfunction is present in patients with moderate chronic kidney disease (CKD) is uncertain. Study Design: Cross-sectional study. Settings & Participants: Brachial reactivity measurements were obtained during the seventh examination cycle in 2,818 (diameter measurements) and 2,256 (flow measurements) Framingham Heart Study Offspring cohort participants (53% women; mean age, 61 +/- 9 years). Predictor: Estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) derived from creatinine-and cystatin C-based estimating equations; microalbuminuria status. Outcome: Brachial reactivity measurements (baseline brachial diameter, flow-mediated dilation, baseline and hyperemic mean flow). Measurements: Linear regression models were used to model brachial measures as a function of CKD and microalbuminuria status. Results: Overall, 7.3% (n = 206) of participants had CKD, and of 2,301 with urinary measurements, 10.0% (n = 230) had microalbuminuria. Brachial reactivity measures did not differ significantly by CKD status in either creatinine- or cystatin C-based equations in either age- and sex- or multivariable-adjusted models. In age- and sex-adjusted models, microalbuminuria was associated with decreased hyperemic mean flow (47.2 +/- 1.4 versus 51.4 +/- 0.5 mg/g; P = 0.005), but the association was not significant after multivariable adjustment (P = 0.09). Limitations: Predominantly white ambulatory cohort; results may not be generalizable to other ethnic groups or individuals with severe CKD. Conclusions: Endothelial dysfunction was not a major correlate of CKD in our sample. Am J Kidney Dis 52:859-867. (C) 2008 by the National Kidney Foundation, Inc. C1 [Foster, Meredith C.; Keyes, Michelle J.; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Foster, Meredith C.; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Cardiol Sect, Boston, MA 02215 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Vasan, Ramachandran S.] Boston Univ, Prevent Med Sect, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, RO1s HL70100, HL60040, HL076784, AG028321]; National Heart, Lung and Blood Institute, National Institutes of Health [2K24HL04334]; American Diabetes Association Career Development Award; National Center for Research Resources (NCRR) General Clinical Research Centers (GCRC) [M01-RR-01066] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195) and RO1s HL70100, HL60040, HL076784, AG028321 (E.J.B.). Dr Vasan is supported in part by grant 2K24HL04334 from the National Heart, Lung and Blood Institute, National Institutes of Health; American Diabetes Association Career Development Award; and the National Center for Research Resources (NCRR) General Clinical Research Centers (GCRC) grant M01-RR-01066 (J.B.M.). NR 52 TC 13 Z9 13 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2008 VL 52 IS 5 BP 859 EP 867 DI 10.1053/j.ajkd.2008.04.027 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 367ML UT WOS:000260556000008 PM 18617305 ER PT J AU Gaffo, AL Saag, KG AF Gaffo, Angelo L. Saag, Kenneth G. TI Management of Hyperuricemia and Gout in CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE Management; hyperuricemia; gout; chronic kidney disease ID SERUM URIC-ACID; KIDNEY-TRANSPLANT RECIPIENTS; ALLOPURINOL HYPERSENSITIVITY SYNDROME; NUTRITION EXAMINATION SURVEY; XANTHINE-OXIDASE INHIBITOR; RECOMBINANT URATE OXIDASE; STAGE RENAL-DISEASE; 3RD NATIONAL-HEALTH; PURINE-RICH FOODS; DOUBLE-BLIND C1 [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Saag, Kenneth G.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. RP Saag, KG (reprint author), FOT 820,1530 3rd Ave S, Birmingham, AL 35294 USA. EM ksaag@uab.edu NR 135 TC 11 Z9 14 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2008 VL 52 IS 5 BP 994 EP 1009 DI 10.1053/j.ajkd.2008.07.035 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA 367ML UT WOS:000260556000023 PM 18971014 ER PT J AU Jaff, MR AF Jaff, Michael R. TI Venous Thromboembolism 2008: The Changing Paradigm of Deep Vein Thrombosis and Pulmonary Embolism Prophylaxis and Treatment Introduction SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vasc Ctr, 55 Fruit St,Gray Bigelow Suite 800, Boston, MA 02114 USA. EM mjaff@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2008 VL 121 IS 11 SU 1 BP S1 EP S1 DI 10.1016/j.amjmed.2008.08.003 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 364AT UT WOS:000260309300001 ER PT J AU Ablon, SL AF Ablon, Steven L. TI Psychiatry Grand Rounds SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 [Ablon, Steven L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ablon, Steven L.] Harvard Univ, Sch Med, Boston, MA USA. RP Ablon, SL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM slablon@comcast.net NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD NOV PY 2008 VL 108 IS 11 BP 49 EP 49 PG 1 WC Nursing SC Nursing GA 373WR UT WOS:000261004700027 ER PT J AU Stefancyk, AL AF Stefancyk, Amanda L. TI Nurses Participate in Presenting Patients in Morning Rounds SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 Massachusetts Gen Hosp, White 10, Boston, MA 02114 USA. RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, White 10, Boston, MA 02114 USA. EM astefancyk@partners.org NR 0 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD NOV PY 2008 VL 108 IS 11 BP 70 EP 72 PG 3 WC Nursing SC Nursing GA 373WR UT WOS:000261004700030 PM 18946271 ER PT J AU Gee, RE Shacter, HE Kaufman, EJ Long, JA AF Gee, Rebekah E. Shacter, Hannah E. Kaufman, Elinore J. Long, Judith A. TI Behind-the-counter status and availability of emergency contraception SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE behind-the-counter status; contraception availability; emergency contraception ID RANDOMIZED CONTROLLED-TRIAL; CONSCIENTIOUS OBJECTION; ADVANCED PROVISION; ABORTION RATES; ACCESS; PHARMACIES; PREGNANCY; WOMEN AB OBJECTIVE: The objective of the study was to determine whether the 2006 Food and Drug Administration approval of Plan B for behind-the-counter status increased availability. STUDY DESIGN: We conducted a survey in 2005 and 2007 of pharmacies listed in Atlanta, GA, Boston, MA, and Philadelphia, PA. We measured ability to dispense Plan B within 24 hours. Also measured were reasons for lack of availability and cost of Plan B. RESULTS: Pharmacists were interviewed at 1087 pharmacies (75% response rate) in 2005 and 795 pharmacies (82% response rate) in 2007. In 2007, 8% of pharmacies were unable to provide Plan B within 24 hours, compared with 23% of pharmacies in 2005 (P < .001). The total refusal rate in 2007 was half the rate of 2005 (2% vs 4%, P = .004). The average cost of Plan B was $43. CONCLUSION: Availability of Plan B in Atlanta and Philadelphia increased after it was awarded behind-the-counter status. C1 [Gee, Rebekah E.] Univ Penn, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA. [Gee, Rebekah E.; Long, Judith A.] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Sch Med, Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Shacter, Hannah E.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Kaufman, Elinore J.] Harvard Univ, Sch Med, Boston, MA USA. RP Gee, RE (reprint author), 13th Floor Blockley Hall 1303A,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rebe@mail.med.upenn.edu OI Kaufman, Elinore/0000-0001-7550-0024 FU Robert Wood Johnson Clinical Scholars Program FX The authors gratefully acknowledge Zoe Chace and Erica Crane for their help with data collection. The authors thank the Robert Wood Johnson Clinical Scholars Program for funding support. NR 29 TC 5 Z9 5 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2008 VL 199 IS 5 AR 478.e1 DI 10.1016/j.ajog.2008.04.032 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 367XL UT WOS:000260585800011 PM 18554568 ER PT J AU Rodriquez, AA Burns, SP AF Rodriquez, Arthur A. Burns, Stephen P. TI Assessment of Chronic Neck Pain and a Brief Trial of Cervical Strengthening SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Neck Pain; Neck Muscles; Range of Motion; Hyperalgesia ID RANDOMIZED CONTROLLED-TRIAL; WHIPLASH-ASSOCIATED DISORDERS; RESTING HEAD POSTURE; BACK-PAIN; RELIABILITY; DISABILITY; WOMEN; REPEATABILITY; EXCURSION; VALIDITY AB Objective: To determine the relationship among pain, disability, range of motion, isometric strength, and muscle tenderness in persons with chronic nonradicular neck pain and to compare them with healthy controls without neck pain. Design: Cross-sectional study of 30 subjects with and 14 without chronic neck pain. All subjects were administered pain scales, the neck disability index, isometric cervical strength, cervical range of motion, and a quantitated muscle tenderness measure. In addition, an uncontrolled trial of neck strengthening was performed on a subset of 14 subjects with the same outcome variables. Results: Tenderness correlated with pain, neck disability index, and headache in the pain group, and statistically, significantly differed from the subjects without neck pain. Males were stronger than females. Strength was less in the group with neck pain, but did not reach statistical significance. Range of motion was less in the group with pain. Neither range of motion nor strength correlated with neck disability index or pain scores in the neck pain group. in the strengthening trial, strength in left and right rotation significantly improved. Range of motion, pain, and neck disability index changed in a positive direction, but did not reach statistical significance. Muscle tenderness did not change. Conclusions: Muscle tenderness and disability (but not range of motion or muscle strength) is closely related to average pain in the previous week in neck pain subjects. Neck flexor muscle strengthening resulted in positive changes in pain, neck disability index, range of motion, and strength, but not tenderness. C1 [Rodriquez, Arthur A.; Burns, Stephen P.] Univ Washington, Sch Med, Dept Rehabil Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Rodriquez, AA (reprint author), Univ Washington, Sch Med, Dept Rehabil Med, Vet Affairs Puget Sound Hlth Care Syst, C-O Gail Wise Mail Stop 117,1660 S Columbian Way, Seattle, WA 98108 USA. FU Department of Veterans Affairs and the Harborview Injury Prevention and Research Center FX This work was supported by the Department of Veterans Affairs and the Harborview Injury Prevention and Research Center. This article represents the opinion of the authors and does not necessarily represent the Department of Veterans Affairs. NR 30 TC 3 Z9 3 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV PY 2008 VL 87 IS 11 BP 903 EP 909 DI 10.1097/PHM.0b013e318186b05c PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 364MX UT WOS:000260340900005 PM 18787498 ER PT J AU Suri, P Burns, SP Bach, JR AF Suri, Pradeep Burns, Stephen P. Bach, John R. TI Pneumothorax Associated with Mechanical Insufflation-Exsufflation and Related Factors SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Paraplegia-Society CY SEP 06-08, 2005 CL Las Vegas, NV SP Amer Paraplegia Soc DE Insufflation; Pneumothorax; Cough; Adverse Effects; Spinal Cord Injuries ID DUCHENNE MUSCULAR-DYSTROPHY; NEUROMUSCULAR DISEASE; VENTILATION; PROLONGATION; OUTCOMES; LIFE AB Impaired cough that results in ineffective airway secretion clearance is an important contributor to pulmonary complications in patients with neuromuscular weakness including spinal cord injury. Mechanical insufflation-exsufflation (MI-E) is a respiratory aid used by patients with weak respiratory muscles to increase cough peak flows and improve cough effectiveness. Relative contraindications to MI-E are said to include susceptibility to pneumothorax, but the association of pneumothorax with MI-E use has never before been described. We report two cases of pneumothorax in patients with respiratory muscle weakness associated with daily use of MI-E: one was a 58-yr-old male with C4 ASIA C tetraplegia, and the other was a 26-yr-old male with Duchenne muscular dystrophy. Both patients also used positive-pressure ventilatory assistance. Although seemingly rare in this patient population, ventilator users also using MI-E who have increasing dyspnea or who require increasing positive inspiratory pressures when using noninvasive ventilation should be evaluated for pneumothorax. C1 [Suri, Pradeep; Burns, Stephen P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Burns, Stephen P.] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. [Bach, John R.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Suri, P (reprint author), New England Baptist Hosp, Spine Ctr, 125 Parker Hill Ave, Boston, MA 02120 USA. NR 21 TC 15 Z9 18 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV PY 2008 VL 87 IS 11 BP 951 EP 955 DI 10.1097/PHM.0b013e31817c181e PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 364MX UT WOS:000260340900010 PM 18617862 ER PT J AU Lu, FX Chauhan, AK Fernandes, SM Walsh, MT Wagner, DD Davis, AE AF Lu, Fengxin Chauhan, Anil K. Fernandes, Stacey M. Walsh, Meghan T. Wagner, Denisa D. Davis, Alvin E., III TI The effect of C1 inhibitor on intestinal ischemia and reperfusion injury SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE complement inhibition; leukocyte transmigration ID SUPERIOR MESENTERIC-ARTERY; NECROSIS-FACTOR-ALPHA; RAT SMALL-INTESTINE; LEUKOCYTE ADHESION; ESTERASE INHIBITOR; ISCHEMIA/REPERFUSION INJURY; C1-ESTERASE INHIBITOR; HEREDITARY ANGIOEDEMA; RECEPTOR ANTAGONIST; GUT ISCHEMIA AB Complement activation and neutrophil stimulation are two major components in events leading to ischemia and reperfusion (IR) injury. C1 inhibitor (C1INH) inhibits activation of each of the three pathways of complement activation and of the contact system. It is also endowed with anti-inflammatory properties that are independent of protease inhibition. The goal of these studies was to investigate the role and mechanism of C1INH in alleviating IR-induced intestinal injury. C57BL/6, C1INH-deficient (C1INH(-/-)), bradykinin type 2 receptor-deficient (Bk2R(-/-)), and C3-deficient mice (C3(-/-)) were randomized into three groups: sham operated control, IR, and IR + C1INH-treated groups. Ischemia was generated by occlusion of the superior mesenteric artery followed by reperfusion. C1INH or reactive center-cleaved inactive C1INH (iC1INH) was injected intravenously before reperfusion. IR resulted in intestinal injury in C57BL/6, C1INH(-/-), Bk2R(-/-), and C3(-/-) mice with significantly increased neutrophil infiltration into intestinal tissue. In each mouse strain, C1INH treatment reduced intestinal tissue injury and attenuated leukocyte infiltration compared with the untreated IR group. C1INH inhibited leukocyte rolling in the mesenteric veins of both C57BL/6 and C3-deficient mice subjected to IR. C1INH treatment also improved the survival rate of C57BL/6 and C1INH(-/-) mice following IR. Similar findings were observed in the IR animals treated with iC1INH. These studies emphasize the therapeutic benefit of C1INH in preventing intestinal injury caused by IR. In addition to the protective activities mediated via inhibition of the complement system, these studies indicate that C1INH also plays a direct role in suppression of leukocyte transmigration into reperfused tissue. C1 [Lu, Fengxin; Chauhan, Anil K.; Fernandes, Stacey M.; Walsh, Meghan T.; Wagner, Denisa D.; Davis, Alvin E., III] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Chauhan, Anil K.; Walsh, Meghan T.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lu, FX (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM fengxin@idi.harvard.edu NR 52 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 2008 VL 295 IS 5 BP G1042 EP G1049 DI 10.1152/ajpgi.90460.2008 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 369DO UT WOS:000260674700018 PM 18787060 ER PT J AU Al-Noori, S Sanders, NM Taborsky, GJ Wilkinson, CW Zavosh, A West, C Sanders, CM Figlewicz, DP AF Al-Noori, Salwa Sanders, Nicole M. Taborsky, Gerald J., Jr. Wilkinson, Charles W. Zavosh, Aryana West, Connie Sanders, Colleen M. Figlewicz, Dianne P. TI Recurrent hypoglycemia alters hypothalamic expression of the regulatory proteins FosB and synaptophysin SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE FosB; recurrent hypoglycemia; paraventricular nucleus; corticotropinreleasing factor; synaptophysin ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENOCORTICAL AXIS; NEUROPEPTIDE GENE-EXPRESSION; PARAVENTRICULAR NUCLEUS; RAT HYPOTHALAMUS; DIFFERENTIAL REGULATION; NEURONAL PLASTICITY; STRESS INTEGRATION; REPEATED RESTRAINT; AUTONOMIC FAILURE AB A limiting factor to the clinical management of diabetes is iatrogenic hypoglycemia. With multiple hypoglycemic episodes, the collective neuroendocrine response that restores euglycemia is impaired. In our animal model of recurrent hypoglycemia (RH), neuroendocrine deficits are accompanied by a decrease in medial hypothalamic activation. Here we tested the hypothesis that the medial hypothalamus may exhibit unique changes in the expression of regulatory proteins in response to RH. We report that expression of the immediate early gene FosB is increased in medial hypothalamic nuclei, anterior hypothalamus, and posterior paraventricular nucleus of the thalamus (THPVN) of the thalamus following RH. We identified the hypothalamic PVN, a key autonomic output site, among the regions expressing FosB. To identify the subtype(s) of neuronal populations that express FosB, we screened candidate neuropeptides of the PVN for coexpression using dual fluorescence immunohistochemistry. Among the neuropeptides analyzed [including oxytocin, vasopressin, thyrotropin-releasing hormone, and corticotropin-releasing factor (CRF)], FosB was only identified in CRF-positive neurons. Inhibitory gamma-aminobutyric acidpositive processes appear to impinge on these FosB-expressing neurons. Finally, we observed a significant decrease in the presynaptic marker synaptophysin within the PVN of RH-treated vs. saline-treated rats, suggesting that rapid alterations of synaptic morphology may occur in association with RH. Collectively, these data suggest that RH stress triggers cellular changes that support synaptic plasticity, in specific neuroanatomical sites, which may contribute to the development of hypoglycemia-associated autonomic failure. C1 [Al-Noori, Salwa; Sanders, Nicole M.; Wilkinson, Charles W.; Zavosh, Aryana; Figlewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Taborsky, Gerald J., Jr.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Sanders, Nicole M.; Taborsky, Gerald J., Jr.; West, Connie; Figlewicz, Dianne P.] Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA USA. [Wilkinson, Charles W.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Al-Noori, S (reprint author), VA Puget Sound Hlth Care Syst, Metab Endocrinol 151,1660 So Columbian Way, Seattle, WA 98108 USA. EM saan@u.washington.edu FU Department of Veterans Affairs (VA); National Institute of Diabetes and Digestive and Kidney Diseases [R21-062446, DK-40963, 2 R01 DK-050154-09A1] FX These studies were supported by the Department of Veterans Affairs (VA) Merit Review Program and Research Career Scientist (D. P. Figlewicz Lattemann), the VA Merit Review Entry Program (N. Sanders), and VA support to G. J. Taborsky and C. Wilkinson and by National Institute of Diabetes and Digestive and Kidney Diseases Grants R21-062446 and DK-40963 (S. Al-Noori) and 2 R01 DK-050154-09A1. NR 61 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2008 VL 295 IS 5 BP R1446 EP R1454 DI 10.1152/ajpregu.90511.2008 PG 9 WC Physiology SC Physiology GA 368DB UT WOS:000260600400011 PM 18753263 ER PT J AU Miller, YE AF Miller, York E. TI Minimizing Unintended Consequences of Detecting Lung Nodules by Computed Tomography SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID CANCER; GUIDELINES; PROJECT; ASSAY; CT C1 [Miller, York E.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Miller, York E.] Univ Colorado, Denver, CO 80202 USA. RP Miller, YE (reprint author), Denver Vet Affairs Med Ctr, Denver, CO USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2008 VL 178 IS 9 BP 891 EP 892 DI 10.1164/rccm.200808-1257ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 368HG UT WOS:000260611600003 PM 18945870 ER PT J AU Pandharipande, PV Harisinghani, MG Ozanne, EM Specht, MC Hur, C Lee, JM Gazelle, GS AF Pandharipande, Pari V. Harisinghani, Mukesh G. Ozanne, Elissa M. Specht, Michelle C. Hur, Chin Lee, Janie M. Gazelle, G. Scott TI Staging MR Lymphangiography of the Axilla for Early Breast Cancer: Cost-Effectiveness Analysis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; cost-effectiveness analysis; MR lymphangiography; sentinel lymph node biopsy ID LYMPH-NODE METASTASES; POSITRON-EMISSION-TOMOGRAPHY; HEALTH-STATE PREFERENCES; RANDOMIZED-TRIALS; CONVENIENT APPROXIMATION; POSTMENOPAUSAL WOMEN; LIFE EXPECTANCY; DISSECTION; BIOPSY; IMPACT AB OBJECTIVE. The purpose of this study was to compare the cost-effectiveness of MR lymphangiography-based strategies with that of sentinel lymph node (SLN) biopsy alone in the axillary staging of early breast cancer. MATERIALS AND METHODS. A decision-analytic Markov Model was developed to estimate quality-adjusted life expectancy and lifetime costs among 61-year-old women with clinically node-negative early breast cancer. Three axillary staging strategies were compared: MR lymphangiography alone, combined MR lymphangiography-SLN biopsy, and SLN biopsy alone. The model incorporated treatment decisions, outcome, and costs consequent to axillary staging results. An incremental cost-effectiveness analysis was performed to compare strategies. The effect of changes in key parameters on results was addressed in sensitivity analysis. RESULTS. In the base-case analysis, combined MR lymphangiography-SLN biopsy was associated with the highest quality-adjusted life expectancy (13.970 years) and cost ($ 63,582), followed by SLN biopsy alone (13.958 years, $ 62,462) and MR lymphangiography alone (13.957 years, $ 61,605). MR lymphangiography-SLN biopsy and SLN biopsy both were associated with higher life expectancy and cost relative to those of MR lymphangiography. MR lymphangiography-SLN biopsy, however, was associated with greater overall life expectancy and greater added life expectancy per dollar than was SLN biopsy. SLN biopsy alone therefore was not considered cost-effective, but MR lymphangiography and MR lymphangiography-SLN biopsy remained competing choices. Preference of MR lymphangiography strategies was most dependent on the sensitivity of MR lymphangiography and SLN biopsy and on the quality-of-life consequences of SLN biopsy and axillary lymph node dissection, but otherwise was stable across most parameter ranges tested. CONCLUSION. From a cost-effectiveness perspective, MR lymphangiography strategies for axillary staging of early breast cancer are preferred over SLN biopsy alone. The sensitivity of MR lymphangiography is a critical determinant of the cost-effectiveness of MR lymphangiography strategies and merits further investigation in the care of patients with early breast cancer. C1 [Pandharipande, Pari V.; Ozanne, Elissa M.; Lee, Janie M.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA 02114 USA. [Pandharipande, Pari V.; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Gastrointestinal Unit, Boston, MA 02114 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, 101 Merrimac St,10th Fl, Boston, MA 02114 USA. OI Hur, Chin/0000-0002-2819-7576 FU National Institutes of Health (NIH) [R25 CA 92203] FX Supported by National Institutes of Health (NIH) R25 CA 92203 training grant (Program for Cancer Outcomes Research Training, G. S. Gazelle, principal investigator; P. V. Pandharipande, trainee, 2004-2006). NR 59 TC 12 Z9 12 U1 1 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2008 VL 191 IS 5 BP 1308 EP 1319 DI 10.2214/AJR.07.3861 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363DQ UT WOS:000260246700004 PM 18941062 ER PT J AU Saokar, A Arellano, RS Gervais, DA Mueller, PR Hahn, PF Lee, SI AF Saokar, Anuradha Arellano, Ronald S. Gervais, Debra A. Mueller, Peter R. Hahn, Peter F. Lee, Susanna I. TI Transvaginal Drainage of Pelvic Fluid Collections: Results, Expectations, and Experience SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE drainage; pelvis; transvaginal sonography ID SONOGRAPHICALLY GUIDED ASPIRATION; 250 ABDOMINAL ABSCESSES; OVARIAN CYSTS; PERCUTANEOUS DRAINAGE; TUBOOVARIAN-ABSCESS; ULTRASOUND; MANAGEMENT; GUIDANCE AB OBJECTIVE. The purpose of this study was to review our 13-year experience with sonographically guided transvaginal drainage procedures in terms of type of transvaginal procedure, that is, aspiration or catheter drainage, complication rate, and long-term success. MATERIALS and METHODS. A search of an interventional radiology database identified 85 transvaginal drainage procedures on 67 patients. Pertinent medical records and images were reviewed. Clinical success was defined as no need for surgery. RESULTS. The mean follow-up period was 36.6 months (range, 7 days-132 months). Forty-five aspiration and 40 catheter drainage procedures were performed on 67 patients. Indications for the procedures included postoperative fluid collection (n = 25), tuboovarian abscess unresponsive to medical therapy (n = 17), symptomatic ovarian cyst (n = 17), and miscellaneous causes (n = 8). Clinical success was achieved in 50 of 67 cases (75%), including all cases of 25 postoperative fluid collection, 12 of 17 tuboovarian abscesses (71%), and seven of 17 ovarian cysts (41%). No complications were found in patients who underwent aspiration alone. The following minor complications occurred in patients who underwent catheter drainage: two cases of bladder transgression, one case of infection, and one case of catheter-related pain. Premature dislodgment of the catheter was an issue for four of 40 patients (10%). CONCLUSION. Postoperative fluid collections can be managed with a high rate of success by means of transvaginal aspiration or catheter drainage. Transvaginal catheter drainage is an alternative to surgery in the management of tuboovarian abscesses unresponsive to medical management. Aspiration alone is sufficient to drain ovarian cysts and provide symptomatic relief. Most cysts recur, however, ultimately necessitating surgery. Aspiration is safe, but catheter drainage is associated with a 10% rate of minor complications. C1 [Saokar, Anuradha; Arellano, Ronald S.; Gervais, Debra A.; Mueller, Peter R.; Hahn, Peter F.; Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Saokar, A (reprint author), Boston Med Ctr, Dept Radiol, 820 Harrison Ave,FGH Bldg 3rd Fl, Boston, MA 02118 USA. NR 36 TC 9 Z9 11 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2008 VL 191 IS 5 BP 1352 EP 1358 DI 10.2214/AJR.07.3808 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363DQ UT WOS:000260246700010 PM 18941068 ER PT J AU Kozanek, M Van de Velde, SK Gill, TJ Li, GA AF Kozanek, Michal Van de Velde, Samuel K. Gill, Thomas J. Li, Guoan TI The Contralateral Knee Joint in Cruciate Ligament Deficiency SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE cruciate ligament; knee kinematics; contralateral knee; imaging ID IN-VIVO KINEMATICS; INSTRUMENTED MEASUREMENT; MRI ANALYSIS; ANTERIOR; FLEXION; LAXITY; ANTEROPOSTERIOR; RECONSTRUCTION; ROTATION; MOTION AB Background: Patients with unilateral ligament deficiency are believed to have altered kinematics of the contralateral knee, increasing the risk of contralateral joint injury. Therefore, the contralateral knees might not be a reliable normal kinematic control. Purpose: To compare the in vivo kinematics of the uninjured contralateral knees of patients with anterior or posterior cruciate ligament deficiency with knee kinematics of age-matched patients without joint injury. Study Design: Controlled laboratory study. Methods: Ten subjects with bilateral healthy knees, 10 patients with acute unilateral anterior cruciate ligament injury, and 10 with acute unilateral posterior cruciate ligament injury participated in this study. Kinematics were measured from 0 degrees to 90 degrees of flexion using imaging and 3-dimensional modeling. Results: No significant differences were found across the groups in all rotations and translations during weightbearing flexion (P > .9). Conclusion: Patients with unilateral cruciate ligament deficiency did not alter kinematics of the contralateral uninjured knee during weightbearing flexion. In addition, these findings suggest that the included patients with anterior cruciate ligament or posterior cruciate ligament deficiency did not have preexisting abnormal kinematics of the knee. Clinical Relevance: As the contralateral joint kinematics of the injured patients were not affected by the ipsilateral ligament injury in the short term, physicians and researchers might use the contralateral knee as a reliable normal kinematic control. C1 [Li, Guoan] Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, GRJ 1215,55 Fruit St, Boston, MA 02114 USA. EM gli1@partners.org FU National Institute of Health [R01 AR052408, R21 AR051078]; Department of Orthopaedic Surgery at Massachusetts General Hospital FX The authors gratefully acknowledge the patients and subjects who participated in this study. The authors also acknowledge the financial support of the National Institute of Health (R01 AR052408, R21 AR051078) and the Department of Orthopaedic Surgery at Massachusetts General Hospital. NR 22 TC 17 Z9 17 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD NOV PY 2008 VL 36 IS 11 BP 2151 EP 2157 DI 10.1177/0363546508319051 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 367CP UT WOS:000260530400010 PM 18625804 ER PT J AU Longo, WE Itani, K Tarpley, J Kozol, RA AF Longo, Walter E. Itani, Kamal Tarpley, John Kozol, Robert A. TI Association of VA Surgeons annual resident paper award winners: career paths following completion of postgraduate training SO AMERICAN JOURNAL OF SURGERY LA English DT Editorial Material DE Award; Academic; Scientific presentation; Trainee; Organization AB The aims of this study are to track those AVAS podium resident prize winners and to determine patterns of fellowship training type of practice, and primary area of specialization and whether their prize winning paper reflects their current area of specialization today. We also determined whether these residents, once completing their training, ever practiced at a VA hospital, and, whether they have been or currently are members of the AVAS. There have been 43 residents who have won 46 podium awards during this 18 year period. Three/46 (6%) awards were won by a resident twice during different years. Among the 42 locatable residents, 3/42 (7%) are still in surgery training. Among those 39 who are in practice, 30/39 (76%) undertook a clinical fellowship and 22/39 (56%) are in an academic setting. Only 3/39 (8%) has ever worked at a VA hospital; all 3 are currently members of the AVAS. Among those with a specific area of clinical or research specialization (n = 32), in 25/32 (78%), their paper reflects their current area of specialization. Among our cohort of annual AVAS resident prize winners most have taken fellowship training. Greater than 50% pursue academic practice. Among those with an area of specialization, their prize winning paper reflects on their current area of specialization today. Few have ever worked in a VA hospital and thus few have ever been members of the AVAS. (C) 2008 Elsevier Inc. All rights reserved. C1 [Longo, Walter E.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Itani, Kamal] VA Boston Hlth Care Syst, Dept Surg, Boston, MA USA. [Itani, Kamal] Boston Univ, Sch Med, Boston, MA 02118 USA. [Tarpley, John] Tennessee Valley VA Hlth Care Syst, Dept Surg, Nashville, TN USA. [Tarpley, John] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Kozol, Robert A.] Univ Connecticut, Sch Med, Dept Surg, Farmington, CT 06032 USA. RP Longo, WE (reprint author), Yale Univ, Sch Med, Dept Surg, LH 118, New Haven, CT 06510 USA. EM walter.longo@yale.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2008 VL 196 IS 5 BP 621 EP 622 DI 10.1016/j.amjsurg.2008.08.002 PG 2 WC Surgery SC Surgery GA 368WK UT WOS:000260653200001 PM 18954595 ER PT J AU Ebaugh, JL Gagnon, D Owens, CD Conte, MS Raffetto, JD AF Ebaugh, James L. Gagnon, David Owens, Christopher D. Conte, Michaels S. Raffetto, Joseph D. TI Comparison of costs of staged versus simultaneous lower extremity arterial hybrid procedures SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Surgical Symposium CY MAY 04-06, 2008 CL Dallas, TX DE Hybrid; Healthcare costs; Utilization; Vascular surgery; Percutaneous transluminal angioplasty and stent; Lower extremity bypass ID OCCLUSIVE DISEASE; UNITED-STATES; ENDARTERECTOMY; ANGIOPLASTY; THERAPY; RATES AB BACKGROUND: Hybrid procedures combine endovascular and open surgical techniques. We examined utilization rates and ways of performing them more efficiently. METHODS: Hybrids were selected using codes for femoral endarterectomy, infrainguinal, or aortoiliac-femoral bypass and angioplasty from Nationwide Inpatient Sample (NIS) data, then categorized as staged, or performed on the same day. Outcomes included utilization rates, total hospital charges, and length of stay (LOS). Confounders of charges and LOS were identified and excluded from final comparisons. RESULTS: Utilization increased 7% from 2000 to 2004. Univariate associations linked staging to variables included in linear regressions for hospital charges and LOS. Excluding identified confounders from the final subgroup analysis still showed large differences in charges (same-day = $34,206, staged = $60,087) and LOS (same-day = 3 days, staged = 7 days). CONCLUSIONS: Utilization of hybrids is increasing. Performing hybrids on the same day, if possible, greatly reduces hospital charges and LOS, emphasizing preadmission planning and simultaneous coordination of both portions. Published by Elsevier Inc. C1 [Ebaugh, James L.; Owens, Christopher D.; Raffetto, Joseph D.] Boston VA Healthcare Syst, Surg Serv 112, W Roxbury, MA 02132 USA. [Ebaugh, James L.; Owens, Christopher D.; Conte, Michaels S.; Raffetto, Joseph D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Gagnon, David] VA Cooperat Studies Program, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gagnon, David] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Ebaugh, JL (reprint author), Boston VA Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM james.ebaugh2@med.va.gov NR 20 TC 20 Z9 23 U1 1 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2008 VL 196 IS 5 BP 634 EP 640 DI 10.1016/j.amjsurg.2008.08.003 PG 7 WC Surgery SC Surgery GA 368WK UT WOS:000260653200004 PM 18954597 ER PT J AU Chu, D Bakaeen, FG Wang, XL LeMaire, SA Coselli, JS Huh, J AF Chu, Danny Bakaeen, Faisal G. Wang, Xing Li LeMaire, Scott A. Coselli, Joseph S. Huh, Joseph TI Does the duration of surgery affect outcomes in patients undergoing coronary artery bypass grafting? SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Surgical Symposium CY MAY 04-06, 2008 CL Dallas, TX DE Coronary artery bypass grafting; Duration of surgery; Outcomes ID CARDIAC-SURGERY; DETERMINANTS; MORTALITY; STAY; CARE AB BACKGROUND: Numerous predictors of coronary artery bypass grafting (CABG) outcomes have been identified. We aimed to determine whether the duration of surgery independently predicts outcome in patients undergoing CABG. METHODS: We retrospectively reviewed data from 337 patients (mean age 62 +/- 7 years) who underwent CABG consecutively at our institution between January 2005 and December 2006. RESULTS: Duration of surgery correlated positively with length of both surgical intensive care unit (SICU) stay (r = .147, P = .004) and ventilator support (r = .097, P = .038) in univariate analysis, but only with length of SICU stay (P = .01) in a multivariate logistic regression after confounding factors were controlled for in the model. The regression coefficient was .006; every additional 30 minutes of surgery time was associated with 4.32 more hours of SICU stay. Duration of surgery was not associated with survival (P > .05). CONCLUSIONS: Although duration of surgery did not affect short-term survival after CABG, surgical duration independently predicted length of SICU stays. Efforts to reduce the length of operations may promote more efficient use of hospital resources. Published by Elsevier Inc. C1 [Chu, Danny; Bakaeen, Faisal G.; Wang, Xing Li; LeMaire, Scott A.; Coselli, Joseph S.; Huh, Joseph] Baylor Coll Med, Div Cardiothorac Surg, Houston, TX 77030 USA. [Chu, Danny; Bakaeen, Faisal G.; Huh, Joseph] Michael E DeBakey Vet Affairs Med Ctr, Operat Care Line, Houston, TX USA. [Wang, Xing Li; LeMaire, Scott A.; Coselli, Joseph S.] St Lukes Episcopal Hosp, Texas Heart Inst, Sect Adult Cardiac Surg, Houston, TX USA. RP Chu, D (reprint author), Baylor Coll Med, Div Cardiothorac Surg, Houston, TX 77030 USA. EM dchumd@gmail.com NR 14 TC 6 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2008 VL 196 IS 5 BP 652 EP 656 DI 10.1016/j.amjsurg.2008.07.003 PG 5 WC Surgery SC Surgery GA 368WK UT WOS:000260653200007 PM 18778805 ER PT J AU Robinson, TN Raeburn, CD Angles, EM Moss, M AF Robinson, Thomas N. Raeburn, Christopher D. Angles, Erik M. Moss, Marc TI Low tryptophan levels are associated with postoperative delirium in the elderly SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Surgical Symposium CY MAY 04-06, 2008 CL Dallas, TX DE Tryptophan; Delirium; Surgery; Postoperative; Geriatric ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL; AMINO-ACIDS; PLASMA; VALIDATION; DEMENTIA; SURGERY AB BACKGROUND: Postoperative delirium is a common complication in geriatric patients. Tryptophan is an amino acid precursor to the mood-stabilizing neurotransmitters serotonin and melatonin. We hypothesized that tryptophan levels are lower in elderly subjects who develop postoperative delirium. METHODS: A prospective observational study was performed. Subjects older than 50 years undergoing surgery with an anticipated postoperative intensive care unit admission were recruited. Postoperative delirium assessment occurred daily using the Confusion Assessment Method-intensive care unit. Peripheral serum tryptophan levels were measured 2 days after surgery. RESULTS: Forty-nine subjects (46 men) were enrolled, with an average age of 64 7 years. The incidence of delirium was 43% (21 of 49). The average duration of delirium was 2.9 +/- 3.0 days. Tryptophan levels were lower in the subjects who developed delirium (29.9 +/- 13.3 vs 48.5 +/- 19.8 mu g/mL; P = .001). CONCLUSIONS: Lower levels of tryptophan postoperatively were associated with the development of delirium in the elderly. Published by Elsevier Inc. C1 [Robinson, Thomas N.; Raeburn, Christopher D.; Angles, Erik M.] Univ Colorado, Hlth Sci Ctr, Dept Surg, Aurora, CO 80045 USA. [Moss, Marc] Univ Colorado, Hlth Sci Ctr, Dept Med, Aurora, CO 80045 USA. [Robinson, Thomas N.; Raeburn, Christopher D.; Angles, Erik M.] Denver Vet Affairs Med Ctr, Dept Surg, Denver, CO USA. RP Robinson, TN (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Surg, 12631 E 17th Ave,Mail Stop C313,POB 6511, Aurora, CO 80045 USA. EM thomas.robinson@uchsc.edu FU NHLBI NIH HHS [K24 HL089223, K24 HL089223-02, K24-HL-089,223] NR 18 TC 21 Z9 22 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2008 VL 196 IS 5 BP 670 EP 674 DI 10.1016/j.amjsurg.2008.07.007 PG 5 WC Surgery SC Surgery GA 368WK UT WOS:000260653200010 PM 18789427 ER PT J AU Rousou, LI Crittenden, MD Taylor, KB Healey, NA Gibson, S Thatte, HS Hairne, M Khuri, SF AF Rousou, Laki I. Crittenden, Michael D. Taylor, Kristin B. Healey, Nancy A. Gibson, Stephen Thatte, Hemant S. Hairne, Miguel Khuri, Shukri F. TI Troponin I after cardiac surgery and its implications on myocardial protection, outcomes, and cost SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Surgical Symposium CY MAY 04-06, 2008 CL Dallas, TX DE Cardiac surgery; Cardiac enzymes; Myocardial protection; Myocardial tissue pH; Outcomes; Cost ID ARTERY BYPASS-SURGERY; LONG-TERM SURVIVAL; IMPROVEMENT; INFARCTION; ACIDOSIS; LENGTH; STAY; PH AB BACKGROUND: Myocardial acidosis during cardiac surgery and postoperative troponin I are markers of myocardial damage that have been shown to predict adverse outcomes. We investigated the relationship between troponin I and myocardial tissue pH, patient outcomes, and cost. METHODS: Data were prospectively collected on 205 cardiac surgery patients. Troponin I was sampled upon arrival to the intensive care unit (ICU) and every 6 hours thereafter for 24 hours. The lowest pH encountered during aortic cross clamp (LpH) was related to postoperative troponin I on the multivariate level. Multivariate models were constructed to predict adverse events (AE) and cost. RESULTS: LpH was an independent inverse determinant of postoperative troponin I (P = .0067). Troponin I and its interaction with LpH were multivariate predictors of AE (P = .0012; .0001;odds ratio = 6.9, 10.2, respectively). Troponin I independently predicts surgical ICU (SICU) cost (P = .0256). CONCLUSION: Postoperative troponin I elevation reflects intraoperative myocardial acidosis and damage. The strong relationship between troponin 1, AE, and cost indicates the damage incurred is clinically and economically relevant. Strategies to ameliorate intraoperative myocardial tissue acidosis will decrease troponin I release, subsequent AE, and associated costs. Published by Elsevier Inc. C1 [Rousou, Laki I.; Crittenden, Michael D.; Taylor, Kristin B.; Healey, Nancy A.; Gibson, Stephen; Thatte, Hemant S.; Hairne, Miguel; Khuri, Shukri F.] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Rousou, Laki I.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Rousou, Laki I.; Crittenden, Michael D.; Thatte, Hemant S.; Hairne, Miguel; Khuri, Shukri F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Crittenden, Michael D.; Thatte, Hemant S.; Hairne, Miguel; Khuri, Shukri F.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Healey, NA (reprint author), VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. EM nancy.healey@va.gov NR 25 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2008 VL 196 IS 5 BP 703 EP 709 DI 10.1016/j.amjsurg.2008.07.002 PG 7 WC Surgery SC Surgery GA 368WK UT WOS:000260653200015 PM 18789416 ER PT J AU Dhaliwal, AS Chu, D Deswal, A Bozkurt, B Coselli, JS LeMaire, SA Huh, J Bakaeen, FG AF Dhaliwal, Arnandeep S. Chu, Danny Deswal, Anita Bozkurt, Biykern Coselli, Joseph S. LeMaire, Scott A. Huh, Joseph Bakaeen, FaisaL G. TI The July effect and cardiac surgery: the effect of the beginning of the academic cycle on outcomes SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Surgical Symposium CY MAY 04-06, 2008 CL Dallas, TX DE Cardiac surgery; July effect; Morbidity; Mortality; Outcomes; Seasonal effects ID SEASONAL-VARIATION; TEACHING HOSPITALS; HEART-DISEASE; MORTALITY; CORONARY; IMPACT; RISK; TEMPERATURE; IMPROVEMENT; RESIDENT AB BACKGROUND: The effect of the time of the academic year on cardiac surgical outcomes is unknown. METHODS: Using prospectively collected data, we identified all (n = 1,673) cardiac surgical procedures performed at our institution between October 1997 and April 2007. Morbidity and mortality rates were compared between 2 periods of the academic year, one early (July I-August 31, n = 242) and one later in the year (September 1-June 30, n = 1,431). A prediction model was constructed by using stepwise logistic regression modeling. RESULTS: Morbidity rates did not differ significantly between the early (12.8%) and later periods (15.4%) (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.54-1.28; P = 0.3). Additionally, there was no significant difference in operative mortality between the early (1.2%) and later periods (3.5%) (OR, 0.28; 95% CI, 0.07-1.19; P = 0.06). CONCLUSIONS: The early and later parts of the academic year were associated with similar risk-adjusted outcomes. Further studies are needed to determine whether our findings are applicable to other academic cardiac centers. Published by Elsevier Inc. C1 [Chu, Danny; Coselli, Joseph S.; LeMaire, Scott A.; Huh, Joseph; Bakaeen, FaisaL G.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. [Dhaliwal, Arnandeep S.; Deswal, Anita; Bozkurt, Biykern] Baylor Coll Med, Dept Med, Div Cardiol, Houston, TX 77030 USA. [Chu, Danny; Deswal, Anita; Bozkurt, Biykern; Huh, Joseph; Bakaeen, FaisaL G.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Coselli, Joseph S.; LeMaire, Scott A.] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. RP Bakaeen, FG (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 23 TC 22 Z9 22 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2008 VL 196 IS 5 BP 720 EP 725 DI 10.1016/j.amjsurg.2008.07.005 PG 6 WC Surgery SC Surgery GA 368WK UT WOS:000260653200018 PM 18789415 ER PT J AU Rahemtullah, A Longtine, JA Harris, NL Dorn, M Zembowicz, A Quintanilla-Fend, L Preffer, FI Ferry, JA AF Rahemtullah, Aliyah Longtine, Janina A. Harris, Nancy Lee Dorn, Michelle Zembowicz, Artur Quintanilla-Fend, Leticia Preffer, Frederic I. Ferry, Judith A. TI CD20(+) T-cell Lymphoma Clinicopathologic Analysis of 9 Cases and a Review of the Literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE T-cell lymphoma; CD20; mycosis fungoides; enteropathy; CD30; Epstein-Barr virus; rituximab ID NON-HODGKINS-LYMPHOMA; RECEPTOR GENE REARRANGEMENTS; MONOCLONAL-ANTIBODY L26; B-CELL; LOW-LEVEL; EXPRESSION; LEUKEMIA; ANTIGEN; LYMPHOCYTES; PHENOTYPE AB Rare cases of CD20(+) T-cell lymphoma (TCL) have been reported, but the clinicopathologic spectrum of this disorder is not known. We identified 9 cases of CD20(+) TCL diagnosed at Our institution and 26 additional cases through a search of the English language literature. Among current cases, there were 7 men (ages 71 to 8 1, median 75 y) and 2 women (ages 36 and 37 y). Five patients presented with predominantly nodal disease (localized in 3 and widespread in 2 cases) and 4 patients presented with purely extranodal disease involving the parotid glands, skin, or small intestine. CD20 was uniformly and strongly expressed in 5 cases and dimly expressed or present on a Subset of neoplastic cells in 4 cases. The proportion of CD20(+) T cells changed over time in 3 cases. Three cases fulfilled diagnostic criteria for clinicopathologically defined Subtypes of TCL (2 mycosis fungoides; 1 enteropathy-type TCL), whereas 6 were peripheral TCL unspecified with variable cytomorphology, T-cell immunophenotype, and sites of involvement. In 8 of 9 cases, a clonal T-cell Population was identified by molecular genetic analysis. Among 8 cases with clinical follow-up, 5 behaved aggressively with death from disease within 3 years of diagnosis in 4 cases (median Survival: 11 mo, range: 1 to 35 mo), and recurrent disease at 10 months in 1 cased 1 patient died of an EBV+ B-cell lymphoma (BCL) 66 months after the original diagnosis; in the remaining 2 cases, patients were alive and undergoing treatment (Follow-up: 4 and 18 mo). Historical cases showed similar clinicopathologic variability. CD20(+) TCL is rare, and clinically and pathologically heterogeneous. When CD20 expression is present in TCL, it may be dimmer than that of normal B cells, suggesting neoplastic transformation of a normal CD20dim(+) T-cell Subset. Cases of CD20(+) TCL in which the proportion of CD20(+) cells changes over time may reflect aberrant expression of CD20, possibly as in activation marker, by neoplastic T cells. CD20(+) TCL may cause diagnostic difficulty, particularly in cases that clinically and pathologically mimic BCL. Knowledge of the unusual phenomenon of CD20 expression in TCL, in conjunction with careful morphologic analysis, the use of a panel of antibodies, and molecular genetic Studies, is important in avoiding a misdiagnosis of BCL. C1 [Rahemtullah, Aliyah] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Rahemtullah, Aliyah; Longtine, Janina A.; Harris, Nancy Lee; Dorn, Michelle; Zembowicz, Artur; Preffer, Frederic I.; Ferry, Judith A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Longtine, Janina A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Quintanilla-Fend, Leticia] GSF Natl Res Ctr Environm & Hlth, Inst Pathol, Neuherberg, Germany. RP Rahemtullah, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arahemtullah@partners.org NR 48 TC 41 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2008 VL 32 IS 11 BP 1593 EP 1607 DI 10.1097/PAS.0b013e31817d7452 PG 15 WC Pathology; Surgery SC Pathology; Surgery GA 369PB UT WOS:000260705300001 PM 18753947 ER PT J AU Ruangchira-Urai, R Colby, TV Klein, J Nielsen, GP Kradin, RL Mark, EJ AF Ruangchira-Urai, Ruchira Colby, Thomas V. Klein, Julianne Nielsen, G. Petur Kradin, Richard L. Mark, Eugene J. TI Nodular Amiodarone Lung Disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE amiodarone; drug pneumonitis ID INDUCED PULMONARY TOXICITY; FINE-NEEDLE-ASPIRATION; LOW-DOSE AMIODARONE; MASS; PHOSPHOLIPIDOSIS; HEMORRHAGE; THERAPY AB The antiarrhythmic drug amiodarone accumulates in many organs of the body. Amiodarone lung disease (ALD) most commonly manifests clinically as all interstitial pneumonitis. The few reports of nodular ALD generally have been in the clinical and radiographic literature. No detailed histopathologic analysis of nodular ALD is available. We report 4 patients with nodular ALD. all of whom had excision of a nodule and none had a preoperative diagnosis of ALD. The radiographic suspicion before excisional biopsy in all 4 cases was malignancy. The initial pathologic suspicion in all 4 cases was either an abscess or vasculitis. In 3 of the 4 cases, where the dosages were known, each patient received 800mg/d for 7 or more months. All cases have strikingly similar histopathology, with vacuolated histiocytes massed within alveoli to form macroscopic modules with tissue breakdown. Ultrastructural examination Of lung and peripheral nerve in I case showed the characteristic inclusions of amiodarone in the cytoplasm of swollen histiocytes. Vacuolated histiocytes filled with these inclusions indicate the effect of the drug, but in these 4 cases there was tissue destruction, which indicated disease. The necrotizing nature of the massed histiocyles in the absence or infection or obstruction suggests the correct etiologic diagnosis even when the history of administration of the drug is not available at initial review. C1 [Ruangchira-Urai, Ruchira; Nielsen, G. Petur; Kradin, Richard L.; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Colby, Thomas V.] Mayo Clin, Dept Pathol, Scottsdale, AZ USA. [Ruangchira-Urai, Ruchira; Nielsen, G. Petur; Kradin, Richard L.; Mark, Eugene J.] Harvard Univ, Sch Med, Boston, MA USA. [Ruangchira-Urai, Ruchira] Siriraj Hosp Mahidol Univ, Dept Pathol, Bangkok, Thailand. [Klein, Julianne] St Boniface Gen Hosp, Dept Pathol, Winnipeg, MB R2H 2A6, Canada. RP Mark, EJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM emark@partners.org NR 34 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2008 VL 32 IS 11 BP 1654 EP 1660 DI 10.1097/PAS.0b013e31816d1cbc PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 369PB UT WOS:000260705300007 PM 18753942 ER PT J AU Ulbright, TM Young, RH AF Ulbright, Thomas M. Young, Robert H. TI Metastatic Carcinoma to the Testis A Clinicopathologic Analysis of 26 Nonincidental Cases With Emphasis on Deceptive Features SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testicular neoplasms; metastatic carcinoma; prostatic carcinoma; renal cell carcinoma; transitional cell carcinoma; colonic carcinoma; secondary neoplasms ID RENAL-CELL CARCINOMA; SECONDARY TESTICULAR-TUMORS; NEOPLASMS; LYMPHOMA; PROSTATE; EPIDIDYMIS; KRUKENBERG; CHILDREN; BLADDER; ADULTS AB Metastatic carcinomas to the testis may simulate primary testicular neoplasms, even in patients with known extratesticular primaries, but information on this topic is limited. We therefore reviewed our experience with 26 cases from consultation (N = 23) or hospital (N = 3) files, none of the cases were from autopsy material or incidentally discovered in therapeutic orchiectomies from patients with prostate cancer. The tumors occurred in men 29 to 90 years old, with the prostate the most common primary site (N = 11), followed by the renal parenchyma (N = 4), colon (N = 4), urinary tract (N = 3), lung (N = 2), esophagus (N = 1), and, most probably, small intestine (carcinoid, N = 1). Noteworthy findings included: the frequent absence of a known primary tumor (62%), the rarity of bilateral involvement (8%), the occasional lack of a distinct mass oil gross examination (15%), the infrequency Of multinodularity either grossly (8%) or microscopically (35%), the prominence of intertubular growth (42%), conspicuous intrarete or intratubular growth in some cases (especially prostate carcinoma) (19%), prominent cytoplasmic vacuoles in occasional cases (15%), and the frequent presence of lymphatic involvement (69%). Four tumors (3 prostate, 1 renal) with prominent intrarete and/or intratubular growth had submitting diagnoses of either a primary rete neoplasm or seminoma. Four tumors (2 prostate, 1 renal, and 1 bladder) with prominently vacuolated pale cells simulated Sertoli cell tumor. We conclude that, if autopsy cases and incidental tumors in therapeutic orchiectomy specimens are excluded, metastatic carcinomas to the testis are usually solitary, unilateral tumors that may simulate primary neoplasms, including rete adenocarcinoma and Sertoli cell tumor. Despite the rarity of documented cases in the literature, the bladder and renal pelvis should not be overlooked as possible sources for testicular metastasis. The pathologist must have a high index of suspicion for the possibility of a metastatic carcinoma to the testis for any testicular tumor where the routine light microscopic or immunohistochemical findings are unusual for a primary neoplasm. Clues to the likely primary site call usually be gleaned from the pathologic findings. C1 [Ulbright, Thomas M.] Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Ulbright, TM (reprint author), Clarian Pathol Lab, Room 4010,350 W 11th St, Indianapolis, IN 46202 USA. EM tulbrigh@iupui.edu NR 41 TC 35 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2008 VL 32 IS 11 BP 1683 EP 1693 DI 10.1097/PAS.0b013e3181788516 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 369PB UT WOS:000260705300011 PM 18769334 ER PT J AU Halla, YN O'Harea, AM Younga, BA Boyko, EJ Chertow, GM AF Halla, Y. N. O'Harea, A. M. Younga, B. A. Boyko, E. J. Chertow, G. M. TI Neighborhood poverty and kidney transplantation among US Asians and Pacific Islanders with end-stage renal disease SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Asian; end-stage renal disease; kidney transplant; Pacific Islander; poverty; racial disparities ID DISPARITIES GEOCODING PROJECT; RACIAL-DIFFERENCES; RESIDENTIAL SEGREGATION; HEALTH LITERACY; NATIONAL-SURVEY; UNITED-STATES; ACCESS; ORGANIZATION; MORTALITY; AMERICANS AB The degree to which low transplant rates among Asians and Pacific Islanders in the United States are confounded by poverty and reduced access to care is unknown. We examined the relationship between neighborhood poverty and kidney transplant rates among 22152 patients initiating dialysis during 1995-2003 within 1800 ZIP codes in California, Hawaii and the US-Pacific Islands. Asians and whites on dialysis were distributed across the spectrum of poverty, while Pacific Islanders were clustered in the poorest areas. Overall, worsening neighborhood poverty was associated with lower relative rates of transplant (adjusted HR [95% CI] for areas with >= 20% vs. < 5% residents living in poverty, 0.41 [0.32-0.53], p < 0.001). At every level of poverty, Asians and Pacific Islanders experienced lower transplant rates compared with whites. The degree of disparity increased with worsening neighborhood poverty (adjusted HR [95% CI] for Asians-Pacific Islanders vs. whites, 0.64 [0.51-0.80], p < 0.001 for areas with < 5% and 0.30 [0.21-0.44], p < 0.001 for areas with >= 20% residents living in poverty; race-poverty level interaction, p = 0.039). High levels of neighborhood poverty are associated with lower transplant rates among Asians and Pacific Islanders compared with whites. Our findings call for studies to identify cultural and local barriers to transplant among Asians and Pacific Islanders, particularly those residing in resource-poor neighborhoods. C1 [Halla, Y. N.; O'Harea, A. M.; Younga, B. A.; Boyko, E. J.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Halla, Y. N.; O'Harea, A. M.; Younga, B. A.; Boyko, E. J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Chertow, G. M.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. RP Halla, YN (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM ynhall@u.washington.edu FU Satellite Healthcare's Norman S. Coplon Extramural Grant Program; [K23 AG 028980-02]; [R01 DK079745-01]; [P30 DK 17407]; [R33 DK 067645-04]; [N01 DK 002498]; [U01 DK 066481-05] FX The authors are indebted to Su-Chun Cheng, DSc, MS, for her biostatistical guidance and support. Y.N.H. received support from Satellite Healthcare's Norman S. Coplon Extramural Grant Program. A. M.O. received support from K23 AG 028980-02. B.A.Y. received support from R01 DK079745-01. E.J.B. received support from P30 DK 17407. G. M. C. received support from R33 DK 067645-04, N01 DK 002498 and U01 DK 066481-05. The interpretation and reporting of the study data are the responsibility of the authors and NR 42 TC 30 Z9 30 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2008 VL 8 IS 11 BP 2402 EP 2409 DI 10.1111/j.1600-6143.2008.02413.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 358SE UT WOS:000259937000029 PM 18808403 ER PT J AU Harris, AM Chowdhury, F Begum, YA Khan, AI Faruque, ASG Svennerholm, AM Harris, JB Ryan, ET Cravioto, A Calderwood, SB Qadri, F AF Harris, Aaron M. Chowdhury, Fahima Begum, Yasmin Ara Khan, Ashraful Islam Faruque, Abu S. G. Svennerholm, Ann-Mari Harris, Jason B. Ryan, Edward T. Cravioto, Alejandro Calderwood, Stephen B. Qadri, Firdausi TI Shifting Prevalence of Major Diarrheal Pathogens in Patients Seeking Hospital Care during Floods in 1998, 2004, and 2007 in Dhaka, Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ENTEROTOXIGENIC ESCHERICHIA-COLI; COLONIZATION FACTORS; CHOLERA; ROTAVIRUS; EPIDEMICS; FEATURES; ETEC AB Bangladesh experienced severe flooding and diarrheal epidemics in 2007. We compared flood data from 2007 with 2004 and 1998 for diarrheal patients attending the ICDDR,B hospital in Dhaka. In 2007, Vibrio cholerae OI (33%), rotavirus (42%), and enterotoxigenic Escherichia coli (ETEC) (12%) were most prevalent. More severe dehydration was seen in 2007 compared with 2004 and 1998 (P < 0.001). In 2007, V. cholerae OI Inaba (52%) and Ogawa (48%) were seen, whereas in 2004 and 1998 it was primarily Inaba and the Ogawa types, respectively (P < 0.001). In 2007, 51% of ETEC produced the heat labile toxin (LT) (P < 0.001 compared with 2004), 22% expressed the heat stable (ST) (P < 0.001). and 27% were ST/LT positive (P = 0.231). The CS7 colonization factor (CF) was the most prevalent in 2007 (20% compared with 6% in 2004; P = 0.05). Our findings demonstrate alterations in clinical features and phenotypic changes of major bacterial pathogens in the recent Bangladesh flood. C1 Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. Univ Gothenburg, Inst Biomed, Dept Microbiol & Immunol, Sahlgrenska Acad, Gothenburg, Sweden. [Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02481 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Qadri, F (reprint author), ICDDRB, Div Sci Lab, Immunol Lab, 68 Shaheed Tajuddin Ahmed Sarani, Dhaka 1212, Bangladesh. EM aaron.harris@tufts.edu; fchowdhury@icddrb.org; yasmin@icddrb.org; ashrafk@icddrb.org; gfaruque@icddrb.org; ann-mari-Svennerholm@microbio.gu.se; jbharris@partners.org; etryan@partners.org; aeravioto@icddrb.org; scalderwood@partners.org; fqadri@mail.icddrb.org FU ICDDR,B [U01 AI058935, RO3 AI063079, R01 AI40725]; Swedish Agency for Research and Economic Cooperation [2004-0578]; Fogarty International Center at the National Institutes of Health [D43 TW005572] FX This research was supported by ICDDR,B and by the following grants: U01 AI058935 (S.B.C.): RO3 AI063079 (FQ); R01 AI40725 (E.T.R.): and the Swedish Agency for Research and Economic Cooperation (Sida-SAREC: Grant 2004-0578) (F.Q). Aaron Harris is recipient of the Fogarty/Ellison Fellowship in Global Health awarded by the Fogarty International Center at the National Institutes of Health (D43 TW005572). NR 26 TC 56 Z9 56 U1 0 U2 6 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2008 VL 79 IS 5 BP 708 EP 714 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 373BD UT WOS:000260945100016 PM 18981509 ER PT J AU Krane, SM AF Krane, Stephen M. TI The importance of proline residues in the structure, stability and susceptibility to proteolytic degradation of collagens SO AMINO ACIDS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Proline Metabolism in Health and Disease CY SEP 10-11, 2007 CL Frederick, MD DE prolylhydroxylases; collagen structure; osteogenesis imperfecta; collagenases; matrix metalloproteinases ID CARTILAGE-ASSOCIATED PROTEIN; MATRIX METALLOPROTEINASES; OSTEOGENESIS IMPERFECTA; I COLLAGEN; CLEAVAGE SITE; PROLYL 3-HYDROXYLATION; PARATHYROID-HORMONE; BINDING SITES; CDNA CLONING; TRIPLE-HELIX AB Collagens are among proteins that undergo several post-translational modifications, such as prolyl hydroxylation, that occur during elongation of the nascent chains in the endoplasmic reticulum. The major structural collagens, types I, II and III, have large, uninterrupted triple helices, comprising three polyproline II-like chains supercoiled around a common axis. The structure has a requirement for glycine, as every third residue, and is stabilized by the high content of proline and 4-hydroxyproline residues. Action of prolyl hydroxylases is critical. Spontaneous or targeted genetic defects in prolyl hydroxylases can be lethal or result in severe osteogenesis imperfecta. Prolines, as determinants of substrate specificity and susceptibility, also play a role in degradation of collagen by collagenolytic matrix metalloproteinases (MMPs). Targeted mutations in mice in the collagenase cleavage domain have profound effects on collagen turnover and the function of connective tissues. Prolines are thus critical determinants of collagen structure and function. C1 [Krane, Stephen M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. [Krane, Stephen M.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. RP Krane, SM (reprint author), Harvard Univ, Sch Med, Dept Med, Bldg 149,13th St,Room 8301, Boston, MA 02129 USA. EM krane.stephen@mgh.harvard.edu FU NIAMS NIH HHS [AR044815] NR 49 TC 50 Z9 50 U1 1 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 703 EP 710 DI 10.1007/s00726-008-0073-2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800008 PM 18431533 ER PT J AU Tambouret, RH AF Tambouret, Rosemary H. TI Diagnostic value of ProEX C in gynecological cytopathology SO ANNALES DE PATHOLOGIE LA French DT Article ID MINICHROMOSOME MAINTENANCE PROTEIN-2; SQUAMOUS INTRAEPITHELIAL LESIONS; TOPOISOMERASE-II-ALPHA; IMMUNOCYTOCHEMICAL ASSAY; CERVICAL CYTOLOGY; MIB-1 C1 Massachusetts Gen Hosp, Div Cytopathol, Boston, MA 02067 USA. RP Tambouret, RH (reprint author), Massachusetts Gen Hosp, Div Cytopathol, 55 Fruit St,Warren 2, Boston, MA 02067 USA. EM rtambouret@partners.org NR 7 TC 1 Z9 1 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0242-6498 J9 ANN PATHOL JI Ann. Pathol. PD NOV PY 2008 VL 28 BP S92 EP S93 DI 10.1016/j.annpat.2008.09.030 PG 2 WC Pathology SC Pathology GA 384ID UT WOS:000261737600029 PM 18984316 ER PT J AU Ay, H Arsava, EM Gungor, L Greer, D Singhal, AB Furie, KL Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, Ethem Murat Gungor, Levent Greer, David Singhal, Aneesh B. Furie, Karen L. Koroshetz, Walter J. Sorensen, A. Gregory TI Admission International Normalized Ratio and Acute Infarct Volume in Ischemic Stroke SO ANNALS OF NEUROLOGY LA English DT Article ID ATRIAL-FIBRILLATION; ENDOTHELIAL FUNCTION; ANTICOAGULATION; TRIAL; THROMBOLYSIS; ASSOCIATION; PREVENTION; REGRESSION; SEVERITY; THROMBUS AB Objective: The level of anticoagulation at the time of stroke onset may influence the size, composition, and dissolution rate of the occlusive clot. We explored the relation between admission international normalized ratio (INR) and acute infarct volume in patients with ischemic stroke. Methods: We studied 93 consecutive patients with preadmission warfarin use who had INR measurement and diffusion-weighted imaging performed within 24 hours of stroke onset. Ninety-three etiologic stroke subtype-matched patients without prior warfarin use served as control patients. Linear regression analysis was used to test for independence of INR as a predictor of infarct volume. Results: In patients with preadmission warfarin use, admission INR was inversely correlated with lesion volume oil diffusion-weighted imaging (r = -0-38). This relation was retained after adjustment for potential covariates (p = 0.014). INR less than 2.0 was associated with 3.5-fold (95% confidence interval, 2.9-4.2) greater lesion volume on diffusion-weighted imaging as compared with INR of 2.0 or more. Patients who were on therapeutic INR ( :2.0) had smaller infarcts compared with patients without preadmission warfarin use (p = 0.001). Admission INR was inversely correlated with acute perfusion defect (r = -0.33), chronic infarct volume (r = -0.42), National Institutes of Health Stroke Scale score at admission (r = -0.27), and modified Rankin score at discharge (r = -0.28). Interpretation: These results suggest that preadmission warfarin use associated with therapeutic level of anticoagulation can offer a benefit in limiting the extent of ischemic injury in an event of acute stroke. C1 [Ay, Hakan; Greer, David; Singhal, Aneesh B.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA USA. [Ay, Hakan; Arsava, Ethem Murat; Gungor, Levent; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol,Sch Med, Boston, MA USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Ay, H (reprint author), Harvard Univ, Sch Med, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013 OI Arsava, Ethem Murat/0000-0002-6527-4139 FU NIH (National Institute of Neurological Disorders and Stroke) [R01-NS038477, R01NS051412, P50-NS051343] FX This work was Supported by NIH (National Institute of Neurological Disorders and Stroke) grants R01-NS038477 (AGS), R01NS051412 (ABS) and P50-NS051343 (KLF). NR 27 TC 37 Z9 39 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2008 VL 64 IS 5 BP 499 EP 506 DI 10.1002/ana.21456 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 383BS UT WOS:000261649700009 PM 18661516 ER PT J AU Greenberg, SM Grabowski, T Gurol, ME Skehan, ME Nandigam, RNK Becker, JA Garcia-Alloza, M Prada, C Frosch, MP Rosand, J Viswanathan, A Smith, EE Johnson, KA AF Greenberg, Steven M. Grabowski, Thomas Gurol, M. Edip Skehan, Maureen E. Nandigam, R. N. Kaveer Becker, John A. Garcia-Alloza, Monica Prada, Claudia Frosch, Matthew P. Rosand, Jonathan Viswanathan, Anand Smith, Eric E. Johnson, Keith A. TI Detection of Isolated Cerebrovascular beta-Amyloid with Pittsburgh Compound B SO ANNALS OF NEUROLOGY LA English DT Article ID COGNITIVE IMPAIRMENT; CEREBRAL-HEMORRHAGE; ALZHEIMERS-DISEASE; ANGIOPATHY; BRAIN; DEPOSITION; MUTATION; PEPTIDE; MARKER; PIB AB Imaging of cerebrovascular beta-amyloid (cerebral amyloid angiopathy) is complicated by the nearly universal overlap of this pathology with Alzheimer's pathology. We performed positron emission tomographic imaging with Pittsburgh Compound B on 42-year-old man with early manifestations of Iowa-type hereditary cerebral amyloid angiopathy, a form of the disorder with little or no plaque deposits of fibrillar P-amyloid. The results demonstrated increased Pittsburgh Compound B retention selectively in occipital cortex, sparing regions typically labeled in Alzheimer's disease. These results offer compelling evidence that Pittsburgh Compound B positron emission tomography can noninvasively detect isolated cerebral amyloid angiopathy before overt signs of tissue damage such as hemorrhage or white matter lesions. C1 [Greenberg, Steven M.; Skehan, Maureen E.; Nandigam, R. N. Kaveer; Garcia-Alloza, Monica; Prada, Claudia; Rosand, Jonathan; Viswanathan, Anand; Smith, Eric E.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Grabowski, Thomas; Gurol, M. Edip] Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA 52242 USA. [Grabowski, Thomas] Univ Iowa, Coll Med, Dept Radiol, Iowa City, IA 52242 USA. [Becker, John A.; Johnson, Keith A.] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Smith, Eric/C-5443-2012; Gurol, Edip/J-2279-2014 OI Smith, Eric/0000-0003-3956-1668; Gurol, Edip/0000-0002-2169-4457 FU NIH [R01 AG026484]; Alzheimer's Association [IIRG-06-26331] FX This work was supported by the NIH (NIA) (R01 AG026484 S.M.G.) and the Alzheimer's Association (IIRG-06-26331 S.M.G.). NR 22 TC 46 Z9 46 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2008 VL 64 IS 5 BP 587 EP 591 DI 10.1002/ana.21528 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 383BS UT WOS:000261649700019 PM 19067370 ER PT J AU Pestalozzi, BC Francis, P Quinaux, E Dolci, S Azambuja, E Gelber, RD Viale, G Balil, A Andersson, M Nordenskjold, B Gnant, M Gutierrez, J Lang, I Crown, JPA Piccart-Gebhart, M AF Pestalozzi, B. C. Francis, P. Quinaux, E. Dolci, S. Azambuja, E. Gelber, R. D. Viale, G. Balil, A. Andersson, M. Nordenskjoeld, B. Gnant, M. Gutierrez, J. Lang, I. Crown, J. P. A. Piccart-Gebhart, M. CA Big 02-98 Collaborative Grp TI Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup phase III BIG 02-98 trial SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant chemotherapy; breast cancer; central nervous system; meningeal carcinomatosis; taxane; trastuzumab ID TRASTUZUMAB-BASED THERAPY; METASTASES; CHEMOTHERAPY; CARCINOMA; DOCETAXEL; WOMEN AB Background: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. Patients and methods: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG 02-98 trial comparing anthracycline-based adjuvant chemotherapy (control arms) to anthracycline-docetaxel-based sequential or concurrent chemotherapy (experimental arms). After a median follow-up of 5 years, 403 patients had died and detailed information on CNS relapse was collected for these patients. Results: CNS relapse occurred in 4.0% of control patients and 3.7% of docetaxel-treated patients. CNS relapse occurred in 27% of deceased patients in both treatment groups. CNS relapse was usually accompanied by neurologic symptoms (90%), and 25% of patients with CNS relapse died without evidence of extra-CNS relapse. Only 20% of patients survived 1 year from the diagnosis of CNS relapse. Prognosis of CNS relapse was worse for patients with meningeal carcinomatosis when compared with brain metastases. Unexpected findings included a higher rate of positive cerebrospinal fluid cytology (8% versus 3%) and more frequent use of magnetic resonance imaging for diagnosis (47% versus 30%) in the docetaxel-treated patients. Conclusion: There is no evidence that adjuvant docetaxel treatment is associated with an increased frequency of CNS relapse. C1 [Pestalozzi, B. C.] Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. [Francis, P.] Peter MacCallum Canc Ctr, Div Haematol & Med Oncol, Melbourne, Vic, Australia. [Francis, P.] Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Dolci, S.; Azambuja, E.] Inst Jules Bordet, Dept Oncol, B-1000 Brussels, Belgium. [Gelber, R. D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat Sci, Boston, MA 02115 USA. [Viale, G.] Univ Milan, Milan, Italy. [Viale, G.] European Inst Oncol, Dept Pathol, Milan, Italy. [Balil, A.] Hosp Univ Arnau Vilanova, Dept Oncol, Vilanova I La Geltru, Spain. [Andersson, M.] Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. [Nordenskjoeld, B.] Linkoping Univ Hosp, Dept Oncol, S-58185 Linkoping, Sweden. [Gnant, M.] Vienna Med Univ, Dept Surg 1, Vienna, Austria. [Gutierrez, J.] Clin Las Condes, Dept Haematol & Oncol, Santiago, Chile. [Lang, I.] Natl Inst Oncol, Dept Med Oncol, Budapest, Hungary. [Crown, J. P. A.] St Vincents Hosp, Dept Oncol, Dublin 4, Ireland. [Piccart-Gebhart, M.] Inst Jules Bordet, Coordinat Off, Breast Int Grp, Dept Med, B-1000 Brussels, Belgium. RP Pestalozzi, BC (reprint author), Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. EM bernhard.pestalozzi@usz.ch RI Francis, Prudence/J-4003-2012; OI Gnant, Michael/0000-0003-1002-2118 FU National Health and Medical Research Council [100925, 351164]; U. S. NCI [CA-73362]; Swiss Group for Clinical Cancer Research FX Australian New Zealand Breast Cancer Trials Group from National Health and Medical Research Council (100925 and 351164); U. S. NCI (CA-73362) to RDG; Swiss Group for Clinical Cancer Research. NR 13 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2008 VL 19 IS 11 BP 1837 EP 1841 DI 10.1093/annonc/mdn385 PG 5 WC Oncology SC Oncology GA 365BO UT WOS:000260381100003 PM 18562328 ER PT J AU Belperio, PS Mole, LA Halloran, J Boothroyd, DB Thomas, IC Backus, LI AF Belperio, Pamela S. Mole, Larry A. Halloran, James Boothroyd, Derek B. Thomas, I-Chun Backus, Lisa I. TI Postmarketing Use of Enfuvirtide in Veterans: Provider Compliance with Criteria for Use, Overall Efficacy, and Tolerability SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE compliance; enfuvirtide; HIV; outcome ID HIV-INFECTED PATIENTS; TREATMENT-EXPERIENCED PATIENTS; FUSION INHIBITOR ENFUVIRTIDE; PROTEASE INHIBITORS; RITONAVIR; TRIALS; SAFETY; T-20; THERAPY; WEEK-48 AB BACKGROUND: Most enfuvirtide outcomes data come from controlled trials of limited duration rather than from routine experience. Because of its uniqueness, the Veterans Health Administration (VHA) implemented specific enfuvirtide prescribing and follow-up criteria (criteria for use; CFU) and then assessed providers' compliance with these criteria and outcomes. OBJECTIVE: To report routine medical care experience with the prescribing, efficacy, and tolerability of enfuvirtide in a nonselective group of treatment-experienced, older, HIV-infected veterans. METHODS: Veterans receiving at least one outpatient prescription for enfuvirtide between April 2003 and July 2005 were identified from the VHA's HIV Clinical Case Registry (CCR:HIV). Targeted retrospective chart extraction was completed to address inclusion/exclusion criteria and to evaluate patients' continued use, adherence, and tolerance. CCR:HIV data were used for determination of demographics, prescription records, and laboratory results. The final cohort was used to assess providers' compliance with VHA's CFU for enfuvirtide. RESULTS: Of 275 evaluable subjects, between 52% and 93% who were prescribed enfuvirtide met each VHA CFU. Median change in CD4 cells and viral load from baseline to 6 months was +39 cells/mm(3) and -0.79 log(10) (p<0.001) and at 2 years was +72 cells/mm(3) and -1.57 log(10) (p<0.001); 41% and 55% of veterans achieved viral load less than 400 copies/mL at 6 months and 2 years, respectively. Seventy percent of veterans experienced injection site reactions (11 % were treatment-limiting). New or worsening adverse effects occurred in 56% of veterans: 32% gastrointestinal, 19% musculoskeletal, and 10% respiratory. Seventy percent of veterans discontinued enfuvirtide within 2 years; the largest portion (12%) stopped treatment within the first month. Documented reasons for discontinuation included patient request (42%), suboptimal response/progression (24%), toxicity (18%), death (13%), and transfer of care outside of the VHA (3%). CONCLUSIONS: In this treatment-experienced veteran cohort, providers prescribed enfuvirtide in accordance with most CFU, and favorable treatment responses were sustained in patients able to remain on therapy. Challenges that providers and patients face include ongoing education and support for successful long-term use. C1 [Mole, Larry A.; Halloran, James; Boothroyd, Derek B.; Thomas, I-Chun; Backus, Lisa I.] Ctr Qual Management Publ Hlth, Dept Vet Affairs, Palo Alto, CA USA. [Belperio, Pamela S.] Dept Vet Affairs, Los Angeles, CA USA. RP Belperio, PS (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM pamela.belperio@va.gov NR 19 TC 2 Z9 2 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2008 VL 42 IS 11 BP 1573 EP 1580 DI 10.1345/aph.1L265 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 369HG UT WOS:000260684600004 PM 18940919 ER PT J AU Wapnir, IL Aebi, S Gelber, S Anderson, SJ Lang, I Robidoux, A Mamounas, EP Wolmark, N AF Wapnir, Irene L. Aebi, Stefan Gelber, Shari Anderson, Stewart J. Lang, Istvan Robidoux, Andre Mamounas, Eleftherios P. Wolmark, Norman TI Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a Prospective Randomized Trial Evaluating Chemotherapy after Local Therapy for Isolated Locoregional Recurrences of Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID CONSERVATIVE SURGERY; RADIATION-THERAPY; TUMOR RECURRENCE; MULTIVARIATE-ANALYSIS; REGIONAL RECURRENCE; SALVAGE MASTECTOMY; PROGNOSIS; RELAPSE; UNIVARIATE; PATTERNS AB Background: The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab. Methods: The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients. Results: This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences. Conclusion: This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population. C1 [Wapnir, Irene L.; Anderson, Stewart J.; Mamounas, Eleftherios P.; Wolmark, Norman] Operat & Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project NSABP, Pittsburgh, PA USA. [Wapnir, Irene L.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Aebi, Stefan] Univ Hosp Bern, Dept Med Oncol, CH-3010 Bern, Switzerland. [Gelber, Shari] Int Breast Canc Study Grp IBCSG, Bern, Switzerland. [Gelber, Shari] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Stewart J.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Robidoux, Andre] Univ Montreal, Ctr Hosp, Montreal, PQ H3C 3J7, Canada. [Mamounas, Eleftherios P.] Aultman Canc Ctr, Canton, OH USA. [Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Wapnir, IL (reprint author), Operat & Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project NSABP, Pittsburgh, PA USA. EM wapnir@stanford.edu RI Aebi, Stefan/F-2004-2010; OI Aebi, Stefan/0000-0002-3383-9449; Anderson, Stewart/0000-0001-8948-0650 FU National Cancer Institute, Department of Health and Human Services [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651]; Swiss Group for Clinical Cancer Research (SAKK); Frontier Science and Technology Research Foundation; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; National Cancer Institute [CA-75362]; Swedish Cancer Society; Cancer Research Switzerland/Oncosuisse; Cancer Association of South Africa; Foundation for Clinical Research of Eastern Switzerland (OSKK) FX The authors would like to thank the participating centers, including the Dutch Breast Cancer Trialists' Group (BOOG), the Spanish Breast Cancer Research Group (GEICAM), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP). The authors would also like to thank Karen Price, Director of Scientific Administration for the International Breast Cancer Study Group (IBCSG). Supported in part by Public Health Service Grants U10CA-12027, U10CA-69974, U10CA-37377, and U10CA-69651 from the National Cancer Institute, Department of Health and Human Services. The International Breast Cancer Study Group is supported in part by the Swiss Group for Clinical Cancer Research (SAKK), the Frontier Science and Technology Research Foundation, the Cancer Council Australia, the Australian New Zealand Breast Cancer Trials Group, the National Cancer Institute (CA-75362), the Swedish Cancer Society, Cancer Research Switzerland/Oncosuisse, the Cancer Association of South Africa, and the Foundation for Clinical Research of Eastern Switzerland (OSKK). NR 25 TC 16 Z9 16 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 2008 VL 15 IS 11 BP 3227 EP 3231 DI 10.1245/s10434-008-0129-2 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 366UR UT WOS:000260509400033 PM 18784962 ER PT J AU Ford, RL Mains, IM Hilton, EJ Reeves, ST Stroud, RE Crawford, FA Ikonomidis, JS Spinale, FG AF Ford, Rachael L. Mains, Ira M. Hilton, Ebony J. Reeves, Scott T. Stroud, Robert E. Crawford, Fred A., Jr. Ikonomidis, John S. Spinale, Francis G. TI Endothelin-A Receptor Inhibition After Cardiopulmonary Bypass: Cytokines and Receptor Activation SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 07-10, 2007 CL Bonita Springs, FL SP SE Thorac Surg Assoc ID TUMOR-NECROSIS-FACTOR; PULMONARY ARTERIAL-HYPERTENSION; FACTOR-ALPHA GENE; CARDIAC-SURGERY; POSTOPERATIVE RECOVERY; INFLAMMATORY RESPONSE; SIGNAL-TRANSDUCTION; MESSENGER-RNA; ANTAGONIST; BOSENTAN AB Background. Basic studies have suggested that crosstalk exists between the endothelin-A receptor (ET-AR) and tumor necrosis factor signaling pathway. This study tested the hypothesis that administration of an ET-AR antagonist at the separation from cardiopulmonary bypass would alter the tumor necrosis factor activation in the early postoperative period. Methods. Patients (n = 44) were randomly allocated to receive bolus infusion of vehicle, 0.1, 0.5, 1, or 2 mg/kg of the ET-AR antagonist (sitaxsentan), at the separation from cardiopulmonary bypass (n = 9, 9, 9, 9, and 8, respectively). Plasma levels of tumor necrosis factor-alpha and soluble tumor necrosis factor receptor 1 and 2 were measured. Results. Compared with the vehicle group at 24 hours, plasma levels of tumor necrosis factor-alpha and tumor necrosis factor receptor 2 (indicative of receptor activation) were reduced in the 1 mg/kg ET-AR antagonist group (by approximately 13 pg/mL and approximately 0.5 ng/mL, respectively; p < 0.05). Plasma tumor necrosis factor receptor I levels also decreased (by approximately 1 ng/mL) after infusion of the higher doses of the ET-AR antagonist and remained lower (by approximately 3 ng/mL) at 24 hours after infusion (p < 0.05). In addition, a dose effect was observed between the ET-AR antagonist and these indices of tumor necrosis factor activation (p < 0.01). Conclusions. This study demonstrated a mechanistic relationship between the ET-AR and tumor necrosis factor receptor activation in the post-cardiac surgery period. Thus, in addition to the potential cardiovascular effects, a selective ET-AR antagonist can modify other biological processes relevant to the post-cardiac surgery setting. C1 [Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg & Anesthesia, Charleston, SC 29403 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg & Anesthesia, Strom Thurmond Res Bldg,114 Doughty St,Room 625, Charleston, SC 29403 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [R01 HL075488-04, HL075488, R01 HL057952, HL056603, HL057952, R01 HL056603, R01 HL056603-08, R01 HL057952-09, R01 HL075488] NR 38 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2008 VL 86 IS 5 BP 1576 EP 1583 DI 10.1016/j.athoracsur.2008.06.076 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 361RS UT WOS:000260145400026 PM 19049753 ER PT J AU Nilsson, O Allard, WJ Moore, RG Skates, SJ AF Nilsson, O. Allard, W. J. Moore, R. G. Skates, St. J. TI A BIOMARKER ALGORITHM OF HE4 AND CA125 FOR DIFFERENTIAL DIAGNOSIS IN WOMEN PRESENTING WITH ADNEXAL MASS SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Nilsson, O.; Allard, W. J.] Fjirebio Diagnost Inc, Malvern, PA USA. [Moore, R. G.] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Skates, St. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2008 VL 28 IS 6B MA 35 BP 4028 EP 4028 PG 1 WC Oncology SC Oncology GA 388WA UT WOS:000262049500064 ER PT J AU Hadlock, T Cheney, ML AF Hadlock, Tessa Cheney, Mack L. TI Facial Reanimation An Invited Review and Commentary SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Editorial Material ID GRACILIS MUSCLE TRANSPLANTATION; HERPES-SIMPLEX VIRUS; BELLS-PALSY; NERVE REGENERATION; MOTOR-NERVE; VIRAL-DNA; PARALYSIS; GRAFT; RECONSTRUCTION; PREDNISOLONE C1 [Hadlock, Tessa] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 44 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD NOV-DEC PY 2008 VL 10 IS 6 BP 413 EP 417 DI 10.1001/archfaci.10.6.413 PG 6 WC Surgery SC Surgery GA 395YE UT WOS:000262558600010 PM 19018064 ER PT J AU Kohen, R Cain, KC Mitchell, PH Becker, K Buzaitis, A Millard, SP Navaja, GP Teri, L Tirschwell, D Veith, R AF Kohen, Ruth Cain, Kevin C. Mitchell, Pamela H. Becker, Kyra Buzaitis, Ann Millard, Steven P. Navaja, Grace P. Teri, Linda Tirschwell, David Veith, Richard TI Association of Serotonin Transporter Gene Polymorphisms With Poststroke Depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDERS; PROMOTER POLYMORPHISM; SUICIDAL-BEHAVIOR; LIFETIME RISK; STROKE; METAANALYSIS; SYMPTOMS; 5-HTTLPR; REGION; PREDICTORS AB Context: Polymorphisms of the serotonin transporter gene (SERT) have been associated with mental illness. In people with long-term medical conditions, variants of the 5-HTTLPR and STin2 VNTR polymorphisms of SERT have been shown to confer a heightened vulnerability to comorbid depression. Objective: To determine whether the 5-HTTLPR, STin2 VNTR, and rs25531 polymorphisms of SERT are associated with poststroke depression (PSD) in stroke survivors. Design: A case-control study in which stroke survivors were screened for depressive symptoms and assigned to either a depressed group or a nondepressed group. Setting: Outpatient clinic. Participants: Seventy-five stroke survivors with PSD and 75 nondepressed stroke survivors. Interventions: Blood or saliva samples were collected from each participant for DNA extraction and genotyping. Main Outcome Measures: The associations between the 5-HTTLPR, STin2 VNTR, and rs25531 polymorphisms and PSD. Results: Individuals with the 5-HTTLPR s/s genotype had 3-fold higher odds of PSD compared with l/l or l/xl genotype carriers (odds ratio, 3.1; 95% confidence interval, 1.2-8.3). Participants with the STin2 9/12 or 12/12 genotype had 4-fold higher odds of PSD compared with STin2 10/10 genotype carriers (odds ratio, 4.1; 95% confidence interval, 1.2-13.6). An association of rs25531 with PSD was not shown. Conclusions: The 5-HTTLPR and the STin2 VNTR, but not the rs25531, polymorphisms of SERT are associated with PSD in stroke survivors. This gives further evidence of a role of SERT polymorphisms in mediating resilience to biopsychosocial stress. C1 [Kohen, Ruth; Navaja, Grace P.; Veith, Richard] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cain, Kevin C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Mitchell, Pamela H.; Buzaitis, Ann] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Becker, Kyra; Tirschwell, David] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Teri, Linda] Univ Washington, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. [Cain, Kevin C.] Univ Washington, Off Nursing Res, Seattle, WA 98195 USA. [Kohen, Ruth; Millard, Steven P.; Navaja, Grace P.] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kohen, R (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM ruko@u.washington.edu FU NIA NIH HHS [P50 AG005136, P50 AG005136-25]; NINR NIH HHS [R01 NR007755, R01 NR007755-04S2, R01NR007755] NR 43 TC 53 Z9 57 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2008 VL 65 IS 11 BP 1296 EP 1302 DI 10.1001/archpsyc.65.11.1296 PG 7 WC Psychiatry SC Psychiatry GA 368DA UT WOS:000260600300007 PM 18981341 ER PT J AU Olawaiye, AB Morgan, JA Goodman, A Fuller, AF Penson, RT AF Olawaiye, Alexander B. Morgan, JeVrey A. Goodman, AnneKathryn Fuller, Arlan F., Jr. Penson, Richard T. TI Epithelioid angiosarcoma of the uterus: a review of management SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Review DE epithelioid angiosarcoma; bevacizumab; Abraxane ID CUTANEOUS ANGIOSARCOMA; DOCETAXEL AB Background Uterine epithelioid angiosarcoma is extremely rare. Evidence-based advice regarding optimal management is lacking. Method We report the 22nd case in the world literature and review all the cases reported in English since 1900. An attempt is made to generate information that may help in the management based on the available literature. Results A 54-year-old woman was found to have an enlarged uterus on routine clinical examination. Although, she had no other symptoms, an endometrial biopsy was performed, which indicated a high-grade sarcoma. She was taken for a total abdominal hysterectomy and bilateral salpingo-oophorectomy and final histology returned a diagnosis of epithelioid angiosarcoma of the uterus. Two months later, she had tumor recurrence and was started on gemcitabine and taxotere later changed to albumin-bound paclitaxel (ABI-007, Abraxane (TM)) and bevacizumab. She was still alive with no evidence of disease at the time of this report, 12 months after diagnosis. Literature review suggests that surgical resection followed by chemotherapy is a reasonable management approach. Conclusion Uterine epithelioid angiosarcoma is an uncommon but very aggressive disease. Surgical resection followed by sequential chemotherapy is a reasonable management approach, and modern chemotherapy and anti-angiogenic agents may have merit. C1 [Penson, Richard T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol Oncol, Boston, MA 02114 USA. [Morgan, JeVrey A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fuller, Arlan F., Jr.] Winchester Hosp, Hematol & Oncol Ctr, Stoneham, MA 02180 USA. [Olawaiye, Alexander B.; Goodman, AnneKathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gynecol Oncol Div, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol Oncol, 55 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 15 TC 12 Z9 15 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0932-0067 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD NOV PY 2008 VL 278 IS 5 BP 401 EP 404 DI 10.1007/s00404-008-0727-z PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 346AI UT WOS:000259040400001 PM 18642010 ER PT J AU Bakshi, R Neema, M Healy, BC Liptak, Z Betensky, RA Buckle, GJ Gauthier, SA Stankiewicz, J Meier, D Egorova, S Arora, A Guss, ZD Glanz, B Khoury, SJ Guttmann, CRG Weiner, HL AF Bakshi, Rohit Neema, Mohit Healy, Brian C. Liptak, Zsuzsanna Betensky, Rebecca A. Buckle, Guy J. Gauthier, Susan A. Stankiewicz, James Meier, Dominik Egorova, Svetlana Arora, Ashish Guss, Zachary D. Glanz, Bonnie Khoury, Samia J. Guttmann, Charles R. G. Weiner, Howard L. TI Predicting Clinical Progression in Multiple Sclerosis With the Magnetic Resonance Disease Severity Scale SO ARCHIVES OF NEUROLOGY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the American-Academy-of-Neurology CY APR 28-MAY 05, 2007 CL Boston, MA SP Amer Acad Neurol ID BRAIN ATROPHY; WHITE-MATTER; MRI; DISABILITY; ABNORMALITIES; THERAPY; TRIAL; MS AB Background: Individual magnetic resonance imaging (MRI) disease severity measures, such as atrophy or lesions, show weak relationships to clinical status in patients with multiple sclerosis (MS). Objective: To combine MS-MRI measures of disease severity into a composite score. Design: Retrospective analysis of prospectively collected data. Setting: Community-based and referral subspecialty clinic in an academic hospital. Patients: A total of 103 patients with MS, with a mean (SD) Expanded Disability Status Scale (EDSS) score of 3.3 (2.2), of whom 62 (60.2%) had the relapsing-remitting, 33 (32.0%) the secondary progressive, and 8 (7.8%) the primary progressive form. Main Outcome Measures: Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV (T1: T2) assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1: T2. Results: The MRDSS score averaged 5.1 (SD, 2.6). Baseline MRI and EDSS correlations were moderate for BPF, T1: T2, and MRDSS and weak for T2LV. The MRDSS showed a larger effect size than the individual MRI components in distinguishing patients with the relapsing-remitting form from those with the secondary progressive form. Models containing either T2LV or MRDSS were significantly associated with disability progression during the mean (SD) 3.2 (0.3)-year observation period, when adjusting for baseline EDSS score. Conclusion: Combining brain MRI lesion and atrophy measures can predict MS clinical progression and provides the basis for developing an MRI-based continuous scale as a marker of MS disease severity. C1 [Bakshi, Rohit; Neema, Mohit; Healy, Brian C.; Buckle, Guy J.; Gauthier, Susan A.; Stankiewicz, James; Arora, Ashish; Guss, Zachary D.; Glanz, Bonnie; Khoury, Samia J.; Guttmann, Charles R. G.; Weiner, Howard L.] Harvard Univ, Sch Med, Partners MS Ctr, Brigham & Womens Hosp,Dept Neurol, Boston, MA 02115 USA. [Bakshi, Rohit; Liptak, Zsuzsanna; Meier, Dominik; Egorova, Svetlana; Guttmann, Charles R. G.] Harvard Univ, Sch Med, Partners MS Ctr, Brigham & Womens Hosp,Dept Radiol, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Bakshi, R (reprint author), Harvard Univ, Sch Med, Partners MS Ctr, Brigham & Womens Hosp,Dept Neurol, 77 Ave Louis Pasteur,Ste HIM 730, Boston, MA 02115 USA. EM rbakshi@bwh.harvard.edu OI khoury, samia/0000-0003-3198-6063 FU NINDS NIH HHS [1R01NS055083-01, R01 NS055083, R01 NS055083-01A1] NR 26 TC 27 Z9 27 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2008 VL 65 IS 11 BP 1449 EP 1453 DI 10.1001/archneur.65.11.1449 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 370XU UT WOS:000260797200006 PM 19001162 ER PT J AU Ratai, E Kok, T Wiggins, C Wiggins, G Grant, E Gagoski, B O'Neill, G Adalsteinsson, E Eichler, F AF Ratai, Eva Kok, Trina Wiggins, Christopher Wiggins, Graham Grant, Ellen Gagoski, Borjan O'Neill, Gilmore Adalsteinsson, Elfar Eichler, Florian TI Seven-Tesla Proton Magnetic Resonance Spectroscopic Imaging in Adult X-Linked Adrenoleukodystrophy SO ARCHIVES OF NEUROLOGY LA English DT Article ID IN-VIVO; CHILDHOOD ADRENOLEUKODYSTROPHY; ONSET ADRENOLEUKODYSTROPHY; ALZHEIMERS-DISEASE; MR SPECTROSCOPY; BRAIN; ADRENOMYELONEUROPATHY; PROGRESSION AB Background: Adults with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging. Objective: To test the hypothesis that neurochemistry in normal-appearing brains differs in adult phenotypes of X-ALD and that neurochemical changes correlate with the severity of symptoms. Patients and Methods: Using a 7-Tesla scanner, we performed structural and proton magnetic resonance spectroscopic imaging in 13 adult patients with X-ALD: 4 patients with adult cerebral ALD, 5 patients with adreno-myeloneuropathy (AMN), and 4 female heterozygotes. Nine healthy controls were included. Results: Among adult X-ALD phenotypes, the myoinositol to creatine ratio was 46% higher and the choline to creatine ratio was 21% higher in normal-appearing white matter of those with adult cerebral ALD compared with those with AMN (P<.05). Both N-acetylaspartate to creatine (P=.03) and glutamate to creatine (P=.04) ratios were lower in AMN patients than in controls. There were no significant differences between patients with AMN and female heterozygotes. In the cortex, patients with adult cerebral ALD had lower N-acetylaspartate to creatine ratios compared with female heterozygotes and controls (P=.02). The global myo-inositol to creatine ratio demonstrated a significant association with Expanded Disability Status Scale score (Spearman rho=0.66, P=.04). Conclusions: Seven-Tesla proton magnetic resonance spectroscopic imaging reveals differences in the neurochemistry of adult cerebral ALD but cannot distinguish AMN patients from female heterozygotes. Myo-inositol to creatine ratio correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD. C1 [Ratai, Eva; Wiggins, Christopher; Wiggins, Graham; Grant, Ellen] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [O'Neill, Gilmore; Eichler, Florian] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Neurol, Charlestown, MA USA. [Ratai, Eva; Wiggins, Christopher; Wiggins, Graham; Grant, Ellen; O'Neill, Gilmore; Eichler, Florian] Harvard Univ, Sch Med, Boston, MA USA. [Kok, Trina; Gagoski, Borjan; Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar] MIT, Harvard Massachusetts Inst Technol Hlth Sci & Tec, Cambridge, MA 02139 USA. RP Eichler, F (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM feichler@partners.org RI Adalsteinsson, Elfar/F-2477-2010 FU National Institutes of Health [R21NS059331, K08NS52550, R01NS050041, P41RR014075]; Robert J. Shillman Career Development Professorship FX This study was supported by grants R21NS059331, K08NS52550, R01NS050041, and P41RR014075 from the National Institutes of Health and by the Robert J. Shillman Career Development Professorship (Dr Adalsteinsson). NR 26 TC 12 Z9 12 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2008 VL 65 IS 11 BP 1488 EP 1494 DI 10.1001/archneur.65.11.1488 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 370XU UT WOS:000260797200013 PM 19001168 ER PT J AU Behlau, I Gilmore, MS AF Behlau, Irmgard Gilmore, Michael S. TI Microbial Biofilms in Ophthalmology and Infectious Disease SO ARCHIVES OF OPHTHALMOLOGY LA English DT Review ID PSEUDOMONAS-AERUGINOSA BIOFILMS; PHASE SIGMA-FACTOR; POLYSACCHARIDE INTERCELLULAR ADHESIN/HEMAGGLUTININ; EXPERIMENTAL BACTERIAL-ENDOCARDITIS; CATHETER-ASSOCIATED INFECTION; FOREIGN-BODY INFECTION; STAPHYLOCOCCUS-EPIDERMIDIS; CYSTIC-FIBROSIS; CRYSTALLINE KERATOPATHY; GENE-EXPRESSION AB Most bacterial infections involve biofilms. Biofilms are collections of microorganisms encased in a matrix that is often composed of both bacterial and host materials. They form on natural surfaces such as heart valves or abiotic surfaces such as contact lenses or intraocular lenses. The biofilm matrix promotes adherence of the microbe to smooth surfaces as well as to other cells. Biofilms thereby form large 3-dimensional microbial communities of complex architecture through cell-to-cell communication and coordinated multicellular behavior. The biofilm architecture promotes the exchange of nutrients and waste products. The ability of microorganisms to attach to abiotic surfaces and grow in highly stable communities greatly confounds the medical use of implantable devices. Much effort is now being invested to understand the molecular nature of biofilms, with a view toward designing biofilm-resistant implantable devices and more effective antimicrobials. C1 [Gilmore, Michael S.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gilmore, MS (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM michael.gilmore@schepens.harvard.edu FU National Institutes of Health [EY017381, EY08289] FX Portions of this study were supported by grants EY017381 and EY08289 from the National Institutes of Health. NR 156 TC 43 Z9 47 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2008 VL 126 IS 11 BP 1572 EP 1581 DI 10.1001/archopht.126.11.1572 PG 10 WC Ophthalmology SC Ophthalmology GA 370XV UT WOS:000260797300014 PM 19001227 ER PT J AU Reh, DD Metson, R Sindwani, R AF Reh, Douglas D. Metson, Ralph Sindwani, Raj TI Sinus Surgery in Patients With Previously Repaired Cerebrospinal Fluid Leaks SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CLINICAL-OUTCOMES; MANAGEMENT; COMPLICATIONS; RHINORRHEA AB Objective: To explore surgical technique and outcomes of revision endoscopic sinus surgery (ESS) in patients with previously repaired cerebrospinal fluid (CSF) leaks. Design: A case series of 13 patients with previously repaired iatrogenic CSF leaks who underwent revision ESS for recurrent sinus disease; a review of the preoperative workup, intraoperative findings, and postoperative outcomes. Setting: Two academic medical centers. Patients: Patients were included if they had a history of previously repaired skull base defect and iatrogenic CSF leak in the vicinity of the planned revision ESS. Interventions: Revision ESS was performed in the vicinity of the previously repaired CSF leak. Dissection was carefully performed to avoid a recurrent CSF leak. Main Outcome Measures: Preoperative workup, intraoperative findings, surgical technique, and complications were reviewed. Results: The study population consisted of 7 men and 6 women. Surgical navigation was used for all cases. Intrathecal fluorescein was not used in any case. In no instances was an active preexisting CSF leak identified or a new leak created. No minor or major postoperative complications arose in any of the study patients. All patients were discharged home within 24 hours. The mean (SD) follow-up was 26.0 (16.7) months. Conclusions: Previous skull base injury with CSF leak is not a contraindication to revision ESS. Safe ESS in this setting can be performed and may be recommended to such patients with symptomatic recurrence of their sinus disease. C1 [Sindwani, Raj] St Louis Univ Hosp, Dept Otolaryngol, St Louis, MO 63110 USA. [Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Reh, Douglas D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Sindwani, R (reprint author), St Louis Univ Hosp, Dept Otolaryngol, 3635 Vista Ave,6 FDT, St Louis, MO 63110 USA. EM Sindwani@slu.edu NR 13 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2008 VL 134 IS 11 BP 1187 EP 1190 DI 10.1001/archotol.134.11.1187 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 384IY UT WOS:000261739700010 PM 19015449 ER PT J AU Ogawa, F Mino-Kenudson, M Shimizu, M Ligato, S Lauwers, GY AF Ogawa, Fumihiro Mino-Kenudson, Mari Shimizu, Michio Ligato, Saverio Lauwers, Gregory Y. TI Gastroduodenitis Associated With Yttrium 90-Microsphere Selective Internal Radiation An Iatrogenic Complication in Need of Recognition SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID COLORECTAL LIVER METASTASES; Y-90 MICROSPHERES; HEPATIC METASTASES; THERAPY SIRT; CANCER; CHEMOTHERAPY; TUMORS; SIR-SPHERES(R); EXPERIENCE AB Context.-Selective internal radiation (SIR) therapy (SIRT) with yttrium 90 microspheres is increasingly used as an alternative therapeutic modality for patients with inoperable liver tumors. During administration of microspheres via the hepatic artery branches, some may on occasion be misdirected and be caught in the capillary bed of the duodenal and/or stomach. Objective.-To better characterize the histopathologic features of these complications. Design.-We report herein our experience with 3 patients who received SIR and developed gastroduodenal complications. Results.-SIR-microsphere-induced gastroduodenitis was diagnosed from 10 days to 5 months after treatment. In all 3 cases, purple particles measuring about 40 mu m in diameter were observed. An array of changes ranging from mucosal ulceration to epithelial changes were seen. Fibrinopurulent exudate was admixed with granulation tissue and reactive stromal cells. Epithelial changes included apoptosis and mucin depletion. Glandular cystic dilatation and epithelial flattening were also common as well as foveolar hyperplasia, suggestive of reparative changes in one case. Capillary ectasia and prominent plump endothelial cells were also present. Conclusion.-The spectrum of the alterations is consistent with radiotherapy-induced changes. Given the recent approval by the US Food and Drug Administration for the use of SIRT, it is anticipated that more patients will be treated with this modality. Pathologists should C1 [Ogawa, Fumihiro; Mino-Kenudson, Mari; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. [Shimizu, Michio] Saitama Med Sch, Dept Pathol, Saitama, Japan. [Ligato, Saverio] Hartford Hosp, Dept Pathol & Lab Med, Hartford, CT 06115 USA. [Ogawa, Fumihiro; Mino-Kenudson, Mari; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol WRN2, WRN2,55 Fruit St,Warren 2, Boston, MA 02114 USA. EM glauwers@partners.org NR 19 TC 18 Z9 18 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2008 VL 132 IS 11 BP 1734 EP 1738 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 369DV UT WOS:000260675400013 PM 18976008 ER PT J AU Etit, D Faquin, WC Gaz, R Randolph, G DeLellis, RA Pilch, BZ AF Etit, Demet Faquin, William C. Gaz, Randall Randolph, Gregory DeLellis, Ronald A. Pilch, Ben Z. TI Histopathologic and Clinical Features of Medullary Microcarcinoma and C-Cell Hyperplasia in Prophylactic Thyroidectomies for Medullary Carcinoma A Study of 42 Cases SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; RET PROTOONCOGENE MUTATIONS; THYROID-CARCINOMA; MALIGNANT PROGRESSION; CONSECUTIVE PATIENTS; SERUM CALCITONIN; CANCER; 2A; CHILDREN; SURVIVAL AB Context.-Prophylactic thyroidectomies are increasingly performed on patients at risk for developing medullary thyroid carcinoma (MTC); consequently, pathologists are more commonly encountering these specimens in routine practice. Objective.-To describe the detailed clinicopathologic features of prophylactic thyroidectomies for medullary carcinoma. Design.-We present a retrospective series of 42 prophylactic thyroidectomies for MTC performed for one or more of the following: family history of multiple endocrine neoplasia (MEN) or MTC, elevated serum calcitonin level, or detection of a RET proto-oncogene mutation. Results.-Patients included 22 men and 20 women (mean age, 26.2 years). Among those with known RET proto-oncogene mutations, affected sites included exons 10, 11, 14, and 16. In 93% (n = 39) of cases, either C-cell hyperplasia (n = 36), medullary microcarcinoma (MMC; n = 29), or medullary macrocarcinoma (n = 1) was found. C-cell hyperplasia was often multifocal (n = 30) and bilateral (n = 23) and included both nonnodular and nodular patterns. A total of 94% of C-cell hyperplasia cases and all MMC cases were microscopically detectable using hematoxylin-eosin stains. The MMCs were characterized by a complex microarchitectural pattern with a desmoplastic stromal response (n = 29) and focal amyloid deposition (n = 12). Most MMCs exhibited a solid pattern (n = 24) of round, polygonal, spindled, or plasmacytoid-shaped cells. Only 1 case of MMC showed evidence of metastatic disease to a pretracheal lymph node. Conclusions.-Based upon our clinicopathologic findings and review of the literature, we conclude that thyroidectomies in at-risk patients are very frequently associated with C-cell hyperplasia and/or MMC; however, the clinical prognosis for these patients is very good. C1 [Etit, Demet; Faquin, William C.; Pilch, Ben Z.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Gaz, Randall; Randolph, Gregory] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Faquin, William C.; Gaz, Randall; Randolph, Gregory; Pilch, Ben Z.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [DeLellis, Ronald A.] Brown Univ, Rhode Isl Hosp, Dept Pathol, Sch Med, Providence, RI 02903 USA. RP Pilch, BZ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02115 USA. EM bpilch@partners.org FU The Scientific and Technological Research Council of Turkey (TUBITAK) [B.02.1.TBT.0.06.01-219.01-880-5768] FX This study was partially supported by a grant (B.02.1.TBT.0.06.01-219.01-880-5768) from The Scientific and Technological Research Council of Turkey (TUBITAK). The authors thank Lisa Gallagher, MD, for her valuable support collecting multiple previous cases. NR 41 TC 26 Z9 27 U1 1 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2008 VL 132 IS 11 BP 1767 EP 1773 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 369DV UT WOS:000260675400018 PM 18976013 ER PT J AU Brose, SW Boninger, ML Fullerton, B McCann, T Collinger, JL Impink, BG Dyson-Hudson, TA AF Brose, Steven W. Boninger, Michael L. Fullerton, Bradley McCann, Thane Collinger, Jennifer L. Impink, Bradley G. Dyson-Hudson, Trevor A. TI Shoulder Ultrasound Abnormalities, Physical Examination Findings, and Pain in Manual Wheelchair Users With Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Rehabilitation; Shoulder; Spinal cord injuries; Ultrasonography; Wheelchairs ID ROTATOR CUFF TEARS; IMPINGEMENT SYNDROME; SUBACROMIAL BURSA; UPPER EXTREMITY; LABRAL TEARS; TENDON TEARS; INDEX WUSPI; DIAGNOSIS; ULTRASONOGRAPHY; INDIVIDUALS AB Objectives: To investigate the presence of ultrasound (US) abnormalities in manual wheelchair users with spinal cord injury (SCI) using a quantitative Ultrasound Shoulder Pathology Rating Scale (USPRS). To investigate physical examination (PE) findings using a quantitative Physical Examination of the Shoulder Scale (PESS), and to obtain data about pain and other subject characteristics such as age, years with SCI, and weight. Design: Case series. Setting: National Veterans' Wheelchair Games 2005 and 2006. Participants: Volunteer sample of manual wheelchair users with SCI participating in the National Veterans' Wheelchair Games. Interventions: Not applicable. Main Outcome Measures: Presence of relationships between US findings, PE findings, pain, and subject characteristics. Results: The USPRS correlated with age, duration of SCI, and weight (all P <.01), and showed a positive trend with the total Wheelchair User's Shoulder Pain Index (WUSPI) score (r=.258, P=.073). Several US findings related to presence of PE findings for specific structures. The PESS score correlated with the WUSPI (r=.679, P <.001) and duration of SCI (P <.05). The presence of untreated shoulder pain that curtailed activity was noted in 24.5% of subjects, and this was related to increased WUSPI scores (P=.002). Conclusions: PE and US abnormalities are common in manual wheelchair users with SCL The USPRS and PESS demonstrated evidence for external validity and hold promise as research tools. Untreated shoulder pain is common in manual wheelchair users with SCI, and further investigation of this pain is indicated. C1 [Brose, Steven W.; Boninger, Michael L.; Collinger, Jennifer L.] Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Boninger, Michael L.; Collinger, Jennifer L.; Impink, Bradley G.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Fullerton, Bradley] Patient Phys Partnership, Austin, TX USA. [Fullerton, Bradley] Childrens Hosp Austin, Austin, TX USA. [McCann, Thane] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA. [McCann, Thane] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Dyson-Hudson, Trevor A.] Kessler Med Rehabil Res & Educ Ctr, W Orange, NJ USA. [Dyson-Hudson, Trevor A.] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Sch Med, Newark, NJ 07103 USA. RP Brose, SW (reprint author), Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, 3471 5th Ave,Ste 201, Pittsburgh, PA 15213 USA. EM brosesw@upmc.edu OI Boninger, Michael/0000-0001-6966-919X FU Veterans Affairs Center of Excellence for Wheelchairs; Associated Rehabilitation [B3142C]; National Science Foundation [DGE0333420]; National Institute on Disability and Rehabilitation [H133N000019]; Paralyzed Veterans of America FX Supported by the Veterans Affairs Center of Excellence for Wheelchairs and Associated Rehabilitation (grant no. B3142C), the National Science Foundation (grant no. DGE0333420), the National Institute on Disability and Rehabilitation (grant no. H133N000019), and the Paralyzed Veterans of America. NR 44 TC 28 Z9 29 U1 1 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2008 VL 89 IS 11 BP 2086 EP 2093 DI 10.1016/j.apmr.2008.05.015 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 373PY UT WOS:000260985600006 PM 18996236 ER PT J AU Irani, JL Cutler, CS Whang, EE Clancy, TE Russell, S Swanson, RS Ashley, SW Zinner, MJ Raut, CP AF Irani, Jennifer L. Cutler, Corey S. Whang, Edward E. Clancy, Thomas E. Russell, Sara Swanson, Richard S. Ashley, Stanley W. Zinner, Michael J. Raut, Chandrajit P. TI Severe Acute Gastrointestinal Graft-vs-Host Disease An Emerging Surgical Dilemma in Contemporary Cancer Care SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the New-England-Surgical-Society CY SEP 15-17, 2006 CL Groton, CT SP New England Surg Soc ID BONE-MARROW-TRANSPLANTATION; PERIPHERAL-BLOOD; STEM-CELLS; SURGERY; ADULTS; MANAGEMENT; RECIPIENTS AB Objective: To determine the natural history of and guidelines for the surgical management of severe acute gastrointestinal (GI) graft-vs-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Design: Case series from a prospective database. Setting: Tertiary care referral center/National Cancer Institute-designated Comprehensive Cancer Center. Patients: A total of 63 of 2065 patients (3%) undergoing HSCT for hematologic malignancies from February 1997 to March 2005 diagnosed clinically with severe (stage 3 or 4) acute GI GVHD. Main Outcome Measure: Percutaneous or surgical intervention. Perforation, obstruction, ischemia, hemorrhage, and abscess were considered surgically correctable problems. Results: Severe acute GI GVHD was diagnosed in 63 patients (median age at HSCT, 47.6 years) at a median of 23 days after HSCT. Clinical diagnosis was confirmed histologically in 84% of patients. On computed tomography and/or magnetic resonance images, 64% had bowel wall thickening, 20% had a normal-appearing bowel, and 16% had nonspecific findings; none had evidence of perforation, obstruction, or abscess. All were initially treated with immunosuppression. Only 1 patient (1.6%) required intervention, undergoing a nontherapeutic laparotomy for worsening abdominal pain. A total of 83% of patients have died (median time to death from HSCT, 119 days; from GI GVHD diagnosis, 85 days). None who underwent an autopsy died of a surgically correctable cause. Conclusions: This series represents a large single-center experience with GI GVHD reviewed from a surgical perspective. Operative intervention was rarely required. Therefore, mature surgical judgment is necessary to confirm the absence of surgically reversible problems, thus avoiding unnecessary operations in this challenging patient population. C1 [Irani, Jennifer L.; Cutler, Corey S.; Whang, Edward E.; Clancy, Thomas E.; Russell, Sara; Swanson, Richard S.; Ashley, Stanley W.; Zinner, Michael J.; Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Surg, Boston, MA 02115 USA. [Cutler, Corey S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Raut, CP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 20 TC 9 Z9 11 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD NOV PY 2008 VL 143 IS 11 BP 1041 EP 1045 DI 10.1001/archsurg.143.11.1041 PG 5 WC Surgery SC Surgery GA 384JN UT WOS:000261741200002 PM 19015460 ER PT J AU Vagefi, PA Ferguson, CM Hall, JF AF Vagefi, Parsia A. Ferguson, Charles M. Hall, Jason F. TI Recurrent Gallstone Ileus Third Time Is the Charm SO ARCHIVES OF SURGERY LA English DT Article ID INTESTINAL-OBSTRUCTION C1 [Vagefi, Parsia A.; Ferguson, Charles M.; Hall, Jason F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Vagefi, PA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM pvagefi@partners.org NR 14 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD NOV PY 2008 VL 143 IS 11 BP 1118 EP 1120 DI 10.1001/archsurg.143.11.1118 PG 3 WC Surgery SC Surgery GA 384JN UT WOS:000261741200020 PM 19015472 ER PT J AU Coral-Ghanem, C Ghanem, VC Ghanem, RC AF Coral-Ghanem, Cleusa Ghanem, Vinicius Coral Ghanem, Ramon Coral TI Therapeutic contact lenses and the advantages of high Dk materials SO ARQUIVOS BRASILEIROS DE OFTALMOLOGIA LA Portuguese DT Article DE Contact lenses; hydrophilic; Hydrogels; Silicones; Epithelium; corneal/physiology; Wound healing/physiology; Keratitis; Photorefractive keratectomy; Visual acuity AB Therapeutic contact lenses are useful in a variety of ocular surface diseases. Their main indications are: to relieve the pain; protect ocular surface; promote corneal healing and epithelial regeneration; seal a leaking corneal wound and deliver ophthalmic drugs on the ocular surface. There are several kinds of lens designs and materials, and their choice is dependent on the specific disease to be treated, the duration of treatment and the physiologic needs of the diseased cornea. Bullous keratopathy, recurrent epithelial erosion syndrome, dry eye and postoperative epithelial defects are amongst their indications. Therapeutic contact lenses should not be indicated in the presence of active infectious keratitis or when the patient is not compliant. Corneal neovascularization, giant papillary conjunctivitis and infectious keratitis are serious complications, which can be prevented by correctly fitting and maintaining the therapeutic contact lenses. Silicon-hydrogel therapeutic contact lenses, due to their higher oxygen permeability, allow extended wear schedules, decreasing the need for frequent lens replacement. C1 [Coral-Ghanem, Cleusa] Univ Sao Paulo, USP, Fac Med, Area Concentracao Oftalmol, Sao Paulo, Brazil. [Coral-Ghanem, Cleusa] Hosp Olhos Sadalla Amin Ghanem, Dept Lentes Contato, Joinville, SC, Brazil. [Ghanem, Vinicius Coral] Univ Sao Paulo, USP, Sao Paulo, Brazil. [Ghanem, Vinicius Coral] Hosp Olhos Sadalla Amin Ghanem, Comissao Controle Infeccao Hosp, Joinville, SC, Brazil. [Ghanem, Vinicius Coral] Univ Estadual Campinas, UNICAMP, Campinas, SP, Brazil. [Ghanem, Vinicius Coral] Univ Calif Davis, EUA, Davis, CA 95616 USA. [Ghanem, Ramon Coral] Univ Sao Paulo, USP, Hosp Clin, Sao Paulo, Brazil. [Ghanem, Ramon Coral] Hosp Olhos Sadalla Amin Ghanem, Joinville, SC, Brazil. [Ghanem, Ramon Coral] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Coral-Ghanem, C (reprint author), Rua Abdon Batista 172, BR-89201010 Joinville, SC, Brazil. EM coral.joi@terra.com.br NR 12 TC 2 Z9 2 U1 1 U2 12 PU CONSEL BRASIL OFTALMOLOGIA PI SAO PAULO PA ALAMEDA SANTOS 1343, 11 ANDAR CJ 1110, CERQUEIRA CESAR, SAO PAULO, SP 00000, BRAZIL SN 0004-2749 J9 ARQ BRAS OFTALMOL JI Arq. Bras. Oftalmol. PD NOV-DEC PY 2008 VL 71 IS 6 SU S BP 19 EP 22 PG 4 WC Ophthalmology SC Ophthalmology GA V28GZ UT WOS:000208670600005 PM 19274406 ER PT J AU Joner, M Morimoto, K Kasukawa, H Steigerwald, K Merl, S Nakazawa, G John, MC Finn, AV Acampado, E Kolodgie, FD Gold, HK Virmani, R AF Joner, Michael Morimoto, Katsumi Kasukawa, Hiroaki Steigerwald, Kristin Merl, Sabine Nakazawa, Gaku John, Michael C. Finn, Aloke V. Acampado, Eduardo Kolodgie, Frank D. Gold, Herman K. Virmani, Renu TI Site-Specific Targeting of Nanoparticle Prednisolone Reduces In-Stent Restenosis in a Rabbit Model of Established Atheroma SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE stent; inflammation; steroids; atherosclerosis; restenosis ID DRUG-ELUTING STENTS; NEOINTIMAL HYPERPLASIA; CORONARY ANGIOPLASTY; CHONDROITIN SULFATE; CATIONIC LIPOSOMES; CELLS; HUMANS; GROWTH; CORTICOSTEROIDS; PREVENTION AB Objective-TRM-484 is a novel drug consisting of nanoparticles of prednisolone with high affinity to chondroitin sulfate proteoglycans (CSPGs). This may allow for neointimal suppression via directed targeting to areas of injury at systemic concentrations low enough to avoid adverse side effects known to occur with oral delivery of steroids. Methods and Results-Atherosclerotic New Zealand white Rabbits were implanted with bare metal stents and randomized to receive intravenous TRM-484 at doses of 1 mg/kg or 0.32 mg/kg starting at the day of stenting and continuing 3 times a week for the duration of the study. Control animals received empty liposomes (placebo) or saline infusion. Stented arterial segments were harvested at 42 days and processed for histomorphometry and immunohistochemistry. Tissue and plasma levels were determined along with confocal microscopic analysis to determine distribution of rhodamine-labeled TRM-484 at various time points. TRM-484 was exclusively observed at sites of stent-induced injury, with absence of drug in contralateral nonstented arteries. Tissue concentration of stented arteries exceeded that of contralateral nonstented arteries by 100-fold 24 hours after administration of 1 mg/kg TRM-484 and resulted in significant reduction of percent stenosis compared to saline and placebo treated rabbits (22.5 +/- 4.4 versus 31.0 +/- 8.4 and 29.5 +/- 8.1%, P < 0.03). Conclusion-TRM-484 at doses of 1 mg/kg resulted in significant suppression of in-stent neointimal growth in atherosclerotic rabbits. Site-specific targeting by this nanoparticle steroid in injured atherosclerotic areas might be a valuable and cost-effective approach for the prevention of in-stent restenosis. (Arterioscler Thromb Vasc Biol. 2008;28:1960-1966) C1 [Nakazawa, Gaku; Acampado, Eduardo; Kolodgie, Frank D.; Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD 20878 USA. [Steigerwald, Kristin; Merl, Sabine] Klinikum Rechts Der Isar, Deutsch Herzzentrum Muenchen, Munich, Germany. [Steigerwald, Kristin; Merl, Sabine] Klinikum Rechts Der Isar, Med Klin, Munich, Germany. [John, Michael C.; Finn, Aloke V.; Gold, Herman K.] Massachusetts Gen Hosp, Cardiac Unit, Dept Internal Med, Boston, MA 02114 USA. [Morimoto, Katsumi; Gold, Herman K.] Terumo Co Ltd, Ctr Res & Dev, Tokyo, Japan. RP Virmani, R (reprint author), CVPath Inst Inc, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org FU TERUMO corporation, Tokyo, Japan FX This study was in part sponsored by TERUMO corporation, Tokyo, Japan. NR 24 TC 50 Z9 54 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2008 VL 28 IS 11 BP 1960 EP U113 DI 10.1161/ATVBAHA.108.170662 PG 18 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 363NK UT WOS:000260273800014 PM 18688017 ER PT J AU Burkhardt, R Kenny, EE Lowe, JK Birkeland, A Josowitz, R Noel, M Salit, J Maller, JB Pe'er, I Daly, MJ Altshuler, D Stoffel, M Friedman, JM Breslow, JL AF Burkhardt, Ralph Kenny, Eimear E. Lowe, Jennifer K. Birkeland, Andrew Josowitz, Rebecca Noel, Martha Salit, Jacqueline Maller, Julian B. Pe'er, Itsik Daly, Mark J. Altshuler, David Stoffel, Markus Friedman, Jeffrey M. Breslow, Jan L. TI Common SNPs in HMGCR in Micronesians and Whites Associated With LDL-Cholesterol Levels Affect Alternative Splicing of Exon13 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE HMG-CoA reductase; SNP; genome-wide association study; LDL-C; alternative splicing ID GENOME-WIDE ASSOCIATION; COENZYME-A REDUCTASE; DENSITY-LIPOPROTEIN CHOLESTEROL; FEDERATED STATES; CANDIDATE GENES; RISK-FACTORS; DISEASE; LOCI; HYPERCHOLESTEROLEMIA; PATHOGENESIS AB Background-Variation in LDL-cholesterol (LDL-C) among individuals is a complex genetic trait involving multiple genes and gene-environment interactions. Methods and Results-In a genome-wide association study (GWAS) to identify genetic variants influencing LDL-C in an isolated population from Kosrae, we observed associations for SNPs in the gene encoding 3hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR). Three of these SNPs (rs7703051, rs12654264, and rs3846663) met the statistical threshold of genome-wide significance when combined with data from the Diabetes Genetics Initiative GWAS. We followed up the association results and identified a functional SNP in intron13 (rs3846662), which was in linkage disequilibrium with the SNPs of genome-wide significance and affected alternative splicing of HMGCR mRNA. In vitro studies in human lymphoblastoid cells demonstrated that homozygosity for the rs3846662 minor allele was associated with up to 2.2-fold lower expression of alternatively spliced HMGCR mRNA lacking exon13, and minigene transfection assays confirmed that allele status at rs3846662 directly modulated alternative splicing of HMGCR exon13 (42.9 +/- 3.9 versus 63.7 +/- 1.0%Delta exon13/total HMGCR mRNA, P = 0.02). Further, the alternative splice variant could not restore HMGCR activity when expressed in HMGCR deficient UT-2 cells. Conclusion-We identified variants in HMGCR that are associated with LDL-C across populations and affect alternative splicing of HMGCR exon13. (Arterioscler Thromb Vasc Biol. 2008; 28: 2078-2084) C1 [Breslow, Jan L.] Rockefeller Univ, Lab Biochem Genet, New York, NY 10065 USA. [Friedman, Jeffrey M.] Rockefeller Univ, Howard Hughes Med Inst, Mol Genet Lab, New York, NY 10065 USA. [Lowe, Jennifer K.; Maller, Julian B.; Daly, Mark J.; Altshuler, David] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Lowe, Jennifer K.; Maller, Julian B.; Daly, Mark J.; Altshuler, David] MIT, Cambridge, MA 02139 USA. [Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. [Maller, Julian B.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lowe, Jennifer K.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Daly, Mark J.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Stoffel, Markus] ETH, Inst Mol Syst Biol, Zurich, Switzerland. [Burkhardt, Ralph; Kenny, Eimear E.; Lowe, Jennifer K.; Birkeland, Andrew; Josowitz, Rebecca; Noel, Martha; Breslow, Jan L.] Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10065 USA. RP Breslow, JL (reprint author), Rockefeller Univ, Lab Biochem Genet, 1230 York Ave, New York, NY 10065 USA. EM breslow@rockefeller.edu RI Altshuler, David/A-4476-2009; Breslow, Jan/B-7544-2008; Burkhardt, Ralph/F-5221-2013; OI Altshuler, David/0000-0002-7250-4107; Maller, Julian/0000-0002-1565-9559; Burkhardt, Ralph/0000-0003-1924-1202 FU Deutsche Forschungsgemeinschaft [DFG Bu2263/1-1] FX Ralph Burkhardt is a fellow of the Deutsche Forschungsgemeinschaft (DFG Bu2263/1-1). NR 33 TC 78 Z9 78 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2008 VL 28 IS 11 BP 2078 EP U332 DI 10.1161/ATVBAHA.108.172288 PG 18 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 363NK UT WOS:000260273800031 PM 18802019 ER PT J AU Kozora, E Hanly, JG Lapteva, L Filley, CM AF Kozora, Elizabeth Hanly, John G. Lapteva, Larissa Filley, Christopher M. TI Cognitive Dysfunction in Systemic Lupus Erythematosus Past, Present, and Future SO ARTHRITIS AND RHEUMATISM LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; MAGNETIC-RESONANCE-SPECTROSCOPY; CEREBRAL-BLOOD-FLOW; GLUTAMATE-RECEPTOR ANTIBODIES; POSITRON-EMISSION-TOMOGRAPHY; CORTICOTROPIN-RELEASING-FACTOR; FAMILY-BASED ASSOCIATION; P-PROTEIN ANTIBODIES; KINASE M-ZETA; NEUROPSYCHIATRIC LUPUS C1 [Kozora, Elizabeth] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. [Kozora, Elizabeth; Filley, Christopher M.] Univ Colorado, Denver Sch Med, Boulder, CO 80309 USA. [Kozora, Elizabeth] Hosp Special Surg, New York, NY 10021 USA. [Hanly, John G.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Hanly, John G.] Dalhousie Univ, Halifax, NS, Canada. [Lapteva, Larissa] US FDA, Bethesda, MD 20014 USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Med & Res Ctr, 1400 Jackson St,B106, Denver, CO 80206 USA. EM kozorae@njc.org NR 186 TC 40 Z9 41 U1 3 U2 5 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 NOV PY 2008 VL 58 IS 11 BP 3286 EP 3298 DI 10.1002/art.23991 PG 13 WC Rheumatology SC Rheumatology GA 374JO UT WOS:000261039800003 PM 18975345 ER PT J AU Codolo, G Amedei, A Steere, AC Papinutto, E Cappon, A Polenghi, A Benagiano, M Paccani, SR Sambri, V Del Prete, G Baldari, CT Zanotti, G Montecucco, C D'Elios, MM de Bernard, M AF Codolo, Gaia Amedei, Amedeo Steere, Allen C. Papinutto, Elena Cappon, Andrea Polenghi, Alessandra Benagiano, Marisa Paccani, Silvia Rossi Sambri, Vittorio Del Prete, Gianfranco Baldari, Cosima Tatiana Zanotti, Giuseppe Montecucco, Cesare D'Elios, Mario Milco de Bernard, Marina TI Borrelia burgdorferi NapA-Driven Th17 Cell Inflammation in Lyme Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NEUTROPHIL-ACTIVATING PROTEIN; NECROSIS-FACTOR-ALPHA; HELICOBACTER-PYLORI; T-CELLS; HP-NAP; DESTRUCTIVE ARTHRITIS; RHEUMATOID-ARTHRITIS; POTENT STIMULATOR; IMMUNE-RESPONSES; SYNOVIAL-FLUIDS AB Objective. Human Lyme arthritis caused by Borrelia burgdorferi is characterized by an inflammatory infiltrate that consists mainly of neutrophils and T cells. This study was undertaken to evaluate the role of the innate and acquired immune responses elicited by the neutrophil-activating protein A (NapA) of B burgdorferi in patients with Lyme arthritis. Methods. Serum anti-NapA antibodies were measured in 27 patients with Lyme arthritis and 30 healthy control subjects. The cytokine profile of synovial fluid T cells specific for NapA was investigated in 5 patients with Lyme arthritis. The cytokine profile induced by NapA in neutrophils and monocytes was also investigated. Results. Serum anti-NapA antibodies were found in 48% of the patients with Lyme arthritis but were undetectable in the healthy controls. T cells from the synovial fluid of patients with Lyme arthritis produced interleukin-17 (IL-17) in response to NapA. Moreover, NapA was able to induce the expression of IL-23 in neutrophils and monocytes, as well as the expression of IL-6, IL-1 beta, and transforming growth factor beta (TGF beta) in monocytes, via Toll-like receptor 2. Conclusion. These findings indicate that NapA of B burgdorferi is able to drive the expression of IL-6, IL-1 beta, IL-23, and TGF beta by cells of the innate immune system and to elicit a synovial fluid Th17 cell response that might play a crucial role in the pathogenesis of Lyme arthritis. C1 [D'Elios, Mario Milco] Univ Florence, Dept Internal Med, I-50134 Florence, Italy. [Codolo, Gaia; Papinutto, Elena; Cappon, Andrea; Polenghi, Alessandra; Zanotti, Giuseppe; de Bernard, Marina] Univ Padua, Venetian Inst Mol Med, Padua, Italy. [Steere, Allen C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Steere, Allen C.] Harvard Univ, Sch Med, Boston, MA USA. [Papinutto, Elena] CNR, Ist Chim Biomol, Padua Sect, Padua, Italy. [Paccani, Silvia Rossi; Baldari, Cosima Tatiana] Univ Siena, I-53100 Siena, Italy. [Sambri, Vittorio] Univ Bologna, Bologna, Italy. [D'Elios, Mario Milco] Univ Careggi, Azienda Osped, Florence, Italy. RP D'Elios, MM (reprint author), Univ Florence, Dept Internal Med, Viale Morgagni 85, I-50134 Florence, Italy. EM delios@unifi.it; marina.debernard@unipd.it RI Amedei, Amedeo/G-5378-2011; OI Amedei, Amedeo/0000-0002-6797-9343; SAMBRI, VITTORIO/0000-0002-5012-7355; Zanotti, Giuseppe/0000-0002-0945-6501 FU NIH [AR-20358]; Associazione Italiana per la Ricerca SUI Cancro; Servizi CGN; University of Bologna [RFO 2007]; Italian Ministry of University and Research [2005060371, 2006064313]; Istituto Superiore di Sanita [6AC/F10] FX Supported by the NIH (grant AR-20358), the Associazione Italiana per la Ricerca SUI Cancro (regional grant), and Servizi CGN. Dr. Sambri's work was supported by the University of Bologna (RFO 2007). Drs. Montecucco and de Bernard's work was supported by the Italian Ministry of University and Research, Prin projects (grants 2005060371 and 2006064313, respectively). Dr. D'Elios' work was supported by the Istituto Superiore di Sanita (grant 6AC/F10). NR 48 TC 62 Z9 64 U1 1 U2 4 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 NOV PY 2008 VL 58 IS 11 BP 3609 EP 3617 DI 10.1002/art.23972 PG 9 WC Rheumatology SC Rheumatology GA 374JO UT WOS:000261039800037 PM 18975343 ER PT J AU Ozbaydar, M Elhassan, B Diller, D Massimini, D Higgins, LD Warner, JJP AF Ozbaydar, Mehmet Elhassan, Bassem Diller, David Massimini, Daniel Higgins, Laurence D. Warner, Jon J. P. TI Results of Arthroscopic Capsulolabral Repair: Bankart Lesion Versus Anterior Labroligamentous Periosteal Sleeve Avulsion Lesion SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE Shoulder; Anterior instability; Arthroscopy; Bankart repair; Anterior labroligamentous periosteal sleeve avulsion lesion; Suture anchor ID MULTIPLE SUTURE TECHNIQUE; SHOULDER INSTABILITY; FOLLOW-UP; GLENOHUMERAL JOINT; DISLOCATION; LABRUM; RECONSTRUCTION; STABILIZATION; POSTERIOR; LIGAMENT AB Purpose: The purpose of this Study was to evaluate the results of arthroscopic capsulolabral repair for traumatic anterior shoulder instability and to compare the outcome in patients who have Bankart lesions versus those with anterior labroligamentous periosteal sleeve avulsion (ALPSA) lesions. Methods: This study included 99 patients (93 shoulders), 72 male and 17 female, with a mean age of 32 years. who underwent arthroscopic Bankart repair for traumatic, recurrent anterior shoulder instability, by use Of suture anchors. In 67 shoulders (72%) a discrete Bankart lesion was repaired, and in 26 shoulders (28%) ail ALPSA lesion was repaired. The 2 groups were analyzed with regard to the number of preoperative dislocations and number of postoperative recurrences. Results: At a mean follow-up of 47 months (range, 24 to 98 months), recurrence of instability was documented in 10 shoulders (10.7%). Of the shoulders. 5 had Bankart lesions (7.4%) and 5 had ALPSA lesions (19.2%) (P = .0501). The mean number of dislocations or subluxations before the index surgery was significantly higher in the ALPSA group (mean, 12.3 [range, 2 to 57]) than in the Bankart group (mean, 4.9 [range, 2 to 24]) (P < .05). However, there were no significant differences in the number of anchors used. incidence of minor glenoid erosion, or incidence of bony Bankart lesions between the groups (P > .05 for all). Conclusions: Patients with ALPSA lesions present with a higher number of recurrent dislocations than those with discrete Bankart lesions. In addition, the failure rate after arthroscopic capsulolabral repair is higher in the ALPSA group than in the Bankart group. Level of Evidence: Level IV, therapeutic case series. C1 [Ozbaydar, Mehmet; Diller, David; Massimini, Daniel; Higgins, Laurence D.; Warner, Jon J. P.] Harvard Univ, Shoulder Serv, Boston, MA 02115 USA. [Higgins, Laurence D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Sports Med & Shoulder Serv, Boston, MA USA. [Warner, Jon J. P.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Elhassan, Bassem] Mayo Clin, Rochester, MN USA. RP Warner, JJP (reprint author), Harvard Univ, Shoulder Serv, 55 Fruit St, Boston, MA 02115 USA. EM jwarner@partners.org RI Ozbaydar, Mehmet/D-7391-2016 NR 39 TC 42 Z9 43 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD NOV PY 2008 VL 24 IS 11 BP 1277 EP 1283 DI 10.1016/j.arthro.2008.01.017 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 377TE UT WOS:000261272700012 PM 18971059 ER PT J AU Hamirani, YS Pandey, S Rivera, JJ Ndumele, C Budoff, MJ Blumenthal, RS Nasir, K AF Hamirani, Yasmin S. Pandey, Shivda Rivera, Juan J. Ndumele, Chiadi Budoff, Matthew J. Blumenthal, Roger S. Nasir, Khurram TI Markers of inflammation and coronary artery calcification: A systematic review SO ATHEROSCLEROSIS LA English DT Review DE Subclinical atherosclerosis; Inflammatory markers; Coronary artery calcium ID C-REACTIVE-PROTEIN; BEAM COMPUTED-TOMOGRAPHY; PERIPHERAL VASCULAR-DISEASE; 1ST MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; HEART-DISEASE; SUBCLINICAL ATHEROSCLEROSIS; RISK-FACTORS; ASYMPTOMATIC SUBJECTS; PROGNOSTIC VALUE AB Objectives: The goal of this systematic review is to assess the cross-sectional relationship of inflammatory markers with the presence and extent of coronary artery calcium (CAC) to identify asymptomatic individuals with a higher risk of coronary heart disease (CHID). Background: Markers of subclinical inflammation and subclinical atherosclerosis have both been used to improve detection of individuals at high risk of developing cardiovascular disease. CAC has emerged as a surrogate maker for underlying coronary atherosclerosis, and has been shown to predict future CHID events. Although inflammation is intimately associated with atherosclerosis, and levels of inflammatory markers predict cardiovascular risk, the relationship Of subclinical inflammatory markers with the burden of coronary atherosclerosis is not clear. Methods: Medline and Pub Med databases were searched for all studies assessing the relationship of inflammatory markers with CAC published till July 2007. Results: We found 12 studies that met our criteria. CRP, fibrinogen, metallic metalloproteinase-9 (MMP-9), rnonocyte chemotactic protein 1 (MCP-1), resistin, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), IL-6, tumor necrosis factor alpha (TNF-alpha) and beta-fibroblast growth factor (bFGF) were used as inflammatory markers. There was a wide variation among Studies with regards to population size, inclusion criterias, age range and techniques. It was observed that in almost all studies the relationship between inflammatory markers and CAC was weak, and was mostly found upon univariate analysis in women. However, this association was lost after correction for obesity and BMI. The data on the relationship of inflammation and CAC with progression of atherosclerosis is scarce and did not show any predictive benefits for future CHID. Conclusion: Variable associations between CAC and inflammatory markers were identified. In most Studies where a positive relationship was found, this relationship disappeared after appropriate correction for the presence of traditional risk factors. Our data suggests that an approach in which inflammatory markers are used to further characterize risk in individuals with an established coronary artery disease burden is more warranted than using biomarkers as sole risk predictors of future CHID events. Large, well-planned comprehensive Studies are required to identify the combined role of measuring inflammatory markers in assessment of atherosclerotic disease. (C) 2008 Published by Elsevier Ireland Ltd. C1 [Nasir, Khurram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac PET CT MRI Program, Boston, MA 02114 USA. [Hamirani, Yasmin S.] St Agnes Hosp, Dept Internal Med, Baltimore, MD USA. [Pandey, Shivda; Ndumele, Chiadi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Rivera, Juan J.; Blumenthal, Roger S.] Johns Hopkins Univ, Ciccarone Ctr Prevent Cardiol, Baltimore, MD USA. [Budoff, Matthew J.] Harbor UCLA Los Angeles Biomed Res Inst, Torrance, CA USA. RP Nasir, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac PET CT MRI Program, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM knasir@partners.org NR 43 TC 78 Z9 81 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2008 VL 201 IS 1 BP 1 EP 7 DI 10.1016/j.atherosclerosis.2008.04.045 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377QN UT WOS:000261265800001 PM 18561934 ER PT J AU Weylandt, KH Nadolny, A Kahlke, L Kohnke, T Schmocker, C Wang, JD Lauwers, GY Glickman, JN Kang, JX AF Weylandt, Karsten H. Nadolny, Anja Kahlke, Lena Koehnke, Thomas Schmoecker, Christoph Wang, Jingdong Lauwers, Gregory Y. Glickman, Jonathan N. Kang, Jing X. TI Reduction of inflammation and chronic tissue damage by omega-3 fatty acids in fat-1 transgenic mice with pancreatitis SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Omega-3 fatty acid; Fat-1; Acute pancreatitis; Chronic pancreatitis ID SYSTEMIC-DISEASE SEQUELAE; ACUTE NECROTIZING PANCREATITIS; POLYUNSATURATED FATTY-ACIDS; STELLATE CELLS; RESOLVIN E1; LUNG INJURY; RATS; SUPPLEMENTATION; INHIBITION; FIBROSIS AB Pancreatitis is a severe debilitating disease with high morbidity and mortality. Treatment is mostly supportive, and until now there are no clinically useful strategies for anti-inflammatory therapy. Although omega-3 polyunsaturated fatty acids (n-3 PUFA) are known to have anti-inflammatory effects, the utility of these fatty acids in the alleviation of pancreatitis remained to be investigated. The aim of this study was to examine the effect of n-3 PUFA on both acute and chronic pancreatitis in a well-controlled experimental system. We used the fat-1 transgenic mouse model, characterized by endogenously increased tissue levels of n-3 PUFA, and their wild-type littermates to examine the effect of n-3 PUFA on both acute and chronic cerulein-induced pancreatitis. Disease activity and inflammatory status were assessed by both histology and molecular methods. In acute pancreatitis, fat-1 mice showed a trend towards decreased necrosis and significantly reduced levels of plasma IL-6 levels as well as reduced neutrophil infiltration in the lung. In chronic pancreatitis there was less pancreatic fibrosis and collagen content accompanied by decreased pancreatic stellate cell activation in the fat-1 animals with increased n-3 PUFA tissue levels as compared to wild-type littermates with high levels of omega-6 (n-6) PUFA in their tissues. Our data provide evidence for a reduction of systemic inflammation in acute pancreatitis and of tissue fibrosis in chronic pancreatitis by increasing the tissue content of omega-3 polyunsaturated fatty acids. These results suggest a beneficial potential for n-3 PUFA supplementation in acute and particularly chronic pancreatitis. (c) 2008 Elsevier B.V. All rights reserved. C1 [Weylandt, Karsten H.; Nadolny, Anja; Kahlke, Lena; Koehnke, Thomas; Wang, Jingdong; Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Weylandt, Karsten H.; Nadolny, Anja; Kahlke, Lena; Koehnke, Thomas; Schmoecker, Christoph] Charite Univ Med Berlin, Rudolf Virchow Hosp, Dept Gastroenterol, D-13353 Berlin, Germany. [Glickman, Jonathan N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM jxkang@partners.org FU American Cancer Society [RSG-03-140-01-CNE]; NIH [NIH R01 113605] FX This work was supported by grants from the Biomedical Exchange Program (to L.K.), from the American Cancer Society (RSG-03-140-01-CNE) and the NIH (NIH R01 113605) (both to J.XX) and from Charite Medical School Research Grants (to K.H.W.). We thank Dr. Van Westerloo in Amsterdam for his help with the planning of experimental procedures, Lisa Sun for the help with the gas chromatography and Candice Romany for the support with the stainings. NR 45 TC 42 Z9 43 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD NOV PY 2008 VL 1782 IS 11 BP 634 EP 641 DI 10.1016/j.bbadis.2008.08.011 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 377PP UT WOS:000261263400004 PM 18832028 ER PT J AU Gruber, G Marshansky, V AF Grueber, Gerhard Marshansky, Vladimir TI New insights into structure-function relationships between archeal ATP synthase (A(1)A(0)) and vacuolar type ATPase (V1V0) SO BIOESSAYS LA English DT Review ID YEAST V-ATPASE; METHANOSARCINA-MAZEI GO1; PROTON-TRANSLOCATING ATPASE; IN-VIVO DISSOCIATION; RENAL TUBULAR-ACIDOSIS; AMINO-TERMINAL DOMAIN; MANDUCA-SEXTA MIDGUT; H+-ATPASE; NUCLEOTIDE-BINDING; ELECTRON-MICROSCOPY AB Adenosine triphosphate, ATP, is the energy currency of living cells. While ATP synthases of archae and ATP synthases of pro- and eukaryotic organisms operate as energy producers by synthesizing ATP, the eukaryotic V-ATPase hydrolyzes ATP and thus functions as energy transducer. These enzymes share features like the hydrophilic catalytic- and the membrane-embedded ion-translocating sector, allowing them to operate as nano-motors and to transform the transmembrane electrochemical ion gradient into ATP or vice versa. Since archaea are rooted close to the origin of life, the A-ATP synthase is probably more similar in its composition and function to the "original" enzyme, invented by Nature billion years ago. On the contrary, the V-ATPases have acquired specific structural, functional and regulatory features during evolution. This review will summarize the current knowledge on the structure, mechanism and regulation of A-ATP synthases and V-ATPases. The importance of V-ATPase in pathophysiology of diseases will be discussed. BioEssays 30:1096-1109, 2008. (C) 2008 Wiley Periodicals, Inc. C1 [Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. [Marshansky, Vladimir] Massachusetts Gen Hosp, Simches Res Ctr, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. RP Gruber, G (reprint author), Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 637551, Singapore. EM ggrueber@ntu.edu.sg FU NIDDK NIH HHS [DK057521-08, DK038452] NR 96 TC 48 Z9 50 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD NOV-DEC PY 2008 VL 30 IS 11-12 BP 1096 EP 1109 DI 10.1002/bies.20827 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 372PF UT WOS:000260912800010 PM 18937357 ER PT J AU Klekota, J Roth, FP AF Klekota, Justin Roth, Frederick P. TI Chemical substructures that enrich for biological activity SO BIOINFORMATICS LA English DT Article ID PROTEIN COUPLED RECEPTORS; SMALL-MOLECULE INHIBITOR; PRIVILEGED STRUCTURES; COMBINATORIAL SYNTHESIS; DRUG DISCOVERY; IRON CHELATORS; CYCLIC-PEPTIDES; POTENT; OPTIMIZATION; LIBRARIES AB Motivation: Certain chemical substructures are present in many drugs. This has led to the claim of privileged substructures which are predisposed to bioactivity. Because bias in screening library construction could explain this phenomenon, the existence of privilege has been controversial. Results: Using diverse phenotypic assays, we defined bioactivity for multiple compound libraries. Many substructures were associated with bioactivity even after accounting for substructure prevalence in the library, thus validating the privileged substructure concept. Determinations of privilege were confirmed in independent assays and libraries. Our analysis also revealed underprivileged substructures and conditional privilegerules relating combinations of substructure to bioactivity. Most previously reported substructures have been flat aromatic ring systems. Although we validated such substructures, we also identified three-dimensional privileged substructures. Most privileged substructures display a wide variety of substituents suggesting an entropic mechanism of privilege. Compounds containing privileged substructures had a doubled rate of bioactivity, suggesting practical consequences for pharmaceutical discovery. C1 [Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Klekota, Justin] Harvard Univ, Sch Med, Grad Biophys Program, Boston, MA 02115 USA. [Klekota, Justin] Harvard Inst Chem & Cell Biol, Boston, MA 02115 USA. RP Roth, FP (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA. RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU National Institutes of Health [R01 HG0017115, R01 HG003224, U01 HL81341] FX Keck Foundation (to F. P. R.); National Institutes of Health (grants R01 HG0017115, R01 HG003224 and U01 HL81341 to F. P. R.). NR 56 TC 80 Z9 81 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2008 VL 24 IS 21 BP 2518 EP 2525 DI 10.1093/bioinformatics/btn479 PG 8 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 365BP UT WOS:000260381200015 PM 18784118 ER PT J AU Lee, SJ Astigarraga, CC Eapen, M Artz, AS Davies, SM Champlin, R Jagasia, M Kernan, NA Loberiza, FR Bevans, M Soiffer, RJ Joffe, S AF Lee, Stephanie J. Astigarraga, Claudia C. Eapen, Mary Artz, Andrew S. Davies, Stella M. Champlin, Richard Jagasia, Madan Kernan, Nancy A. Loberiza, Fausto R., Jr. Bevans, Margaret Soiffer, Robert J. Joffe, Steven TI Variation in Supportive Care Practices in Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Practice variation; Supportive care; Autologous stem cell transplantation; Allogeneic stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; RANDOMIZED CONTROLLED-TRIALS; URSODEOXYCHOLIC ACID; PROTECTIVE ISOLATION; INFORMED-CONSENT; CLINICAL-TRIALS; EUROPEAN-GROUP; ACUTE GVHD; BLOOD AB Hematopoietic cell transplantation is an elective procedure that results in prolonged immune suppression and high treatment-related morbidity and mortality. Transplant centers and physicians use a variety of prophylaxis and monitoring strategies to prevent or minimize complications. Little is known about the variability in these practices. We conducted an international Internet-based survey of 526 physicians to describe the spectrum of supportive care practices employed. Consistency in pretransplant cardiac (96%) and pulmonary (95%) screening, informed consent documentation (93%), and use of antifungal prophylaxis (92%) was observed. Greater heterogeneity was seen in use of myelogenous growth factors, empiric antibiotic therapy, protective isolation procedures, posttransplant monitoring, and environmental and social restrictions. Although some practice differences were associated with physician characteristics and transplant type, most practice variation remained unexplained. These results suggest a need for well-designed observational and interventional studies to provide data about which supportive care practices improve outcomes. For practices proved to be beneficial, publication of guidelines and incorporation of monitoring into quality improvement initiatives may help standardize practices. C1 [Lee, Stephanie J.; Astigarraga, Claudia C.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Artz, Andrew S.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Davies, Stella M.] Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH USA. [Champlin, Richard] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Jagasia, Madan] Vanderbilt Univ, Ctr Med, Div Hematol Oncol, Nashville, TN 37232 USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, Pediat Bone Marrow Transplantat Serv, New York, NY 10021 USA. [Loberiza, Fausto R., Jr.] Univ Nebraska, Dept Med, Omaha, NE 68182 USA. [Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA. EM sjlee@fhcrc.org OI Kernan, Nancy/0000-0003-1417-1823; Joffe, Steven/0000-0002-0667-7384 FU Intramural NIH HHS [Z99 CL999999]; NCI NIH HHS [U24 CA076518] NR 34 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2008 VL 14 IS 11 BP 1231 EP 1238 DI 10.1016/j.bbmt.2008.08.008 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 367DY UT WOS:000260533900005 PM 18940677 ER PT J AU Krishnamurti, L Kharbanda, S Biernacki, MA Zhang, W Baker, KS Wagner, JE Wu, CJ AF Krishnamurti, Lakshmanan Kharbanda, Sandhya Biernacki, Melinda A. Zhang, Wandi Baker, K. Scott Wagner, John E. Wu, Catherine J. TI Stable Long-Term Donor Engraftment following Reduced-Intensity Hematopoietic Cell Transplantation for Sickle Cell Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Marrow and stem cell transplantation; Clinical results in inherited disorders; Conditioning regimen; Allo transplantation; Nonmyeloablative; Red cells; anemia-clinical; Sickle cell anemia ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; TOTAL LYMPHOID IRRADIATION; KILLER T-CELLS; APLASTIC-ANEMIA; CHIMERISM; THALASSEMIA; BLOOD; FLUDARABINE; GLOBULIN AB Reduced-intensity conditioning (RIC) regimens have the potential to decrease toxicities related to hematopoietic stem cell transplantation (HCT) in patients with sickle cell disease (SCD) and thus make HCTa more acceptable therapeutic option for this group of patients. We report the results of 7 patients enrolled on a study to evaluate safety and efficacy of HCT using bone marrow from an HLA matched sibling donor following an RIC regimen for patients with high-risk SCD. The conditioning regimen consisted of busulfan, fludarabine, equine antithymocyte globulin, and total lymphoid irradiation with shielding of the liver, lungs, heart, and gonads on day 1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The regimen was well tolerated, and all patients had hematopoietic recovery. Six of 7 patients are stably engrafted off immunosuppression and without sickle cell-related symptoms at 2 to 8.5 years after HCT Consistent with the complete resolution of SCID related symptoms observed in the 6 engrafted patients, erythropoiesis of complete or predominantly donor origin was detected by red blood cell-specific chimerism assays, despite their having persistent mixed chimerism in the mononuclear and lymphoid compartments. These findings demonstrate the curative potential of allogeneic HCT after an RIC regimen in patients with SCD. C1 [Krishnamurti, Lakshmanan] Univ Pittsburgh, Childrens Hosp Pittsburgh, Div Hematol Oncol Bone Marrow Transplantat, Pittsburgh, PA 15213 USA. [Kharbanda, Sandhya] Univ Alabama, Birmingham, AL USA. [Biernacki, Melinda A.; Zhang, Wandi; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baker, K. Scott; Wagner, John E.] Univ Minnesota, Minneapolis, MN USA. RP Krishnamurti, L (reprint author), Univ Pittsburgh, Childrens Hosp Pittsburgh, Div Hematol Oncol Bone Marrow Transplantat, 3705 5th Ave, Pittsburgh, PA 15213 USA. EM krislx@chp.edu RI Krishnamurti, Lakshmanan/F-7637-2011 NR 50 TC 52 Z9 52 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2008 VL 14 IS 11 BP 1270 EP 1278 DI 10.1016/j.bbmt.2008.08.016 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 367DY UT WOS:000260533900010 PM 18940682 ER PT J AU Allen, D Herbert, DC McMahan, CA Rotrekl, V Sobol, RW Wilson, SH Walter, CA AF Allen, Diwi Herbert, Damon C. McMahan, C. Alex Rotrekl, Vladimir Sobol, Robert W. Wilson, Samuel H. Walter, Christi A. TI Mutagenesis Is Elevated in Male Germ Cells Obtained from DNA Polymerase-beta Heterozygous Mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE base excision repair; DNA repair; gamete biology; gametogenesis; lacl; mutagenesis; POLB; spermatogenesis; spermatogenic cells ID BASE EXCISION-REPAIR; LIGASE-III; NUCLEAR EXTRACTS; MAMMALIAN-CELLS; POLY(ADP-RIBOSE) POLYMERASE; MEIOTIC RECOMBINATION; SPERMATOGENIC CELLS; MUTATION FREQUENCY; BINDING ACTIVITY; TRANSGENIC MICE AB Gametes carry the DNA that will direct the development of the next generation. By compromising genetic integrity, DNA damage and mutagenesis threaten the ability of gametes to fulfill their biological function. DNA repair pathways function in germ cells and serve to ameliorate much DNA damage and prevent mutagenesis. High base excision repair (BER) activity is documented for spermatogenic cells. DNA polymerase-beta (POLB) is required for the short-patch BER pathway. Because mice homozygous null for the Polb gene die soon after birth, mice heterozygous for Polb were used to examine the extent to which POLB contributes to maintaining spermatogenic genomic integrity in vivo. POLB protein levels were reduced only in mixed spermatogenic cells. In vitro short-patch BER activity assays revealed that spermatogenic cell nuclear extracts obtained from Polb heterozygous mice had one third the BER activity of age-matched control mice. Polb heterozygosity had no effect on the BER activities of somatic tissues tested. The Polb heterozygous mouse line was crossed with the lacl transgenic Big Blue mouse line to assess mutant frequency. The spontaneous mutant frequency for mixed spermatogenic cells prepared from Polb heterozygous mice was 2-fold greater than that of wild-type controls, but no significant effect was found among the somatic tissues tested. These results demonstrate that normal POLB abundance is necessary for normal BER activity, which is critical in maintaining a low germline mutant frequency. Notably, spermatogenic cells respond differently than somatic cells to Polb haploinsufficiency. C1 [Allen, Diwi; Herbert, Damon C.; Rotrekl, Vladimir; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. [Sobol, Robert W.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Sobol, Robert W.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. [Wilson, Samuel H.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Walter, Christi A.] Audie Murphy Mem Vet Affairs Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Mail Code 7762, San Antonio, TX 78229 USA. EM walter@uthscsa.edu RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 FU Elsa U. Pardee Foundation [P20 CA103730]; National Institutes of Health [1 R01 AG24364-01, AG21163]; National Institute of Environmental Health Sciences FX Supported by grant P20 CA103730 from the Elsa U. Pardee Foundation and the National Institutes of Health to R.W.S. and by grants 1 R01 AG24364-01 and AG21163 from the National Institutes of Health to C.A.W. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. The contents are solely the responsibility of the authors and do not necessarily reflect the views of the funding agencies. NR 73 TC 15 Z9 17 U1 0 U2 8 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 2008 VL 79 IS 5 BP 824 EP 831 DI 10.1095/biolreprod.108.069104 PG 8 WC Reproductive Biology SC Reproductive Biology GA 364FJ UT WOS:000260321300005 PM 18650495 ER PT J AU Kong, W Vanderburg, CR Gunshin, H Rogers, JT Huang, XD AF Kong, Wei Vanderburg, Charles R. Gunshin, Hiromi Rogers, Jack T. Huang, Xudong TI A review of independent component analysis application to microarray gene expression data SO BIOTECHNIQUES LA English DT Review ID NONNEGATIVE MATRIX FACTORIZATION; GGM-BASED ICA; FEATURE-EXTRACTION; ALGORITHMS; SEPARATION; CANCER; CLASSIFICATION; DECOMPOSITION; SIGNALS; DESIGN AB Independent component analysis (ICA) methods have received growing attention as effective data-mining tools for microarray gene expression data. As a technique of higher-order statistical analysis, ICA is capable of extracting biologically relevant gene expression features from microarray data. Herein we have reviewed the latest applications and the extended algorithms of ICA in gene clustering, classification. The theoretical frameworks of ICA have been described to further illustrate its feature extraction function in microarray data analysis. C1 [Kong, Wei; Huang, Xudong] Brigham & Womens Hosp, Conjugate & Med Chem Lab, Dept Radiol, Biomed Informat & Cheminformat Grp, Boston, MA 02115 USA. [Kong, Wei; Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kong, Wei] Shanghai Maritime Univ, Informat Engn Coll, Shanghai, Peoples R China. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Dept Neurol, Harvard NeuroDiscovery Ctr, Charlestown, MA USA. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Dept Neurol, Adv Tissue Resource Ctr, Charlestown, MA USA. [Vanderburg, Charles R.] Harvard Univ, Sch Med, Charlestown, MA USA. [Gunshin, Hiromi] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Nutr, Amherst, MA 01003 USA. [Rogers, Jack T.; Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA USA. [Rogers, Jack T.; Huang, Xudong] Harvard Univ, Sch Med, Charlestown, MA USA. RP Huang, XD (reprint author), Brigham & Womens Hosp, Conjugate & Med Chem Lab, Dept Radiol, Biomed Informat & Cheminformat Grp, 75 Francis St, Boston, MA 02115 USA. EM xhuang3@partners.org FU Research Foundation of Shanghai Municipal Education Commission [06FZ012, 2008098]; BWH Radiology Department; NIA/NIH [5R2IAG028850]; Alzheimer's Association [IIRG-07-60397] FX This work was supported by the Research Foundation of Shanghai Municipal Education Commission (nos. 06FZ012 and 2008098) and the research funds of the BWH Radiology Department. It was partially supported by the NIA/NIH (grant no. 5R2IAG028850, to XH.) and the Alzheimer's Association (grant no. IIRG-07-60397, to XH.). We thank Ms. Kim Lawson at the BWH Radiology Department for her extremely helpful comments and editing of our manuscript. This paper is subject to the NIH Public Access Policy. NR 63 TC 32 Z9 34 U1 0 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 2008 VL 45 IS 5 BP 501 EP + DI 10.2144/000112950 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411GL UT WOS:000263637200003 PM 19007336 ER PT J AU Turley, RS Terris, MK Kane, CJ Aronson, WJ Presti, JC Amling, CL Freedland, SJ AF Turley, Ryan S. Terris, Martha K. Kane, Christopher J. Aronson, William J. Presti, Joseph C., Jr. Amling, Christopher L. Freedland, Stephen J. CA SEARCH Database Study Grp TI The association between prostate size and Gleason score upgrading depends on the number of biopsy cores obtained: results from the Shared Equal Access Regional Cancer Hospital Database SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; prostate weight; upgrading; biopsy cores; risk ID RADICAL RETROPUBIC PROSTATECTOMY; SEARCH DATABASE; NEEDLE-BIOPSY; RISK-FACTORS; VOLUME; SPECIMENS; GRADE; HYPERPLASIA; ACCURACY; PROGRESSION AB OBJECTIVE To test the hypothesis that the association between prostate size and risk of Gleason grade upgrading varies as a function of sampling. PATIENTS AND METHODS We examined the association between pathological prostate weight, prostate biopsy scheme and Gleason upgrading (Gleason >= 7 at radical prostatectomy, RP) among 646 men with biopsy Gleason 2-6 disease treated with RP between 1995 and 2007 within the Shared Equal Access Regional Cancer Hospital Database using logistic regression. In all, 204 and 442 men had a sextant (six or seven cores) or extended-core biopsy (eight or more cores), respectively. Analyses were adjusted for centre, age, surgery, preoperative prostate-specific antigen level, clinical stage, body mass index, race, and percentage of cores positive for cancer. RESULTS In all, 281 men (44%) were upgraded; a smaller prostate was positively associated with the risk of upgrading in men who had an extended-core biopsy (P < 0.001), but not among men who had a sextant biopsy (P = 0.22). The interaction between biopsy scheme and prostate size was significant (P interaction = 0.01). CONCLUSIONS These data support the hypothesis that the risk of upgrading is a function of two opposing contributions: (i) a more aggressive phenotype in smaller prostates and thus increased risk of upgrading; and (ii) more thorough sampling in smaller prostates and thus decreased risk of upgrading. When sampled more thoroughly, the phenotype association dominates and smaller prostates are linked with an increased risk of upgrading. In less thoroughly sampled prostates, these opposing factors nullify, resulting in no association between prostate size and risk of upgrading. These findings help to explain previously published disparate results of the importance of prostate size as a predictor of Gleason upgrading. C1 [Turley, Ryan S.; Freedland, Stephen J.] Duke Univ, Sch Med, Div Urol Surg, Duke Prostate Ctr, Durham, NC 27710 USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Vet Affairs Med Ctr, Augusta, GA 30912 USA. [Kane, Christopher J.] Univ Calif San Francisco, San Francisco Sch Med, Dept Urol, San Francisco, CA 94143 USA. [Kane, Christopher J.] Univ Calif San Francisco, Urol Sect, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Urol Sect, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Amling, Christopher L.] Univ Alabama, Div Urol, Birmingham, AL USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Urol Sect, Vet Affairs Med Ctr, Durham, NC 27710 USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Div Urol Surg, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU Department of Veterans Affairs, the Georgia Cancer Coalition (MKT),; NIH [R01CA100938, P50 CA92131-01A1]; Department of Defense Prostate Cancer Research Program; American Urological Association Foundation/Astellas Rising Star in Urology Award FX Source of funding: the Department of Veterans Affairs, the Georgia Cancer Coalition (MKT), NIH grant R01CA100938 (WJA), NIH P50 CA92131-01A1 (WJA), the Department of Defense Prostate Cancer Research Program (SJF), and the American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF). NR 29 TC 20 Z9 20 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD NOV PY 2008 VL 102 IS 9 BP 1074 EP 1079 DI 10.1111/j.1464-410X.2008.08015.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 358TL UT WOS:000259940300007 PM 18778348 ER PT J AU Mak, RH Zietman, AL Heney, NM Kaufman, DS Shipley, WU AF Mak, Raymond H. Zietman, Anthony L. Heney, Niall M. Kaufman, Donald S. Shipley, William U. TI Bladder preservation: optimizing radiotherapy and integrated treatment strategies SO BJU INTERNATIONAL LA English DT Article ID TRANSITIONAL-CELL-CARCINOMA; THERAPY-ONCOLOGY-GROUP; PHASE-II TRIAL; SELECTIVE ORGAN PRESERVATION; COMBINED-MODALITY TREATMENT; GEMCITABINE PLUS CISPLATIN; QUALITY-OF-LIFE; NEOADJUVANT CHEMOTHERAPY; RADICAL RADIOTHERAPY; RADIATION-THERAPY AB While radical cystectomy (RC) remains the standard of care for muscle-invasive transitional cell carcinoma of the bladder, a series of single-institution and cooperative-group trials with a long-term follow-up have shown that combined modality therapy for bladder preservation can provide selected patients with an excellent chance for long-term survival with an intact, functioning bladder. Strategies for preserving the bladder have developed over the past 20 years, with continued refinements in radiation therapy, chemotherapy and patient selection. The hallmarks of modern bladder-preserving therapy include: (i) careful patient selection; (ii) combined therapy with maximum transurethral resection of bladder tumour, radiation and concurrent chemotherapy; (iii) cystoscopic assessment of the response to therapy with prompt salvage cystectomy for nonresponders; (iv) careful follow-up with cystoscopic surveillance and prompt cystectomy for invasive recurrence. Contemporary bladder-preserving approaches in patients with clinically staged muscle-invasive bladder cancer can achieve complete response rates of 60-85%, 5-year survival rates of 50-60%, and survival rates with an intact bladder of 40-45%. Although there are no randomized studies comparing RC with combined therapies for bladder preservation, long-term data show that overall and disease-specific survival rates in contemporary RC series of clinically staged patients with T2-T4a bladder cancer are comparable to those of bladder-preserving protocols. Thus, combined modality therapy for bladder preservation has become a safe, tested and effective alternative to RC in selected patients with muscle-invasive bladder cancer who desire to keep their bladders. Future work will continue to refine the bladder-preserving approach to improve survival and local control. C1 [Zietman, Anthony L.; Shipley, William U.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Heney, Niall M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Kaufman, Donald S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Mak, Raymond H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Radiat Oncol Residency Program, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM WShipley@partners.org NR 64 TC 18 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD NOV PY 2008 VL 102 IS 9 BP 1345 EP 1353 DI 10.1111/j.1464-410X.2008.07981.x PN B PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 361HB UT WOS:000260117200023 PM 19035903 ER PT J AU Nanda, A D'Amico, AV AF Nanda, Akash D'Amico, Anthony V. TI Combined radiation and hormonal therapy or dose escalation for men with unfavourable-risk prostate cancer: an evidence-based approach using a synthesis of randomized clinical trials SO BJU INTERNATIONAL LA English DT Review ID ANDROGEN SUPPRESSION; RADIOTHERAPY; ADENOCARCINOMA C1 [Nanda, Akash; D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA. RP Nanda, A (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. EM ananda@partners.org NR 12 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD NOV PY 2008 VL 102 IS 10 BP 1366 EP 1368 DI 10.1111/j.1464-410X.2008.08027.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 364JZ UT WOS:000260333300003 PM 18778343 ER PT J AU Lichterfeld, M Mou, D Cung, TDH Williams, KL Waring, MT Huang, J Pereyra, F Trocha, A Freeman, GJ Rosenberg, ES Walker, BD Yu, XG AF Lichterfeld, Mathias Mou, Danlei Cung, Thai Duong Hong Williams, Katie L. Waring, Michael T. Huang, Jinghe Pereyra, Florencia Trocha, Alicja Freeman, Gordon J. Rosenberg, Eric S. Walker, Bruce D. Yu, Xu G. TI Telomerase activity of HIV-1-specific CD8(+) T cells: constitutive up-regulation in controllers and selective increase by blockade of PD ligand 1 in progressors SO BLOOD LA English DT Article ID LONG-TERM NONPROGRESSORS; HIV-1 INFECTION; VIRUS-REPLICATION; LIFE-SPAN; LENGTH; MEMORY; ACTIVATION; PROLIFERATION; EXPRESSION; DIFFERENTIATION AB Exhaustion of virus-specific T cells may play an important role in the pathophysiology of chronic viral infections. Here, we analyzed telomere length and telomerase activity in HIV-1-specific CD8(+) T cells from progressors or controllers to determine underlying molecular pathways of T-cell exhaustion and senescence. Telomere lengths of HIV-1-specific CD8(+) T cells from progressors were significantly shorter compared with autologous cytomegalovirus (CMV)/Epstein-Barr virus (EBV)-specific CD8(+) T cells or bulk CD8(+) T cells, while telomere lengths from controllers significantly exceeded those of autologous bulk CD8(+) T cells and reached a similar level as HIV-1-specific CD8(+) T cells collected during primary HIV-1 infection. Telomere length stabilization in controllers corresponded to high levels of constitutive telomerase activity, which was associated with preservation of cytotoxic and proliferative properties. Conversely, limited constitutive telomerase activity was observed in HIV-1 specific CD8(+) T cells from progressors, although an increase in both telomere length and telomerase activity was achieved in antigenic-peptide-stimulated cells from progressors after blocking the PD-1/PD ligand 1 (PD-L1) pathway. Collectively, these data suggest a causal role of telomere shortening for the functional deficiencies of HIV-1-specific CD8(+) T cells in chronic progressive infection, while high constitutive telomerase activities appears to contribute to maintenance of polyfunctional HIV-1-specific CD8(+) T cells from HIV-1 controllers. (Blood. 2008; 112: 3679-3687) C1 [Lichterfeld, Mathias; Mou, Danlei; Cung, Thai Duong Hong; Williams, Katie L.; Waring, Michael T.; Huang, Jinghe; Pereyra, Florencia; Trocha, Alicja; Rosenberg, Eric S.; Walker, Bruce D.; Yu, Xu G.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. [Lichterfeld, Mathias; Mou, Danlei; Cung, Thai Duong Hong; Williams, Katie L.; Waring, Michael T.; Huang, Jinghe; Pereyra, Florencia; Trocha, Alicja; Rosenberg, Eric S.; Walker, Bruce D.; Yu, Xu G.] Harvard Univ, Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02115 USA. [Lichterfeld, Mathias; Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. [Waring, Michael T.; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yu, XG (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. EM xyu@partners.org RI Huang, Jinghe/O-1986-2015 FU National Institutes of Health [AI068499, AI078799, AI56299]; Harvard University Research Enabling Grant; Doris Duke Clinical Scientist Development Award; Claflin Distinguished Scholar Award FX This study was supported by grants from the National Institutes of Health to X. G. Y. (AI068499, AI078799) and G. J. F. (AI56299). X. G. Y. is a recipient of a Harvard University Research Enabling Grant, the Doris Duke Clinical Scientist Development Award, and the Claflin Distinguished Scholar Award. NR 45 TC 46 Z9 49 U1 1 U2 7 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 NOV 1 PY 2008 VL 112 IS 9 BP 3679 EP 3687 DI 10.1182/blood-2008-01-135442 PG 9 WC Hematology SC Hematology GA 363XW UT WOS:000260301800027 PM 18728248 ER PT J AU Goss, PE AF Goss, Paul E. TI Letrozole in the extended adjuvant setting: MA.17 (vol 105, Suppl 1, pg 45, 2008) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Correction C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Cox Bldg,Room 640, Boston, MA 02114 USA. EM pgoss@partners.org NR 1 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2008 VL 112 IS 2 BP 369 EP 369 DI 10.1007/s10549-007-9849-4 PG 1 WC Oncology SC Oncology GA 360NO UT WOS:000260064400020 ER PT J AU Brown, JR Neuberg, D Phillips, K Reynolds, H Silverstein, J Clark, JC Ash, M Thompson, C Fisher, DC Jacobsen, E LaCasce, AS Freedman, AS AF Brown, Jennifer R. Neuberg, Donna Phillips, Kimberly Reynolds, Hazel Silverstein, Jason Clark, Jennifer C. Ash, Megan Thompson, Christina Fisher, David C. Jacobsen, Eric LaCasce, Ann S. Freedman, Arnold S. TI Prevalence of familial malignancy in a prospectively screened cohort of patients with lymphoproliferative disorders SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol DE familial lymphoma; familial chronic lymphocytic leukaemia; heritable; lifetime risk ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; INTERLYMPH-CONSORTIUM; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; GENETIC-VARIATION; CANCER INCIDENCE; DOWN-REGULATION; POOLED ANALYSIS; RISK AB Increasing evidence points to a heritable contribution in the development of lymphoma. The goal of this study was to determine the rate of familial lymphoproliferative malignancy among consecutive lymphoma patients presenting to a tertiary care center and to enrol families with multiple affected first-degree relatives on a data and tissue collection study. Beginning in 2004 all new patients presenting to the Dana-Farber Cancer Institute with non-Hodgkin (NHL) or Hodgkin lymphoma (HL) or chronic lymphocytic leukaemia (CLL) were asked to complete a one-page self-administered family history questionnaire. 55.4% of 1948 evaluable patients reported a first-degree relative with a malignancy, with the highest rate among CLL probands. Lymphoid malignancies were particularly common, with 9.4% of all probands reporting a first-degree relative with a related lymphoproliferative disorder (LPD). This frequency was again highest for CLL, at 13.3% of CLL probands, compared to 8.8% of NHL probands and 5.9% of HL probands (P = 0.002). The prevalence of CLL was significantly increased in parents of CLL probands (P < 0.05), and a greater risk of NHL was seen in fathers of NHL probands than in mothers (P = 0.026). We conclude that familial aggregation of LPDs is common among newly diagnosed patients, varies significantly by diagnosis and contributes meaningfully to the population disease burden. C1 [Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brown, Jennifer R.; Fisher, David C.; Jacobsen, Eric; LaCasce, Ann S.; Freedman, Arnold S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jbrown2@partners.org FU NCI NIH HHS [K23 CA115682-03, K23 CA115682, K23 CA115682-04, K23 CA115682-01, K23 CA115682-02, P01 CA092625, 2P01CA092625] NR 43 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2008 VL 143 IS 3 BP 361 EP 368 DI 10.1111/j.1365-2141.2008.07355.x PG 8 WC Hematology SC Hematology GA 361HC UT WOS:000260117300006 PM 18729853 ER PT J AU Lee, SJ Richardson, PG Sonneveld, P Schuster, MW Irwin, D Miguel, JFS Crawford, B Massaro, J Dhawan, R Gupta, S Anderson, KC AF Lee, Stephanie J. Richardson, Paul G. Sonneveld, Pieter Schuster, Michael W. Irwin, David Miguel, Jesus-F. San Crawford, Bruce Massaro, Joseph Dhawan, Ravinder Gupta, Sanjay Anderson, Kenneth C. TI Bortezomib is associated with better health-related quality of life than high-dose dexamethasone in patients with relapsed multiple myeloma: results from the APEX study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE bortezomib; dexamethasone; quality of life; multiple myeloma; randomised clinical trial ID STEM-CELL TRANSPLANTATION; REPORTED OUTCOMES; ONCOLOGY-GROUP; EUROPEAN-ORGANIZATION; RANDOMIZED-TRIAL; CLINICAL-TRIALS; DOUBLE-BLIND; CANCER; CHEMOTHERAPY; SURVIVAL AB Health-related quality of life (HRQL) was prospectively measured during the phase III APEX trial of bortezomib versus dexamethasone in relapsed multiple myeloma patients. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core (QLQ-C30) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (NTX) side-effects questionnaires were administered at baseline and every 6 weeks up to 42 weeks. Patients receiving bortezomib (1.3 mg/m(2), days 1, 4, 8 and 11 for eight 3-week cycles, then days 1, 8, 15 and 22 for three 5-week cycles; n = 296) demonstrated significantly better mean Global Health Status over the study versus patients receiving dexamethasone (40 mg/d, days 1-4, 9-12, and 17-20 for four 5-week cycles, then days 1-4 only for five 4-week cycles; n = 302), plus significantly better physical health, role, cognitive, and emotional functioning scores, lower dyspnoea and sleep symptom scores, and better NTX questionnaire score, using multiple imputation to account for missing data. Results were similar using available-data analyses. Sensitivity analyses suggested that improved HRQL with bortezomib is at least partially explained by improved survival. These results show that bortezomib was associated with significantly better multidimensional HRQL compared with dexamethasone, consistent with the better clinical outcomes seen with bortezomib. C1 [Lee, Stephanie J.; Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonneveld, Pieter] Univ Rotterdam Hosp, Rotterdam, Netherlands. [Schuster, Michael W.] New York Presbyterian Hosp, New York, NY USA. [Irwin, David] Alta Bates Canc Ctr, Berkeley, CA USA. [Miguel, Jesus-F. San] Hosp Univ Salamanca, Salamanca, Spain. [Crawford, Bruce] Mapi Values, Cambridge, MA USA. [Massaro, Joseph] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Dhawan, Ravinder] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Gupta, Sanjay] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D5-290,POB 19024, Seattle, WA 98109 USA. EM sjlee@fhcrc.org RI 2008, Ibsal/A-1268-2012; OI Massaro, Joseph/0000-0002-2682-4812; SAN MIGUEL, JESUS/0000-0002-9183-4857 NR 43 TC 33 Z9 35 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2008 VL 143 IS 4 BP 511 EP 519 DI 10.1111/j.1365-2141.2008.07378.x PG 9 WC Hematology SC Hematology GA 364JX UT WOS:000260333100007 PM 18986387 ER PT J AU Neri, P Tagliaferri, P Di Martino, MT Calimeri, T Amodio, N Bulotta, A Ventura, M Eramo, PO Viscomi, C Arbitrio, M Rossi, M Caraglia, M Munshi, NC Anderson, KC Tassone, P AF Neri, Paola Tagliaferri, Pierosandro Di Martino, Maria Teresa Calimeri, Teresa Amodio, Nicola Bulotta, Alessandra Ventura, Monica Eramo, Pasqua Orietta Viscomi, Caterina Arbitrio, Mariamena Rossi, Marco Caraglia, Michele Munshi, Nikhil C. Anderson, Kenneth C. Tassone, Pierfrancesco TI In vivo anti-myeloma activity and modulation of gene expression profile induced by valproic acid, a histone deacetylase inhibitor SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; valproic acid; histone deacetylase inhibitor; SCID mice; pathfinder analysis ID HUMAN MULTIPLE-MYELOMA; SUBEROYLANILIDE HYDROXAMIC ACID; CELL-CYCLE; PHASE-I; DEPSIPEPTIDE FR901228; CLINICAL DEVELOPMENT; CANCER-TREATMENT; DRUG-RESISTANCE; HDAC INHIBITORS; LEUKEMIA CELLS AB Valproic acid (VPA) is a well-tolerated anticonvulsant that exerts anti-tumour activity as a histone deacetylase inhibitor. This study investigated the in vitro and in vivo activity of VPA against multiple myeloma (MM) cells. In vitro exposure of interleukin-6-dependent or -independent MM cells to VPA inhibited cell proliferation in a time- and dose-dependent manner and induced apoptosis. In a cohort of severe combined immunodeficiency mice bearing human MM xenografts, VPA induced tumour growth inhibition and survival advantage in treated animals versus controls. Flow cytometric analysis performed on MM cells from excised tumours showed increase of G(0)-G(1) and a decreased G(2)/M- and S-phase following VPA treatment, indicating in vivo effects of VPA on cell cycle regulation. Gene expression profiling of MM cells exposed to VPA showed downregulation of genes involved in cell cycle progression, DNA replication and transcription, as well as upregulation of genes implicated in apoptosis and chemokine pathways. Pathfinder analysis of gene array data identified cell growth, cell cycle, cell death, as well as DNA replication and repair as the most important signalling networks modulated by VPA. Taken together, our data provide the preclinical rationale for VPA clinical evaluation as a single agent or in combination, to improve patient outcome in MM. C1 [Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Med Oncol Unit, I-88100 Catanzaro, Italy. [Neri, Paola; Tagliaferri, Pierosandro; Di Martino, Maria Teresa; Calimeri, Teresa; Amodio, Nicola; Bulotta, Alessandra; Ventura, Monica; Eramo, Pasqua Orietta; Viscomi, Caterina; Arbitrio, Mariamena; Rossi, Marco; Tassone, Pierfrancesco] Tommaso Campanella Canc Ctr, Catanzaro, Italy. [Neri, Paola; Munshi, Nikhil C.; Anderson, Kenneth C.; Tassone, Pierfrancesco] Dana Farber Canc Inst, Jerome Lipper Multiple Myelome Ctr, Boston, MA 02115 USA. [Neri, Paola; Munshi, Nikhil C.; Tassone, Pierfrancesco] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Arbitrio, Mariamena] Natl Res Council CNR ISN, Pharmacol Sect, Catanzaro, Italy. [Caraglia, Michele] Univ Naples 2, Sch Med, Dept Biochem & Biophys, Naples, Italy. RP Tassone, P (reprint author), Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Med Oncol Unit, Viale Europa, I-88100 Catanzaro, Italy. EM tassone@unicz.it RI Caraglia, Michele/N-5670-2015; Amodio, Nicola/K-7335-2016; OI Caraglia, Michele/0000-0003-2408-6091; Amodio, Nicola/0000-0002-1345-4410; ROSSI, Marco/0000-0002-7258-475X FU Associazione Italiana per la Ricerca sul Cancro NR 61 TC 42 Z9 43 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2008 VL 143 IS 4 BP 520 EP 531 DI 10.1111/j.1365-2141.2008.07387.x PG 12 WC Hematology SC Hematology GA 364JX UT WOS:000260333100008 PM 18986388 ER PT J AU Jagannath, S Barlogie, B Berenson, JR Siegel, DS Irwin, D Richardson, PG Niesvizky, R Alexanian, R Limentani, SA Alsina, M Esseltine, DL Anderson, KC AF Jagannath, Sundar Barlogie, Bart Berenson, James R. Siegel, David S. Irwin, David Richardson, Paul G. Niesvizky, Ruben Alexanian, Raymond Limentani, Steven A. Alsina, Melissa Esseltine, Dixie-Lee Anderson, Kenneth C. TI Updated survival analyses after prolonged follow-up of the phase 2, multicenter CREST study of bortezomib in relapsed or refractory multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE bortezomib; multiple myeloma; relapsed; refractory; survival ID THERAPY; SAFETY; TRIAL AB The Clinical Response and Efficacy Study of Bortezomib in the Treatment of Relapsing Multiple Myeloma (CREST) demonstrated substantial activity with two dose levels of bortezomib (1.0 and 1.3 mg/m(2)), alone or with dexamethasone, in relapsed or refractory multiple myeloma. We present updated survival analyses after prolonged follow-up (median > 5 years). One- and 5-year survival rates were 82% and 32%, respectively, in the 1.0 mg/m(2) group (n = 28), and 81% and 45%, respectively, in the 1.3 mg/m(2) group (n = 26). Notable survival, response, and time-to-progression data suggest that a bortezomib starting dose of 1.3 mg/m(2) is preferred. If bortezomib dose reduction is required, the 1.0 mg/m(2) dose still offers patients a substantial survival benefit. C1 [Jagannath, Sundar] St Vincents Comprehens Canc Ctr, New York, NY 10011 USA. [Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Berenson, James R.] Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. [Siegel, David S.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Irwin, David] Alta Bates Canc Ctr, Berkeley, CA USA. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Niesvizky, Ruben] Cornell Univ, New York Presbyterian Hosp, Weill Cornell Med Coll, Ithaca, NY 14853 USA. [Alexanian, Raymond] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Limentani, Steven A.] Carolina Hematol Oncol Associates, Charlotte, NC USA. [Alsina, Melissa] Univ S Florida, H Lee Moffitt Canc Ctr, Res Inst, Tampa, FL 33682 USA. [Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Jagannath, S (reprint author), St Vincents Comprehens Canc Ctr, 325 W 15th St Between 8th & 9th Ave, New York, NY 10011 USA. EM sjagannath@aptiumoncology.com FU Millennium Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development L. L.C. FX We thank Steve Hill, Sarah Maloney and Jane Saunders for their assistance in drafting this report. Steve Hill and Sarah Maloney are medical writers and Jane Saunders is a medical editor with Gardiner-Caldwell London. This research was supported by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development L. L.C. NR 12 TC 53 Z9 56 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2008 VL 143 IS 4 BP 537 EP 540 DI 10.1111/j.1365-2141.2008.07359.x PG 4 WC Hematology SC Hematology GA 364JX UT WOS:000260333100010 PM 18783399 ER PT J AU Hata, Y Sassa, Y Kita, T Miura, M Kano, K Kawahara, S Arita, R Nakao, S Shih, JL Ishibashi, T AF Hata, Y. Sassa, Y. Kita, T. Miura, M. Kano, K. Kawahara, S. Arita, R. Nakao, S. Shih, J. L. Ishibashi, T. TI Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DIABETIC-RETINOPATHY; CELLS; TRANSCRIPTION; ANGIOGENESIS; PATHWAY; STRETCH; EYE AB Aim: Tumour necrosis factor-alpha (TNF-alpha) is one of the major inflammatory cytokines involved in the pathogenesis of various vitreoretinal diseases. The authors investigated the effect of hypoxia, TNF-alpha and dexamethasone on vascular endothelial growth factor (VEGF) expression by cultured hyalocytes. Methods: Hyalocytes were isolated from bovine vitreous. Hypoxic and TNF-alpha-dependent effects on cultured hyalocytes were investigated using several assays to determine VEGF protein expression, hypoxia-inducible factor (HIF)-1 alpha protein levels, HIF-1 alpha-DNA-binding ability and VEGF mRNA stability. The effects of dexamethasone on VEGF expression and its intracellular signalling under hypoxic or TNF-alpha stimulated conditions were also examined. Results: Hypoxic conditions and TNF-alpha stimulation induce VEGF expression in hyalocytes. These stimuli also stabilise HIF-1 alpha protein and increase its DNA-binding ability. Dexamethasone significantly inhibits both HIF-1 alpha protein levels and HIF-1 alpha-DNA-binding activity, and also decreases the hypoxic-and TNF-alpha-dependent induction of VEGF expression in hyalocyte. However, dexamethasone has no significant effect on the stability of VEGF mRNA. Conclusions: Hyalocytes may be involved in various vitreoretinal diseases by increasing HIF-1 alpha protein stability and HIF-1 alpha-DNA binding, and thus increasing VEGF production under pathological conditions. Dexamethasone seems to be capable of inhibiting hypoxic and TNF-alpha dependent VEGF production, presumably via its inhibitory effects on HIF-1 alpha protein levels and its DNA-binding activity. C1 [Hata, Y.; Sassa, Y.; Kita, T.; Miura, M.; Kano, K.; Kawahara, S.; Arita, R.; Nakao, S.; Ishibashi, T.] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan. [Shih, J. L.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Hata, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM hatachan@med.kyushu-u.ac.jp RI Sassa, Yukio/H-6339-2012 FU Ministry of Education, Science, Sports and Culture, Japan [19592026] FX The study was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (Grant-in-Aid for Scientific Research #19592026). NR 21 TC 12 Z9 15 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD NOV PY 2008 VL 92 IS 11 BP 1540 EP 1544 DI 10.1136/bjo.2008.141002 PG 5 WC Ophthalmology SC Ophthalmology GA 364MZ UT WOS:000260341100023 PM 18952656 ER PT J AU Rusby, JE Brachtel, EF Othus, M Michaelson, JS Koerner, FC Smith, BL AF Rusby, J. E. Brachtel, E. F. Othus, M. Michaelson, J. S. Koerner, F. C. Smith, B. L. TI Development and validation of a model predictive of occult nipple involvement in women undergoing mastectomy SO BRITISH JOURNAL OF SURGERY LA English DT Article ID SKIN-SPARING MASTECTOMY; BREAST-CANCER PATIENTS; AREOLA COMPLEX INVOLVEMENT; SUBCUTANEOUS MASTECTOMY; DUCT ANATOMY; RECONSTRUCTION; RISK; PRESERVATION; CARCINOMA AB Background: This prospective study aimed to build a predictive model using preoperative information to aid selection for nipple-sparing mastectomy. Methods: Two hundred consecutive skin-sparing mastectomy specimens without overt nipple involvement were evaluated. Demographic, preoperative pathology and imaging information was collected. Nipple specimens (2 x 2 x 2 cm) were sectioned at 3-mm intervals. Haematoxylin and eosin-stained slides were examined by a breast pathologist for involvement by turnout. Logistic regression analyses of 65 therapeutic procedures identified factors associated with occult involvement and created a predictive model. This was tested on specimens from a further 65 therapeutic procedures. Results: Occult nipple involvement was noted in 32 (24.6 per cent) of 130 mastectomy specimens. In the training set, imaging diameter of the lesion and its distance from the nipple predicted nipple involvement on univariable analysis (P = 0.011 and P = 0.014 respectively). The multivariable logistic regression model was validated in the test set. The areas under the receiver-operating characteristic curve were 0.824 and 0.709 for the training and test sets respectively. Conclusion: Three-quarters of women undergoing mastectomy did not have occult nipple involvement. A clinical tool including turnout size and distance from the nipple has been developed to improve patient selection for nipple-sparing mastectomy. C1 [Rusby, J. E.; Michaelson, J. S.; Smith, B. L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Brachtel, E. F.; Koerner, F. C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Othus, M.] Harvard Univ, Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org FU Philanthropic FX The authors thank Patricia Della Pelle and Nicole Brousaides for preparing sections, and Leon Chen for development of the accompanying web calculator. This study was supported financially by a philanthropic grant to B.L.S. NR 33 TC 47 Z9 49 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1323 EI 1365-2168 J9 BRIT J SURG JI Br. J. Surg. PD NOV PY 2008 VL 95 IS 11 BP 1356 EP 1361 DI 10.1002/bjs.6349 PG 6 WC Surgery SC Surgery GA 368II UT WOS:000260614400008 PM 18844271 ER PT J AU Hazra, A Fuchs, CS Chan, AT Giovannucci, EL Hunter, DJ AF Hazra, Aditi Fuchs, Charles S. Chan, Andrew T. Giovannucci, Edward L. Hunter, David J. TI Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk SO CANCER CAUSES & CONTROL LA English DT Article DE TCF7L2; polymorphism; WNT pathway; colorectal cancer; colorectal adenoma ID GENOME-WIDE ASSOCIATION; FACTOR BINDING PROTEIN-1; GLYCOSYLATED HEMOGLOBIN; INSULIN-RESISTANCE; BETA-CATENIN; C-PEPTIDE; GENE; VARIANT; WOMEN; TRANSCRIPTION AB We evaluated the association of a polymorphism in TCF7L2 (RS12255372) in the WNT signaling pathway, which previously has been strongly associated with risk of Type II Diabetes, with colorectal cancer (CRC) and adenoma in the prospective Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. Hyperinsulinemia may be related to the risk of colon adenoma and cancer, therefore this variant associated with reduced insulin secretion would be predicted to be inversely associated with colorectal cancer. Overall, in the NHS and HPFS, there was suggestive evidence for an inverse association associated with homozygosity for the minor allele of RS12255372 (TCF7L2 TT) and CRC (conditional and covariate adjusted OR = 0.63, 95% CI: 0.37-1.08; P for heterogeneity 0.52 for the association in women and men). In summary, the marginal association of the TCF7L2 SNP with CRC might be due to chance, but warrants further laboratory and epidemiological investigation. C1 [Hazra, Aditi; Fuchs, Charles S.; Chan, Andrew T.; Giovannucci, Edward L.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Hazra, Aditi; Fuchs, Charles S.; Chan, Andrew T.; Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hazra, Aditi; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Hazra, A (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM ahazra@hsph.harvard.edu FU National Institutes of Health [CA70817, CA87969, CA55075, T-32 CA 09001-30]; The Entertainment Industry Foundation National Colorectal Cancer Research Alliance (NCCRA). FX We thank Pati Soule, Hardeep Ranu, and Craig Labadie for their laboratory assistance. We are indebted to the dedicated participants of the Nurses' Health Study and the Health Professional Follow-up Study for their ongoing commitment. This research is supported by the National Institutes of Health Research Grants NIH: CA70817, CA87969, CA55075 and The Entertainment Industry Foundation National Colorectal Cancer Research Alliance (NCCRA). A. H. is supported in part by training grant NIH T-32 CA 09001-30. NR 30 TC 21 Z9 22 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2008 VL 19 IS 9 BP 975 EP 980 DI 10.1007/s10552-008-9164-3 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 351WR UT WOS:000259457100008 PM 18478343 ER PT J AU Miller, K Merry, B Miller, J AF Miller, Kenneth Merry, Brian Miller, Joan TI Seasons of Survivorship Revisited SO CANCER JOURNAL LA English DT Article DE cancer survivor; cancer survivorship; acute survivorship; transitional survivorship; extended cancer survivorship; permanent cancer survivorship ID CANCER AB Several decades ago the chance of a cancer survivor enjoying long-term survival was limited. At that time the terms cancer survivor and cancer survivorship were new. A cancer survivor was defined as a person from the moment of diagnosis onward for as long as they live. Cancer survivorship was also described in several "seasons" including: acute survivorship (the experience of diagnosis and treatment), extended survivorship (a time for "watchful waiting"). and then permanent survivorship (long-term remission). Today. acute cancer survivorship is still a time of intense emotion and medical activity Surrounding the diagnosis, staging, and actual treatment. We then propose that after the intense initial therapy is completed the survivors enter a "season" that can be called "transitional cancer survivorship" reflecting the transition from active treatment to careful observation and the emotional, social, and medical adaptations that occur. Next, there are a growing number of cancer survivors who are (1) alive and "living with cancer" but requiring ongoing treatment for recurrent, active, and often advanced disease: (2) in a complete remission that requires ongoing therapy: or (3) in a complete remission and with a favorable prognosis. Collectively. this is a diverse group in "extended survivorship" and some later go oil to obtain a permanent remission although others experience disease progression. Finally, there are millions of long-term or "permanent survivors." This group is also very heterogeneous and is comprised of 4 subgroups including (I) survivors who are "cancer-free but not free of cancer," (2) survivors who are cancer-free but continue to have significant "fall-out" from cancer and its treatment including psychosocial, medical, financial, or legal sequelae, (3) survivors who go oil to develop second cancers which may be unrelated to the first cancer or its treatment, or may be more likely due to genetic or environmental factors, and also (4) survivors who later develop cancers that are secondary to the initial treatment. C1 [Miller, Kenneth] Yale Canc Ctr, Dept Med Oncol, New Haven, CT USA. [Merry, Brian] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Miller, Joan] Cove Ctr Grieving Children, Meriden, CT USA. RP Miller, K (reprint author), Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. EM kenneth.d.miller@yale.edu NR 11 TC 22 Z9 22 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2008 VL 14 IS 6 BP 369 EP 374 DI 10.1097/PPO.0b013e31818edf60 PG 6 WC Oncology SC Oncology GA 382IY UT WOS:000261600700005 PM 19060601 ER PT J AU Ng, AK Travis, LB AF Ng, Andrea K. Travis, Lois B. TI Subsequent Malignant Neoplasms in Cancer Survivors SO CANCER JOURNAL LA English DT Article DE second malignant neoplasms; cancer survivorship; screening; prevention ID SURGICAL ADJUVANT BREAST; LONG-TERM SURVIVORS; ACUTE MYELOID-LEUKEMIA; SOFT-TISSUE SARCOMA; 2ND PRIMARY-CANCER; HODGKINS-DISEASE; RADIATION-THERAPY; CONTRALATERAL BREAST; TESTICULAR-CANCER; PROSTATE-CANCER AB In the past 3 decades, the number of cancer survivors in the United States has tripled, reaching approximately 10.7 million in 2004. Although cancer survivors now comprise about 3.5% of the population, subsequent malignancies among this high-risk group account for about 16% (or 1 in 6) of all cancer incidence. Multiple primary cancers call reflect the influence of antecedent cancer therapy. shared etiologic factors, environmental exposures, genetic susceptibility, lifestyle choices, other Factors, and file combinations of effects. including gene-environment and gene-gene interactions. Survivors of individual types of primary cancers are at increased risk for distinctive types of subsequent neoplasms. Careful documentation of the magnitude and temporal patterns of these site-specific excess risks. as well as delineation of the contribution of treatment exposures and other factors, will facilitate the development of optimal follow-up plans. Management approaches Should include patient education, screening, and prevention strategies. An improved understanding of those malignancies that are largely treatment-related will facilitate the formulation of customized therapeutic approaches for newly diagnosed cancer patients aimed at minimizing the risk of subsequent neoplasms and other late effects, without compromising cure rates. C1 [Ng, Andrea K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Travis, Lois B.] Univ Rochester, Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY USA. RP Ng, AK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 77 TC 32 Z9 34 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2008 VL 14 IS 6 BP 429 EP 434 DI 10.1097/PPO.0b013e31818d8779 PG 6 WC Oncology SC Oncology GA 382IY UT WOS:000261600700014 PM 19060610 ER PT J AU Wistuba, II Meyerson, M AF Wistuba, Ignacio I. Meyerson, Matthew TI Chromosomal Deletions and Progression of Premalignant Lesions: Less Is More SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID HUMAN LUNG-CANCER; MICROSATELLITE ALTERATIONS; HETEROZYGOSITY ANALYSIS; NEOPLASTIC PROGRESSION; BRONCHIAL EPITHELIUM; BARRETTS-ESOPHAGUS; BLADDER-CANCER; ALLELIC LOSS; FOCUS; CARCINOMA C1 [Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Unit 85, Houston, TX 77030 USA. [Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Meyerson, Matthew] Broad Inst Harvard, Cambridge, MA USA. [Meyerson, Matthew] MIT, Cambridge, MA 02139 USA. RP Wistuba, II (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pathol, Unit 85, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM iiwistuba@mdanderson.org; Matthew_Meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [P30 CA016672] NR 33 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD NOV PY 2008 VL 1 IS 6 BP 404 EP 408 DI 10.1158/1940-6207.CAPR-08-0177 PG 5 WC Oncology SC Oncology GA 420MM UT WOS:000264293900003 PM 19138986 ER PT J AU Stoffel, EM Turgeon, DK Stockwell, DH Zhao, L Normolle, DP Tuck, MK Bresalier, RS Marcon, NE Baron, JA Ruffin, MT Brenner, DE Syngal, S AF Stoffel, Elena M. Turgeon, D. Kim Stockwell, David H. Zhao, Lili Normolle, Daniel P. Tuck, Missy K. Bresalier, Robert S. Marcon, Norman E. Baron, John A. Ruffin, Mack T. Brenner, Dean E. Syngal, Sapna CA Great Lakes-New England Clin Epide TI Missed Adenomas during Colonoscopic Surveillance in Individuals with Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) SO CANCER PREVENTION RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; COLON-CANCER; PREVALENCE; CHROMOENDOSCOPY; NEOPLASIA; LESIONS; CHROMOSCOPY; POPULATION; ADULTS; RATES AB Background and Aims: Lynch syndrome (also known as hereditary nonpolyposis colon cancer) is associated with an increased risk for colorectal cancer, which can arise despite frequent colonoscopic exams. We evaluated the adenoma miss rate of conventional colonoscopy in patients with Lynch syndrome, and compared the sensitivity of chromoendoscopy versus intensive inspection for detecting polyps missed by conventional colonoscopy. Methods: Fifty-four subjects with Lynch syndrome underwent tandem colonoscopies at four centers of the Great Lakes- New England Clinical Epidemiology and Validation Center of the Early Detection Research Network. All participants first had a conventional colonoscopy with removal of all visualized polyps. The second endoscopy was randomly assigned as either pancolonic indigo carmine chromoendoscopy or standard colonoscopy with intensive inspection lasting >20 minutes. Size, histology, and number of polyps detected on each exam were recorded. Results: After undergoing standard colonoscopy, 28 individuals were randomized to a second exam with chromoendoscopy and 26 underwent intensive inspection. The mean interval since last colonoscopy was 17.5 months. Seventeen polyps (10 adenomas and 7 hyperplastic polyps) were identified on the first standard colonoscopies. Twenty-three additional polyps (12 adenomas and 11 hyperplastic polyps) were found on the second exams, yielding an adenoma miss rate of 55%. Fifteen polyps (5 adenomas and 10 hyperplastic polyps) were found in subjects who had chromoendoscopy and 8 polyps (7 adenomas and 1 hyperplastic polyp) in those who had intensive inspection. Chromoendoscopy was associated with more normal tissue biopsies (11 versus 5) and longer procedure times compared with intensive inspection (29.8 +/- 9.5 versus 25.3 +/- 5.8 minutes; P = 0.04). Controlling for age, number of previous colonoscopies, procedure time, and prior colonic resection, chromoendoscopy detected more polyps (P = 0.04), but adenoma detection was not significantly different compared with intensive inspection (P = 0.27). Conclusions: Small adenomas are frequently missed in patients with Lynch syndrome. Although chromoendoscopy did not detect more missed adenomas than intensive inspection in this pilot study, larger trials are needed to determine optimal surveillance techniques in this high-risk population. C1 [Stoffel, Elena M.] Brigham & Womens Hosp, Div Gastroenterol, Dana Farber Harvard Canc Inst, Boston, MA 02115 USA. [Turgeon, D. Kim; Tuck, Missy K.; Ruffin, Mack T.; Brenner, Dean E.] Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. [Zhao, Lili] Univ Michigan, Ctr Comprehens Canc, Biostat Unit, Ann Arbor, MI 48109 USA. [Normolle, Daniel P.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Bresalier, Robert S.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Marcon, Norman E.] Wellesley Site St Michaels Hosp, Toronto, ON, Canada. [Baron, John A.] Dartmouth Med Sch, Lebanon, NH USA. RP Stoffel, EM (reprint author), Brigham & Womens Hosp, Div Gastroenterol, Dana Farber Harvard Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM estoffel@partners.org OI Normolle, Daniel/0000-0001-8675-5014; Ruffin, Mack/0000-0001-8336-478X FU NCI [CA 86400, P30 CA46592, K24 CA113433]; Early Detection Research Network; American Society for Gastrointestinal Endoscopy ASGE 2006 Research Outcomes and Effectiveness Award; [, NIH-NCI K07 CA 120448-01-A2] FX NCI grant CA 86400 Early Detection Research Network, NIH-NCI K07 CA 120448-01-A2 (E. Stoffel), American Society for Gastrointestinal Endoscopy ASGE 2006 Research Outcomes and Effectiveness Award (E. Stoffel), NCI grant P30 CA46592 (L. Zhao), and NCI grant K24 CA113433 (S. Syngal). NR 22 TC 47 Z9 47 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD NOV PY 2008 VL 1 IS 6 BP 470 EP 475 DI 10.1158/1940-6207.CAPR-08-0098 PG 6 WC Oncology SC Oncology GA 420MM UT WOS:000264293900011 PM 19138994 ER PT J AU Jinushi, M Nakazaki, Y Carrasco, DR Draganov, D Souders, N Johnson, M Mihm, MC Dranoff, G AF Jinushi, Masahisa Nakazaki, Yukoh Carrasco, Daniel R. Draganov, Dobrin Souders, Nicholas Johnson, Matthew Mihm, Martin C. Dranoff, Glenn TI Milk Fat Globule EGF-8 Promotes Melanoma Progression through Coordinated Akt and Twist Signaling in the Tumor Microenvironment SO CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; NF-KAPPA-B; APOPTOTIC CELLS; ANTITUMOR IMMUNITY; METASTATIC MELANOMA; MALIGNANT-MELANOMA; CANCER DEVELOPMENT; EXPRESSION; INFLAMMATION; VACCINATION AB The pathogenesis of malignant melanoma involves the interplay of tumor cells with normal host elements, but the underlying mechanisms are incompletely understood. Here, we show that milk fat globule EGF-8 (MFG-E8), a secreted protein expressed at high levels in the vertical growth phase of melanoma, promotes disease progression through coordinated alpha(v)beta(3) integrin signaling in the tumor microenvironment. In a murine model of melanoma, MFG-E8 enhanced tumorigenicity and metastatic capacity through Akt-dependent and Twist-dependent pathways. MFG-E8 augmented melanoma cell resistance to apoptosis, triggered an epithelial-to-mesenchymal transition (EMT), and stimulated invasion and immune suppression. In human melanoma cells, MFG-E8 knockdown attenuated Akt and Twist signaling and thereby compromised tumor cell survival, EMT, and invasive ability. MFG-E8-deficient human melanoma cells also showed increased sensitivity to small molecule inhibitors of insulin-like growth factor I receptor and c-Met. Together, these findings delineate pleiotropic roles for MFG-E8 in the tumor microenvironment and raise the possibility that systemic MFG-E8 blockade might prove therapeutic for melanoma patients. [Cancer Res 2008;68(21.):8889-98] C1 [Jinushi, Masahisa; Nakazaki, Yukoh; Carrasco, Daniel R.; Draganov, Dobrin; Souders, Nicholas; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jinushi, Masahisa; Nakazaki, Yukoh; Carrasco, Daniel R.; Draganov, Dobrin; Souders, Nicholas; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Jinushi, Masahisa; Nakazaki, Yukoh; Carrasco, Daniel R.; Draganov, Dobrin; Souders, Nicholas; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Carrasco, Daniel R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jinushi, Masahisa; Nakazaki, Yukoh; Carrasco, Daniel R.; Draganov, Dobrin; Souders, Nicholas; Johnson, Matthew; Mihm, Martin C.; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Matthew; Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Jinushi, Masahisa] Univ Tokyo, Inst Med Sci, Dept Bioengn, Adv Clin Res Ctr, Tokyo, Japan. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu RI Jinushi, Masahisa/A-4311-2012 FU Uehara Memorial Foundation; Kanae Foundation [CA78378, CA111506, Al29530] FX Uehara Memorial Foundation, Kanae Foundation for the Promohon of Medical Sciences (M. Jinushi), CA78378, CA111506, Al29530, Leukemia and Lymphoma Society, Melanoma Research Alliance, and Research Foundation for the Treatment of Ovarian Cancer (G. Dranoff.). NR 50 TC 47 Z9 51 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2008 VL 68 IS 21 BP 8889 EP 8898 DI 10.1158/0008-5472.CAN-08-2147 PG 10 WC Oncology SC Oncology GA 369MP UT WOS:000260698900031 PM 18974133 ER PT J AU Neklason, DW Kerber, RA Nilson, DB Anton-Culver, H Schwartz, AG Griffin, CA Lowery, JT Schildkraut, JM Evans, JP Tomlinson, GE Strong, LC Miller, AR Stopfer, JE Finkelstein, DM Nadkarni, PM Kasten, CH Mineau, GP Burt, RW AF Neklason, Deborah W. Kerber, Richard A. Nilson, David B. Anton-Culver, Hoda Schwartz, Ann G. Griffin, Constance A. Lowery, Jan T. Schildkraut, Joellen M. Evans, James P. Tomlinson, Gail E. Strong, Louise C. Miller, Alexander R. Stopfer, Jill E. Finkelstein, Dianne M. Nadkarni, Prakash M. Kasten, Carol H. Mineau, Geraldine P. Burt, Randall W. TI Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis SO CANCER RESEARCH LA English DT Article ID SUSCEPTIBILITY LOCUS; ASSOCIATION SCAN; LINKAGE; GENES; KINDREDS; ERBB4; TESTS; RISK; 8Q24; MAP AB Present investigations suggest that similar to 30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high-grade dysplasia were enrolled. Known familial colorectal cancer syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE 1100 short tandem repeat marker set at an average 4-cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with Merlin analysis package. Nonparametric linkage analysis revealed three genetic regions with logarithm of the odds (LOD) scores >= 2.0: Ch. 3q29, LOD 2.61 (P = 0.0003); Ch. 4q31.3, LOD 2.13 (P = 0.0009); and Ch. 7q31.31, LOD 3.08 (P = 0.00008). Affected siblings with increased sharing at the 7q31 locus have a 3.8-year (+/- 3.5) earlier age of colorectal cancer onset although this is not statistically significant (P = 0.11). No significant linkage was found near genes causing known syndromes or regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21-q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak (LOD 0.9; P = 0.02). No known familial cancer genes reside in the 7q31 locus, and thus the identified region may contain a novel susceptibility gene responsible for common familial colorectal cancer. [Cancer Res 2008;68(21):8993-7] C1 [Neklason, Deborah W.; Kerber, Richard A.; Nilson, David B.; Mineau, Geraldine P.; Burt, Randall W.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Anton-Culver, Hoda] Univ Calif Irvine, Irvine, CA USA. [Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Griffin, Constance A.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Griffin, Constance A.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Lowery, Jan T.] Colorado Sch Publ Hlth, Denver, CO USA. [Schildkraut, Joellen M.] Duke Univ, Durham, NC USA. [Evans, James P.] Univ N Carolina, Chapel Hill, NC USA. [Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Strong, Louise C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Miller, Alexander R.] Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. [Miller, Alexander R.] Univ Texas San Antonio, San Antonio, TX USA. [Stopfer, Jill E.] Univ Penn, Philadelphia, PA 19104 USA. [Finkelstein, Dianne M.] Massachusetts Gen Hosp, Stat Coordinating Ctr, Boston, MA 02114 USA. [Nadkarni, Prakash M.] Yale Ctr Informat, New Haven, CT USA. [Kasten, Carol H.] NCI, Rockville, MD USA. RP Neklason, DW (reprint author), Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84112 USA. EM Deb.neklason@hci.utah.edu RI Kerber, Richard/B-8038-2009 FU NIH [U24-CA78174, P01-CA073992, U24-CA78134, U01-CA78285, N01-PC35145, U24-CA78148, CA74799, U24-CA78142, CA78157-05S1, U01-CA078284]; University of Utah General Clinical Research Center [M01-RR00064, N01-PC-67000]; National Cancer Institute Surveillance, Epidemiology, and End Results; Utah State Department of Health; University of Utah; Huntsman Cancer Foundation FX NIH grants U24-CA78174 (G.P. Mineau), P01-CA073992 (RAV. Burt), U24-CA78134 (H. Anton-Culver), U01-CA78285 (H. Anton-Culver), N01-PC35145 (A.G. Schwartz), U24-CA78148 (C.A. Griffin), CA74799 (J.T. Lowery), U24-CA78142 (I-C. Strong), CA78157-05S1 (J.E. Stopfer), and U01-CA078284 (D.M. Finkelstein); University of Utah General Clinical Research Center grants M01-RR00064 and N01-PC-67000; Utah Cancer Registry grant. N01-PC-35141 from the National Cancer Institute Surveillance, Epidemiology, and End Results program; the Utah State Department of Health; and the University of Utah, Huntsman Cancer Foundation. NR 26 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2008 VL 68 IS 21 BP 8993 EP 8997 DI 10.1158/0008-5472.CAN-08-1376 PG 5 WC Oncology SC Oncology GA 369MP UT WOS:000260698900042 PM 18974144 ER PT J AU Coleman, R Brown, J Terpos, E Lipton, A Smith, MR Cook, R Major, P AF Coleman, Robert Brown, Janet Terpos, Evangelos Lipton, Allan Smith, Matthew R. Cook, Richard Major, Pierre TI Bone markers and their prognostic value in metastatic bone disease: Clinical evidence and future directions SO CANCER TREATMENT REVIEWS LA English DT Review DE Bone alkaline phosphatase; Bone sialoprotein; C-telopeptide of type I collagen; N-telopeptide of type I collagen; Osteoprotegerin ID BREAST-CANCER PATIENTS; RESISTANT ACID-PHOSPHATASE; KAPPA-B LIGAND; ADVANCED MULTIPLE-MYELOMA; PYRIDINIUM CROSS-LINKS; ZOLEDRONIC ACID; BIOCHEMICAL MARKERS; I COLLAGEN; SKELETAL COMPLICATIONS; RECEPTOR ACTIVATOR AB Background: Bone metastases are prevalent among patients with advanced solid tumors. Metastatic bone disease alters; bone homeostasis, resulting in reduced bone integrity and, consequently, increased skeletal. complications. Biochemical markers of bone metabolism may meet an unmet need for useful, noninvasive, and sensitive surrogate information for following patients' skeletal health. Materials and methods: Data for this review were identified by searches of PubMed, and references from relevant articles using the search terms "bone markers" or individual bone marker nomenclature, "cancer," and "metastases." Abstracts and reports from meetings were included only when they related directly to previously published work. Only papers published in English between 1990 and 2007 were included. Results: Recent retrospective analyses with bisphosphonates, and particularly with zoledronic acid, have shown significant correlations between biochemical markers of bone metabolism levels and clinical outcomes, especially for bone resorption markers. Clinical results for biochemical markers of bone formation and resorption and other emerging markers of bone metabolism including bone sialoprotein, receptor-activator of nuclear factor-kappa B Ligand, osteoprotegerin, and other markers are presented. However, biochemical markers of bone metabolism are not yet an established surrogate endpoint for treatment efficacy. Conclusions: Biochemical markers of bone metabolism may allow physicians to identify which patients with metastatic bone disease are at high risk for skeletal-related events or death and who may be responding to therapy. Prospective randomized clinical trials are underway to further assess the utility of markers of bone metabolism in patients with bone metastases. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Coleman, Robert] Weston Pk Hosp, Canc Res Ctr, Acad Unit Clin Oncol, Sheffield S10 2SJ, S Yorkshire, England. [Brown, Janet] Univ Leeds, St James Hosp, Canc Res UK Clin Ctr, Leeds LS9 7TF, W Yorkshire, England. [Terpos, Evangelos] 251 Gen AF Hosp, Dept Hematol & Med Res, GR-11525 Athens, Greece. [Lipton, Allan] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Cook, Richard] Univ Waterloo, Waterloo, ON N2L 3G1, Canada. [Major, Pierre] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON L8V 5C2, Canada. RP Coleman, R (reprint author), Weston Pk Hosp, Canc Res Ctr, Acad Unit Clin Oncol, Sheffield S10 2SJ, S Yorkshire, England. EM R.E.Coleman@sheffield.ac.uk; j.e.brown@leeds.ac.uk; eterpos@hotmail.com; alipton@psu.edu; smith.matthew@mgh.harvard.edu; rjcook@uwaterloo.ca; Pierre.Major@hrcc.on.ca FU Cancer Research UK [10048]; NCI NIH HHS [K24 CA121990, K24 CA121990-02, K24 CA121990-03] NR 90 TC 67 Z9 69 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD NOV PY 2008 VL 34 IS 7 BP 629 EP 639 DI 10.1016/j.ctrv.2008.05.001 PG 11 WC Oncology SC Oncology GA 370KQ UT WOS:000260761500006 PM 18579314 ER PT J AU Ter-Minassian, M Zhai, RH Asomaning, K Su, L Zhou, W Liu, G Heist, RS Lynch, TJ Wain, JC Lin, XH DeVivo, I Christiani, DC AF Ter-Minassian, Monica Zhai, Rihong Asomaning, Kofi Su, Li Zhou, Wei Liu, Geoffrey Heist, Rebecca Suk Lynch, Thomas J. Wain, John C. Lin, Xihong DeVivo, Immaculata Christiani, David C. TI Apoptosis gene polymorphisms, age, smoking and the risk of non-small cell lung cancer SO CARCINOGENESIS LA English DT Article ID FAS LIGAND GENES; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CIGARETTE-SMOKING; DEATH PATHWAY; FUNCTIONAL POLYMORPHISMS; INTERLEUKIN-1-BETA GENE; PROMOTER REGION; CERVICAL-CANCER; BREAST-CANCER; LYMPHOCYTES AB Apoptosis is important for targeting cancer cells for destruction. Various single-nucleotide polymorphisms (SNPs) in apoptotic genes have been associated with increased risks in lung cancer, particularly FAS -1377 G > A (rs2234767), FASLG -844 C > T (rs763110), IL1B +3954 C > T Phe105Phe (rs1143634) and BAT3 Ser625Pro (rs1052486). We studied the association of these SNPs with non-small cell lung cancer (NSCLC) in a large case-control study (N = 4263: 2644 cases and 1619 controls). No associations with NSCLC were observed in the main effects analysis for all four SNPs, adjusting for age, gender, smoking status, pack-years and years since smoking cessation. In subjects under age 60, for FASLG -844 C > T polymorphism, CT compared with the CC genotype, was significantly associated with increased risk of NSCLC, adjusted odds ratio (aOR) = 1.58 (1.22, 2.05), P = 0.0006 and TT aOR = 1.45 (1.01, 2.04), P = 0.04. In contrast, for those over age 60, the CT aOR = 0.91 (0.73, 1.13), P = 0.37 and TT aOR = 0.86 (0.64, 1.16), P = 0.32. The P-value for the age-genotype interaction was 0.004. For the IL1B +3954 C > T polymorphism, compared with the CC genotype, TT showed significant associations in former smokers and in men but tests of interaction were not significant (P-smoking = 0.24, P-gender = 0.17). No interactions were observed for FAS -1377 G > A and BAT3 Ser625Pro polymorphisms. Our findings indicate that age and smoking may modify the association of the FASLG -844 and IL1B + 3954 SNPs with the risk of NSCLC. C1 [Ter-Minassian, Monica; Zhai, Rihong; Asomaning, Kofi; Su, Li; Zhou, Wei; Heist, Rebecca Suk; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Wain, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thorac Surg Unit,Dept Med, Boston, MA 02114 USA. [Lynch, Thomas J.; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Liu, Geoffrey; Heist, Rebecca Suk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [DeVivo, Immaculata; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Appl Mol Oncol & Dept Med Oncol, Toronto, ON M5G 2M9, Canada. RP Ter-Minassian, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM mtermina@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU National Institutes of Health [CA074386]; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health [T42-OH008416]; Flight Attendant Medical Research Institute [062459_YCSA]; Virginia B. Taplin Scholarship Fund FX National Institutes of Health (CA074386); Centers for Disease Control and Prevention/The National Institute for Occupational Safety and Health (T42-OH008416); Flight Attendant Medical Research Institute (062459_YCSA); John F. and Virginia B. Taplin Scholarship Fund. NR 40 TC 42 Z9 45 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2008 VL 29 IS 11 BP 2147 EP 2152 DI 10.1093/carcin/bgn205 PG 6 WC Oncology SC Oncology GA 373NE UT WOS:000260977900014 PM 18757527 ER PT J AU Xiang, N Zhao, R Song, GQ Zhong, WX AF Xiang, Nong Zhao, Rui Song, Guoqing Zhong, Weixiong TI Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells SO CARCINOGENESIS LA English DT Article ID CYTOSINE METHYLATION; PROTECTIVE ROLE; LIVER-CANCER; METHYLTRANSFERASE; PREVENTION; HYPERMETHYLATION; EXPRESSION; PROGNOSIS; DIAGNOSIS; BIOPSIES AB DNA hypermethylation is a common epigenetic alteration in human prostate cancer and is considered to contribute to development of this disease. Accumulating data suggest that dietary factors may alter cancer risk by modifications of epigenetic processes in the cell. The present study was designed to investigate whether selenium (Se) would alter epigenetic events to regulate methylation-silenced genes in human prostate cancer cells. DNA methylation, histone modifications and gene expression were studied in LNCaP cells after selenite treatment using polymerase chain reaction, western blot analysis, chromatin immunoprecipitation assay and enzymatic activity assay. Our study shows that selenite treatment caused partial promoter DNA demethylation and reexpression of the pi-class glutathione-S-transferase (GSTP1) in LNCaP cells in a dose- and time-dependent manner. Selenite treatment decreased messenger RNA levels of DNA methyltransferases (DNMTs) 1 and 3A and protein levels of DNMT1. Selenite also decreased histone deacetylase activity and increased levels of acetylated lysine 9 on histone H3 (H3-Lys 9), but decreased levels of methylated H3-Lys 9. Selenite treatment reduced levels of DNMT1 and methylated H3-Lys 9 associated with the GSTP1 promoter, but increased levels of acetylated H3-Lys 9 associated with this promoter. Additionally, selenite treatment decreased general DNA methylation and caused partial promoter demethylation and reexpression of the tumor suppressor adenomatous polyposis coli and cellular stress response 1, a gene involving tumor growth and metastasis. Our study demonstrates that Se can epigenetically modulate DNA and histones to activate methylation-silenced genes. These epigenetic modifications may contribute to cancer prevention by Se. C1 [Xiang, Nong; Zhao, Rui; Song, Guoqing; Zhong, Weixiong] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA. [Zhong, Weixiong] William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med Serv, Madison, WI 53705 USA. RP Zhong, WX (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA. EM wzhong3@wisc.edu FU National Cancer Institute [CA114281]; Office of Research and Development; Biomedical Laboratory Research and Development Service; Department of Veterans Affairs FX National Cancer Institute (CA114281); Office of Research and Development, Biomedical Laboratory Research and Development Service, Department of Veterans Affairs. NR 37 TC 73 Z9 75 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2008 VL 29 IS 11 BP 2175 EP 2181 DI 10.1093/carcin/bgn179 PG 7 WC Oncology SC Oncology GA 373NE UT WOS:000260977900018 PM 18676679 ER PT J AU Wildgruber, M Berger, H AF Wildgruber, Moritz G. Berger, Hermann J. TI Cryoplasty for the Prevention of Arterial Restenosis SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review DE Cryoplasty; Angioplasty; Restenosis; Neointimal hyperplasia; Infrainguinal arteries ID SUPERFICIAL FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; SMOOTH-MUSCLE-CELLS; HUMAN FEMOROPOPLITEAL ARTERY; CRITICAL LIMB ISCHEMIA; DRUG-ELUTING STENTS; RAT CAROTID-ARTERY; BALLOON ANGIOPLASTY; FOLLOW-UP; ENDOVASCULAR BRACHYTHERAPY AB Restenosis after percutaneous transluminal angioplasty remains the limiting factor for the long-term benefit of endovascular therapies of peripheral arterial occlusive disease. Despite a variety of modifications and adjuncts to angioplasty such as bare metal stents, covered stents, and drug-eluting stents as well as a number of new technologies like laser angioplasty and cutting balloon angioplasty, restenosis rates have not been significantly affected and remain inferior to those for surgery for long lesions in the femoropopliteal segment. Cryoplasty, which combines balloon angioplasty with the application of cryothermal energy to the vessel wall, was suggested as a promising approach to prevent the formation of neointimal hyperplasia after angioplasty procedures. This review discusses the basic principles of cryoplasty, summarizes the current data on restenosis rates after cryoplasty treatment, and evaluates cryoplasty as a new treatment method to solve the problems associated with restenosis development. The results of the clinical studies suggest that cryoplasty is a feasible and safe technique in the treatment of femoropopliteal disease, however, they have failed to prove any superiority of cryoplasty over conventional angioplasty. C1 [Wildgruber, Moritz G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Berger, Hermann J.] Tech Univ Munich, Dept Intervent Radiol, Rechts Isar Med Ctr, D-81675 Munich, Germany. RP Wildgruber, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 13th St,Bldg 149, Boston, MA 02129 USA. EM wildgruber.moritz@mgh.harvard.edu NR 68 TC 11 Z9 13 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD NOV PY 2008 VL 31 IS 6 BP 1050 EP 1058 DI 10.1007/s00270-008-9364-y PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 370MN UT WOS:000260766400001 PM 18535858 ER PT J AU Hussein, MR Abu-Dief, EE Kamel, E Abou El-Ghait, AT Abdulwahed, SR Ahmad, MH AF Hussein, Mahmoud R. Abu-Dief, Eman E. Kamel, Esam Abou El-Ghait, Amal T. Abdulwahed, Saad Rezk Ahmad, Mohamed H. TI Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: An animal model SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE Intestine; X-ray irradiation; Melatonin ID X-RAY-IRRADIATION; DAMAGE; GLUTAMINE; TESTIS; CELLS; ORGAN AB Background: Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking. Hypothesis: This study tries to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis". Objectives and methods: We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (X-ray irradiation, 8 Grays); Group 3, X-ray irradiated-pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non-irradiated-group treated with melatonin, and Group 5, X-ray irradiated-pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy). Results: We found morphological variations among the non-irradiated-group, X-ray irradiated-group and X-ray irradiated-intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X-ray irradiated-group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural features of cell damage were evident including: apoptosis, lack of parallel arrangement of the microvilli, loss of the covering glycocalyx, desquamation of the microvilli, vacuolation of the apical parts of the cells, dilatation of the rough endoplasmic reticulum, and damage of the mitochondrial cristae. In the non-irradiated-group and in X-ray irradiated-intestines of the animals pretreated with melatonin (Group 5), these changes were absent and the intestinal mucosal structure was preserved. Conclusion: Administration of melatonin prior to irradiation can protect the intestine against X-rays destructive effects, i.e. radiation enteritis. The clinical applications of these observations await further studies. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. C1 [Hussein, Mahmoud R.] Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. [Abu-Dief, Eman E.; Abou El-Ghait, Amal T.; Ahmad, Mohamed H.] Assiut Univ, Fac Med, Dept Histol, Assiut, Egypt. [Abdulwahed, Saad Rezk] Al Azhar Univ, Fac Med, Dept Radiol, Assiut, Egypt. [Hussein, Mahmoud R.] Univ Wisconsin, Sch Med, Madison, WI 53705 USA. [Hussein, Mahmoud R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Hussein, MR (reprint author), Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. EM mrh17@gawab.com NR 23 TC 11 Z9 16 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD NOV PY 2008 VL 32 IS 11 BP 1353 EP 1361 DI 10.1016/j.cellbi.2008.08.001 PG 9 WC Cell Biology SC Cell Biology GA 369CU UT WOS:000260671900003 PM 18762261 ER PT J AU Witczak, CA Sharoff, CG Goodyear, LJ AF Witczak, C. A. Sharoff, C. G. Goodyear, L. J. TI AMP-activated protein kinase in skeletal muscle: From structure and localization to its role as a master regulator of cellular metabolism SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Ca2+; calmodulin-dependent protein kinase kinase; carbohydrate; glucose; lipid; LKB1; protein phosphatase; transforming growth factor-beta-activated kinase 1 ID ACETYL-COA CARBOXYLASE; FOXO TRANSCRIPTION FACTORS; HORMONE-SENSITIVE LIPASE; STIMULATED GLUCOSE-TRANSPORT; JEGHERS CANCER SYNDROME; FATTY-ACID OXIDATION; MOLECULAR-CLONING; YEAST SNF1; RAT-LIVER; SIGNALING PATHWAYS AB The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include the following: (1) the structural components of the three AMPK subunits (i.e. AMPK alpha, beta, and gamma), and their differential localization in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-beta-activated kinase 1 (TAK1); (3) the pharmacological agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle. C1 [Witczak, C. A.; Goodyear, L. J.] Joslin Diabet Ctr, Div Res, Metab Sect, Boston, MA 02215 USA. [Sharoff, C. G.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu NR 164 TC 114 Z9 118 U1 2 U2 18 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2008 VL 65 IS 23 BP 3737 EP 3755 DI 10.1007/s00018-008-8244-6 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 379MZ UT WOS:000261401900003 PM 18810325 ER PT J AU Hinds, O Polimeni, JR Rajendran, N Balasubramanian, M Wald, LL Augustinack, JC Wiggins, G Rosas, HD Fischl, B Schwartz, EL AF Hinds, Oliver Polimeni, Jonathan R. Rajendran, Niranjini Balasubramanian, Mukund Wald, Lawrence L. Augustinack, Jean C. Wiggins, Graham Rosas, H. Diana Fischl, Bruce Schwartz, Eric L. TI The Intrinsic Shape of Human and Macaque Primary Visual Cortex SO CEREBRAL CORTEX LA English DT Article DE correlated variability; cortical area development; myelin; striate cortex; visual topography ID PRIMARY AUDITORY-CORTEX; EXTRA-STRIATE CORTEX; CEREBRAL-CORTEX; HUMAN BRAIN; INTERINDIVIDUAL VARIABILITY; INTERSUBJECT VARIABILITY; FIELD REPRESENTATION; ALZHEIMERS-DISEASE; HUNTINGTON-DISEASE; STEREOTAXIC SPACE AB Previous studies have reported considerable variability in primary visual cortex (V1) shape in both humans and macaques. Here, we demonstrate that much of this variability is due to the pattern of cortical folds particular to an individual and that V1 shape is similar among individual humans and macaques as well as between these 2 species. Human V1 was imaged ex vivo using high-resolution (200 mu m) magnetic resonance imaging at 7 T. Macaque V1 was identified in published histological serial section data. Manual tracings of the stria of Gennari were used to construct a V1 surface, which was computationally flattened with minimal metric distortion of the cortical surface. Accurate flattening allowed investigation of intrinsic geometric features of cortex, which are largely independent of the highly variable cortical folds. The intrinsic shape of V1 was found to be similar across human subjects using both nonparametric boundary matching and a simple elliptical shape model fit to the data and is very close to that of the macaque monkey. This result agrees with predictions derived from current models of V1 topography. In addition, V1 shape similarity suggests that similar developmental mechanisms are responsible for establishing V1 shape in these 2 species. C1 [Hinds, Oliver] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Hinds, Oliver; Balasubramanian, Mukund; Schwartz, Eric L.] Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. [Polimeni, Jonathan R.; Rajendran, Niranjini; Wald, Lawrence L.; Augustinack, Jean C.; Wiggins, Graham; Fischl, Bruce; Schwartz, Eric L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. [Polimeni, Jonathan R.] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Rosas, H. Diana] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Athinoula A Martinos Ctr,Med Sch, Charlestown, MA 02129 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Schwartz, Eric L.] Boston Univ, Dept Anat & Neurobiol, Sch Med, Boston, MA 02215 USA. RP Hinds, O (reprint author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave,46-5081, Cambridge, MA 02139 USA. EM ohinds@mit.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU National Institute for Biomedical Imaging and Bioengineering [R01 EB001550]; Massachusetts Alzheimer's Disease Research Center [P50 AG05134]; National Center for Research Resources [P41 RR14075, R01 RR16594, BIRN002, U24 RR021382]; National Institute for Neurological Disorders and Stroke [R01 NS052585]; Mental Illness and Neuroscience Discovery Institute; National Institutes of Health [U54 EB005149] FX National Institute for Biomedical Imaging and Bioengineering (R01 EB001550); Massachusetts Alzheimer's Disease Research Center grant (P50 AG05134); the National Center for Research Resources (P41 RR14075, R01 RR16594, the National Center for Research Resources Biomedical Informatics Research Network Morphometric Project BIRN002, U24 RR021382); the National Institute for Neurological Disorders and Stroke (R01 NS052585); the Mental Illness and Neuroscience Discovery Institute. This work is part of the National Alliance for Medical Image Computing, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant U54 EB005149. NR 85 TC 17 Z9 17 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2008 VL 18 IS 11 BP 2586 EP 2595 DI 10.1093/cercor/bhn016 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 361NZ UT WOS:000260135700011 PM 18308709 ER PT J AU Wright, RJ Suglia, SF Levy, J Fortun, K Shields, A Subramanian, SV Wright, R AF Wright, Rosalind J. Suglia, Shakira Franco Levy, Jonathan Fortun, Kim Shields, Alexandra Subramanian, S. V. Wright, Robert TI Transdisciplinary research strategies for understanding socially patterned disease: the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project as a case study SO CIENCIA & SAUDE COLETIVA LA English DT Article DE Asthma disparities; Transdisciplinary; Social epidemiology; Multilevel ID TIMELINE FOLLOW-BACK; SOCIOECONOMIC-STATUS; PARTICULATE MATTER; HEALTH DISPARITIES; CHILDHOOD ASTHMA; NITROGEN-DIOXIDE; HOST-RESISTANCE; AIR-POLLUTION; VIOLENCE; LIFE AB As we have seen a global increase in asthma in the past three decades it has also become clear that it is a socially patterned disease, based on demographic and socioeconomic indicators clustered by areas of residence. This trend is not readily explained by traditional genetic paradigms or physical environmental exposures when considered alone. This has led to consideration of the interplay among physical and psychosocial environmental hazards and the molecular and genetic determinants of risk (i.e., biomedical framing) within the broader socioenvironmental context including socioeconomic position as an upstream "cause of the causes" (i. e., ecological framing). Transdisciplinary research strategies or programs that embrace this complexity through a shared conceptual framework that integrates diverse discipline-specific theories, models, measures, and analytical methods into ongoing asthma research may contribute most significantly toward furthering our understanding of socially patterned disease. This paper provides an overview of a multilevel, multimethod longitudinal study, the Asthma Coalition on Community, Environment and Social Stress (ACCESS), as a case study to exemplify both the opportunities and challenges of transdisciplinary research on urban asthma expression in the United States. C1 [Wright, Rosalind J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Wright, Rosalind J.; Suglia, Shakira Franco; Levy, Jonathan; Wright, Robert] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Fortun, Kim] Rensselaer Polytech Inst, Dept Sci & Technol Studies, Troy, NY 12181 USA. [Shields, Alexandra] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Wright, RJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM rosalind.wright@channing.harvard.edu RI Levy, Jonathan/A-9102-2008; Levy, Jon/B-4542-2011 OI Levy, Jon/0000-0002-1116-4006 FU NHLBI NIH HHS [R01 HL080674-02, K25 HL081275, R01 HL080674]; NIEHS NIH HHS [R01 ES010932, R01 ES010932-05]; NIMH NIH HHS [T32 MH073122]; NIMHD NIH HHS [R01 MD006086] NR 78 TC 28 Z9 28 U1 2 U2 8 PU ABRASCO PI RIO DE JANEIRO PA RUA HESPERIA, 16-PARTE MANGUINHOS, RIO DE JANEIRO, 21050-040, BRAZIL SN 1413-8123 J9 CIENC SAUDE COLETIVA JI Cienc. Saude Coletiva PD NOV-DEC PY 2008 VL 13 IS 6 BP 1729 EP 1742 DI 10.1590/S1413-81232008000600008 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385QN UT WOS:000261828800008 PM 18833350 ER PT J AU Wolpin, S Berry, D Austin-Seymour, M Bush, N Fann, JR Halpenny, B Lober, WB McCorkle, R AF Wolpin, Seth Berry, Donna Austin-Seymour, Mary Bush, Nigel Fann, Jesse R. Halpenny, Barbara Lober, William B. McCorkle, Ruth TI Acceptability of an Electronic Self-report Assessment Program for Patients With Cancer SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article DE Internet; Quality of life; Survey methods ID ONCOLOGY AB Eliciting symptom and quality of life information from patients is an important component of medical and nursing care processes. Traditionally, this information has been collected with paper and pencil. However, this approach presents several barriers, including delays in receiving information, difficulty in integrating responses with electronic records, and the time required to manually score questionnaires for measurement purposes. One solution that addresses many of these barriers is the adoption of computerized screening for symptom and quality-of-life information. This research explored the acceptability of asking symptom and quality-of-life questions using the Electronic Self Report Assessment-Cancer program on wireless laptops equipped with touch-screen format. Acceptability data were explored with respect to whether any differences may be attributed to demographics and symptom and quality-of-life levels, such as depression and cognitive and emotional functioning. This evaluation used descriptive and univariate statistics to examine data from 342 participants from the ongoing ESRA-C randomized clinical trial. Research participants for the ESRA-C study were recruited from the Seattle Cancer Care Alliance, a consortium among the University of Washington Medical Center, Fred Hutchinson Cancer Research Center, and Children's Hospital and Regional Medical Center in Seattle, WA. The sample consisted of 342 adult participants who completed both baseline and follow-up survey sessions. Medical oncology represented the largest recruitment group (45.3%), followed by stem cell transplant (34.5%) and radiation oncology (20.2%). The primary finding was that patients were generally able to use ESRA-C quickly and without difficulty in a real-world clinical setting and that they were overall quite satisfied with the ESRA-C program. Significant differences were found in several acceptability areas with respect to demographics and quality of life measures such as age, sex, and severe distress. This analysis confirms that the ESRA-C application for collecting symptom and quality of life information is easy for patients to use and acceptable across a range of user characteristics. We intend to build on our work by using the survey platform in other modalities while ensuring that the patient's preferences are considered at all times. C1 [Wolpin, Seth; Berry, Donna; Halpenny, Barbara; Lober, William B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Berry, Donna] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Austin-Seymour, Mary; Lober, William B.] Univ Washington, Sch Med, Seattle, WA USA. [Lober, William B.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [McCorkle, Ruth] Yale Univ, Boston, MA USA. [Berry, Donna; Halpenny, Barbara] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wolpin, S (reprint author), Univ Washington Biobehav Nursing & Hlth Syst, 1959 NE Pacific St,Box 357266, Seattle, WA 98195 USA. EM swolpin@u.washington.edu FU National Institute of Nursing Research [R01 NR 008726] FX This study was funded by the National Institute of Nursing Research: R01 NR 008726 NR 15 TC 22 Z9 23 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD NOV-DEC PY 2008 VL 26 IS 6 BP 332 EP 338 DI 10.1097/01.NCN.0000336464.79692.6a PG 7 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 371VD UT WOS:000260858900003 PM 19047882 ER PT J AU Derumeaux, G Ichinose, F Raher, MJ Morgan, JG Coman, T Lee, C Cuesta, JM Thibault, H Bloch, KD Picard, MH Scherrer-Crosbie, M AF Derumeaux, Genevieve Ichinose, Fumito Raher, Michael J. Morgan, John G. Coman, Tereza Lee, Candace Cuesta, Jose Maria Thibault, Helene Bloch, Kenneth D. Picard, Michael H. Scherrer-Crosbie, Marielle TI Myocardial Alterations in Senescent Mice and Effect of Exercise Training A Strain Rate Imaging Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE aging; echocardiography; exercise ID CARDIOVASCULAR-DISEASE ENTERPRISES; LEFT-VENTRICULAR CONTRACTILITY; PRESSURE-VOLUME RELATIONSHIPS; AGE-ASSOCIATED CHANGES; AGING HEART; IN-VIVO; ECHOCARDIOGRAPHIC-ASSESSMENT; DOPPLER-ECHOCARDIOGRAPHY; QUANTITATIVE ASSESSMENT; MAJOR SHAREHOLDERS AB Background-Aging is accompanied by an alteration in myocardial contractility. However, its noninvasive detection is difficult. The effect of chronic exercise on this decrease is unknown. Murine models of senescence are increasingly used to test therapies in aging. We tested whether strain rate imaging detected left ventricular (LV) systolic dysfunction in aging mice and was able to assess a potential improvement after exercise. Methods and Results-Young (3 weeks), adult (2 to 3 months), and old (6 to 18 months) C57BL6 male mice underwent echocardiograms with strain rate imaging, either in sedentary conditions or before, 2 weeks and 4 weeks after chronic swimming. Hemodynamic parameters of LV function including maximal and end-systolic elastance were obtained before euthanizing. LV fibrosis was measured using Sirius red staining. Conventional echocardiography was unable to detect LV systolic dysfunction in old mice, whereas both systolic strain rate and load-independent hemodynamic parameters such as preload recruitable stroke work and end-systolic elastance were significantly decreased. Both strain rate and load-independent hemodynamic parameters normalized after 4 weeks of exercise. Both endocardial and epicardial fibrosis were increased in the LV of aging mice. Endocardial fibrosis decreased in exercised aged mice. Conclusions-Strain rate noninvasively detects LV systolic dysfunction associated with aging in mice, whereas conventional echocardiography does not. Chronic exercise normalizes LV systolic function and decreases fibrosis in old mice. Strain rate imaging in mice may be a useful tool to monitor the effect of new therapeutic strategies preventing the myocardial dysfunction associated with aging. (Circ Cardiovasc Imaging. 2008;1:227-234.) C1 [Derumeaux, Genevieve; Thibault, Helene] Univ Lyon 1, Fac Med Lyon Nord, INSERM, U886, F-69373 Lyon 8, France. [Ichinose, Fumito; Raher, Michael J.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Derumeaux, Genevieve; Raher, Michael J.; Morgan, John G.; Coman, Tereza; Lee, Candace; Cuesta, Jose Maria; Picard, Michael H.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Raher, Michael J.; Bloch, Kenneth D.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Derumeaux, G (reprint author), Univ Lyon 1, Fac Med Lyon Nord, INSERM, U886, F-69373 Lyon 8, France. EM genevieve.derumeaux@chu-lyon.fr OI Picard, Michael/0000-0002-9264-3243 FU Scientist Development Grant; National Heart, Lung, and Blood Institute Public Health Service [HL-42397, HL-70896, HL-71987] FX This study was supported by a Scientist Development Grant (M.S.C.) as well as grants HL-42397, HL-70896, and HL-71987 from the National Heart, Lung, and Blood Institute Public Health Service (K. D. B.). NR 46 TC 18 Z9 20 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2008 VL 1 IS 3 BP 227 EP 234 DI 10.1161/CIRCIMAGING.107.745919 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 446NR UT WOS:000266128800009 PM 19808547 ER PT J AU Dinkel, J Bartling, SH Kuntz, J Grasruck, M Kopp-Schneider, A Iwasaki, M Dimmeler, S Gupta, R Semmler, W Kauczor, HU Kiessling, F AF Dinkel, Julien Bartling, Soenke H. Kuntz, Jan Grasruck, Michael Kopp-Schneider, Annette Iwasaki, Masayoshi Dimmeler, Stefanie Gupta, Rajiv Semmler, Wolfhard Kauczor, Hans-Ulrich Kiessling, Fabian TI Intrinsic Gating for Small-Animal Computed Tomography A Robust ECG-Less Paradigm for Deriving Cardiac Phase Information and Functional Imaging SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE flat-panel detector; imaging; intrinsic gating; small-animal imaging; tomography ID CINE MRI; MICE; CT; ECHOCARDIOGRAPHY; RECONSTRUCTION; PRINCIPLES; KYMOGRAM; ACCURATE; MOTION; MOUSE AB Background-A projection-based method of intrinsic cardiac gating in small-animal computed tomography imaging is presented. Methods and Results-In this method, which operates without external ECG monitoring, the gating reference signal is derived from the raw data of the computed tomography projections. After filtering, the derived gating reference signal is used to rearrange the projection images retrospectively into data sets representing different time points in the cardiac cycle during expiration. These time-stamped projection images are then used for tomographic reconstruction of different phases of the cardiac cycle. Intrinsic gating was evaluated in mice and rats and compared with extrinsic retrospective gating. An excellent agreement was achieved between ECG-derived gating signal and self-gating signal (coverage probability for a difference between the 2 measurements to be less than 5 ins was 89.2% in mice and 85.9% in rats). Functional parameters (ventricular volumes and ejection fraction) obtained from the intrinsic and the extrinsic data sets were not significantly different. The ease of use and reliability of intrinsic gating were demonstrated via a chemical stress test on 2 mice, in which the system performed flawlessly despite an increased heart rate. Because of intrinsic Gating, the image quality was improved to the extent that even the coronary arteries of mice could be Visualized in vivo despite a heart rate approaching 430 bpm. Feasibility of intrinsic gating for functional imaging and assessment of cardiac wall motion abnormalities was successfully tested in a mouse model of myocardial infarction. Conclusions-Our results demonstrate that self-gating using advanced software postprocessing of projection data promises to be a valuable tool for rodent computed tomography imaging and renders ECG gating with external electrodes superfluous. (Circ Cardiovasc Imaging. 2008;1:235-243.) C1 [Dinkel, Julien; Kauczor, Hans-Ulrich] German Canc Res Ctr, Dept Radiol, D-69120 Heidelberg, Germany. [Bartling, Soenke H.; Kuntz, Jan; Semmler, Wolfhard; Kiessling, Fabian] German Canc Res Ctr, Dept Med Phys Radiol, D-69120 Heidelberg, Germany. [Kopp-Schneider, Annette] German Canc Res Ctr, Dept Stat, D-69120 Heidelberg, Germany. [Grasruck, Michael] Siemens Med Solut, Forchheim, Germany. [Iwasaki, Masayoshi; Dimmeler, Stefanie] Univ Frankfurt, Dept Mol Cardiol, D-6000 Frankfurt, Germany. [Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kauczor, Hans-Ulrich] Univ Heidelberg Hosp, Dept Radiol, Heidelberg, Germany. [Kiessling, Fabian] Rhein Westfal TH Aachen, Dept Expt Mol Imaging, Aachen, Germany. RP Dinkel, J (reprint author), German Canc Res Ctr, Dept Radiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM j.dinkel@dkfz-heidelberg.de OI Kopp-Schneider, Annette/0000-0002-1810-0267 FU German Research Foundation FX This work was supported by the transregional grant "Vascular Differentiation and Remodeling" from the German Research Foundation (TR23, DFG). NR 29 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2008 VL 1 IS 3 BP 235 EP 243 DI 10.1161/CIRCIMAGING.108.784702 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 446NR UT WOS:000266128800010 PM 19808548 ER PT J AU Sinusas, AJ Bengel, F Nahrendorf, M Epstein, FH Wu, JC Villanueva, FS Fayad, ZA Gropler, RJ AF Sinusas, Albert J. Bengel, Frank Nahrendorf, Matthias Epstein, Frederick H. Wu, Joseph C. Villanueva, Flordeliza S. Fayad, Zahi A. Gropler, Robert J. TI Multimodality Cardiovascular Molecular Imaging, Part I SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE cardiovascular diseases; diagnosis; imaging; radionuclide imaging; image three-dimensional; molecular probes ID POSITRON-EMISSION-TOMOGRAPHY; OPTICAL COHERENCE TOMOGRAPHY; INTERCELLULAR-ADHESION MOLECULE-1; ULTRASOUND CONTRAST AGENTS; REPORTER GENE-EXPRESSION; SMALL-ANIMAL PET; INTRAVASCULAR ULTRASOUND; TIME-COURSE; IRON-OXIDE; MICROBUBBLES C1 [Sinusas, Albert J.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Bengel, Frank] Johns Hopkins Univ, Inst Med, Baltimore, MD USA. [Nahrendorf, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Epstein, Frederick H.] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. [Wu, Joseph C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Villanueva, Flordeliza S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Fayad, Zahi A.] Mt Sinai Sch Med, New York, NY USA. [Gropler, Robert J.] Washington Univ, Sch Med, St Louis, MO USA. RP Sinusas, AJ (reprint author), Yale Univ, Sch Med, 3FMP,POB 208017, New Haven, CT 06520 USA. EM albert.sinusas@yale.edu NR 96 TC 62 Z9 64 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2008 VL 1 IS 3 BP 244 EP 256 DI 10.1161/CIRCIMAGING.108.824359 PG 13 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 446NR UT WOS:000266128800011 PM 19808549 ER PT J AU Arnold, SV Morrow, DA Wang, KJ Lei, Y Mahoney, EM Scirica, BM Braunwald, E Cohen, DJ AF Arnold, Suzanne V. Morrow, David A. Wang, Kaijun Lei, Yang Mahoney, Elizabeth M. Scirica, Benjamin M. Braunwald, Eugene Cohen, David J. TI Effects of Ranolazine on Disease-Specific Health Status and Quality of Life Among Patients With Acute Coronary Syndromes Results from the MERLIN-TIMI 36 Randomized Trial SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE angina; quality of life; trials; ranolazine AB Background-Ranolazine has been shown to reduce myocardial ischemia and symptom severity among selected patients with chronic angina. However, data regarding the effect of ranolazine on health status/quality of life (QOL) are limited. Methods and Results-We performed a prospective QOL analysis alongside the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial, a randomized, double-blind, placebo-controlled trial of ranolazine in 6560 patients with non-ST-elevation acute coronary syndromes. Health status/QOL was evaluated at baseline and 4, 8, and 12 months after index hospitalization using the Seattle Angina Questionnaire, Rose dyspnea scale, SF-12, and EuroQol-5D. Health status/QOL scores improved significantly at all follow-up time points for both treatment arms. In the overall population, randomization to ranolazine was associated with minimal 12-month improvements in angina frequency and Seattle Angina Questionnaire-QOL (P<0.05). In subsequent exploratory analyses, there was a significant interaction between the benefits of ranolazine and anginal status before the index event. Among patients with prior angina (n=3565), treatment with ranolazine was associated with modest benefits across the full range of QOL domains, with the greatest benefits observed in angina frequency (mean effect=3.4; P<0.001) and Seattle Angina Questionnaire-QOL (mean effect=2.7; P<0.001). There were no significant benefits among patients without prior angina, however. Conclusion-Among a broad population of patients with unstable coronary disease, ranolazine had a minimal effect on disease-specific health status and QOL over approximate to 12 months of follow-up. Posthoc subgroup analysis, however, suggested a modest benefit among the subgroup of patients with angina before their acute coronary syndromes event. (Circ Cardiovasc Qual Outcomes. 2008;1:107-115.) C1 [Cohen, David J.] St Lukes Mid Amer Heart Inst, Div Cardiovasc, Kansas City, MO 64111 USA. [Morrow, David A.; Scirica, Benjamin M.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Cohen, DJ (reprint author), St Lukes Mid Amer Heart Inst, Div Cardiovasc, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM dcohen@saint-lukes.org FU CV Therapeutics FX The MERLIN-TIMI 36 Trial was funded by a grant from CV Therapeutics. NR 24 TC 25 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2008 VL 1 IS 2 BP 107 EP 115 DI 10.1161/CIRCOUTCOMES.108.798009 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V11AL UT WOS:000207504400007 PM 20031797 ER PT J AU Go, AS Magid, DJ Wells, B Sung, SH Cassidy-Bushrow, AE Greenlee, RT Langer, RD Lieu, TA Margolis, KL Masoudi, FA McNeal, CJ Murata, GH Newton, KM Novotny, R Reynolds, K Roblin, DW Smith, DH Vupputuri, S White, RE Olson, J Rumsfeld, JS Gurwitz, JH AF Go, Alan S. Magid, David J. Wells, Barbara Sung, Sue Hee Cassidy-Bushrow, Andrea E. Greenlee, Robert T. Langer, Robert D. Lieu, Tracy A. Margolis, Karen L. Masoudi, Frederick A. McNeal, Catherine J. Murata, Glen H. Newton, Katherine M. Novotny, Rachel Reynolds, Kristi Roblin, Douglas W. Smith, David H. Vupputuri, Suma White, Robert E. Olson, Jean Rumsfeld, John S. Gurwitz, Jerry H. TI The Cardiovascular Research Network A New Paradigm for Cardiovascular Quality and Outcomes Research SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cardiovascular disease; risk factors; outcomes; epidemiology; quality of care ID ACUTE MYOCARDIAL-INFARCTION; BARE-METAL STENTS; SIROLIMUS-ELUTING STENTS; ACUTE CORONARY SYNDROMES; CLINICAL-DATA STANDARDS; ASSOCIATION TASK-FORCE; HMO-RESEARCH-NETWORK; KEY DATA ELEMENTS; NATIONAL REGISTRY; HEART-FAILURE AB Background-A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes. Methods and Results-The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximate to 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators. Conclusions-The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases. (Circ Cardiovasc Qual Outcomes. 2008;1:138-147.) C1 [Go, Alan S.; Sung, Sue Hee] Univ Calif San Francisco, Kaiser Permanente No Calif, San Francisco, CA 94143 USA. [Magid, David J.] Univ Colorado, Kaiser Permanente Colorado, Denver, CO 80202 USA. [Wells, Barbara; Olson, Jean] NHLBI, Bethesda, MD 20892 USA. [Cassidy-Bushrow, Andrea E.] Henry Ford Hlth Syst, Detroit, MI USA. [Greenlee, Robert T.] Univ Wisconsin, Marshfield Clin Fdn Med Res & Educ, Madison, WI USA. [Langer, Robert D.] Geisinger Hlth Syst, Danville, PA USA. [Lieu, Tracy A.] Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. [Lieu, Tracy A.] Harvard Univ, Sch Med, Boston, MA USA. [Margolis, Karen L.] Univ Minnesota, HealthPartners Res Fdn, Minneapolis, MN USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [McNeal, Catherine J.] Scott & White Mem Hosp & Clin, Temple, TX USA. [McNeal, Catherine J.] Texas A&M Univ, Texas A&M Hlth Sci Ctr, College Stn, TX USA. [Murata, Glen H.; White, Robert E.] Univ New Mexico, Albuquerque, NM 87131 USA. [Murata, Glen H.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. [Newton, Katherine M.] Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. [Newton, Katherine M.; Smith, David H.] Univ Washington, Seattle, WA 98195 USA. [Novotny, Rachel] Univ Hawaii, Kaiser Permanente Ctr Hlth Res Hawaii, Honolulu, HI 96822 USA. [Reynolds, Kristi] Kaiser Permanente So Calif, Pasadena, CA USA. [Roblin, Douglas W.; Vupputuri, Suma] Kaiser Permanente Georgia, Atlanta, GA USA. [Roblin, Douglas W.] Emory Univ, Atlanta, GA 30322 USA. [Smith, David H.] Kaiser Permanente NW, Portland, OR USA. [Smith, David H.] Oregon State Univ, Corvallis, OR 97331 USA. [White, Robert E.] Lovelace Clin Fdn, Albuquerque, NM USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Gurwitz, Jerry H.] Meyers Primary Care Inst & Fallon Community Hlth, Worcester, MA USA. [Gurwitz, Jerry H.] Univ Massachusetts, Amherst, MA 01003 USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA. EM Alan.S.Go@kp.org OI Cassidy-Bushrow, Andrea/0000-0001-8272-4448 FU National Heart, Lung, and Blood Institute [U19 HL91179-01] FX This work was supported by National Heart, Lung, and Blood Institute cooperative agreement U19 HL91179-01. NR 44 TC 49 Z9 49 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2008 VL 1 IS 2 BP 138 EP 147 DI 10.1161/CIRCOUTCOMES.108.801654 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V11AL UT WOS:000207504400012 PM 20031802 ER PT J AU Semigran, MJ AF Semigran, Marc J. TI Phosphodiesterase Type 5 Inhibition A Support of the Left Ventricular Assist Device Bridge to Transplant SO CIRCULATION-HEART FAILURE LA English DT Editorial Material DE heart-assist device; heart failure; pulmonary heart disease; transplantation C1 [Semigran, Marc J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM msemigran@partners.org NR 1 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2008 VL 1 IS 4 BP 211 EP 212 DI 10.1161/CIRCHEARTFAILURE.108.830570 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446NJ UT WOS:000266128000001 PM 19808293 ER PT J AU Lewis, GD Shah, RV Pappagianopolas, PP Systrom, DM Semigran, MJ AF Lewis, Gregory D. Shah, Ravi V. Pappagianopolas, Paul P. Systrom, David M. Semigran, Marc J. TI Determinants of Ventilatory Efficiency in Heart Failure The Role of Right Ventricular Performance and Pulmonary Vascular Tone SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; exercise; ventilatory efficiency ID FUNCTIONAL-CAPACITY; EXERCISE CAPACITY; ARTERY PRESSURE; OXYGEN-UPTAKE; HIGH-RISK; SILDENAFIL; HYPERTENSION; HEMODYNAMICS; REFLEX; ERGOREFLEX AB Background-Ventilatory efficiency, right ventricular (RV) function, and secondary pulmonary hypertension are each prognostic indicators in patients with heart failure due to left ventricular systolic dysfunction, but the relationships among these variables have not been comprehensively investigated. In this study, we hypothesized that inefficient ventilation during exercise, as defined by an abnormally steep relationship between ventilation and carbon dioxide Output (VE/VCO(2) slope), may be a marker of secondary pulmonary hypertension and RV dysfunction in heart failure. Methods and Results-A cohort of patients with systolic heart failure (mean +/- SD age, 58 +/- 13years; left ventricular ejection fraction, 0.27 +/- 0.05; peak oxygen uptake, 11.2 +/- 3.2 mL kg(-1) min(-1)) underwent incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring and first-pass radionuclide ventriculography before and after 12 weeks of treatment with sildenafil, a selective pulmonary vasodilator, or placebo. VE/VCO(2) slope was positively related to rest and exercise pulmonary vascular resistance (R=0.39 and R=0.60, respectively) and rest pulmonary capillary wedge pressure (R=0.49, P<0.005 for all) and weakly indirectly related to peak exercise RV ejection fraction (R=-0.29, P=0.03). Over the 12-week study period, VE/VCO(2) slope fell 8 +/- 3% (P=0.02) with sildenafil and was unchanged with placebo. Changes in VE/VCO(2) Slope correlated with changes in exercise pulmonary vascular resistance (R=0.69, P<0.001) and rest and exercise RV ejection fraction (R=-0.58 and -0.40, respectively, both P<0.05). Conclusions-In patients with systolic heart failure and secondary pulmonary hypertension, ventilatory efficiency is closely related to RV function and pulmonary vascular tone during exercise. (Circ Heart Fail. 2008;1:227-233.) C1 [Lewis, Gregory D.; Semigran, Marc J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Shah, Ravi V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Pappagianopolas, Paul P.; Systrom, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Gray Bigelow 8,55 Fruit St, Boston, MA 02114 USA. EM glewis@partners.org OI Systrom, David/0000-0002-9610-6330 FU Heart Failure Society of America; American Heart Association Fellow-to-Faculty Award; Harvard/MIT Clinical Investigator Training Program in collaboration with Pfizer Inc and Merck Company Inc; National Heart Lung and Blood Institute [HL091106, HL04021] FX This work was supported by a grant from the Heart Failure Society of America (to G.D.L.). the American Heart Association Fellow-to-Faculty Award (to G.D.L.), the Harvard/MIT Clinical Investigator Training Program in collaboration with Pfizer Inc and Merck & Company Inc (to G.D.L.), and grant HL091106 (to G.D.L.) and grant HL04021 (to M.J.S.) from the National Heart Lung and Blood Institute. NR 31 TC 52 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2008 VL 1 IS 4 BP 227 EP 233 DI 10.1161/CIRCHEARTFAILURE.108.785501 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446NJ UT WOS:000266128000004 PM 19808296 ER PT J AU Notarangelo, LD Rucci, F Marrella, V Poliani, L Yan, C Sekiguchi, JA Caraffi, S Facchetti, F Alt, FW Villa, A AF Notarangelo, L. D. Rucci, F. Marrella, V Poliani, L. Yan, C. Sekiguchi, J. A. Caraffi, S. Facchetti, F. Alt, F. W. Villa, A. TI Hypomorphic V(D)J recombination mouse mutants have a different impact on thymic mechanisms of deletional and non-deletional central tolerance: implications for Omenn syndrome and leaky SCID SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 [Notarangelo, L. D.; Rucci, F.; Caraffi, S.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Marrella, V] IRCCS Humanitas, CNR ITB, Rozzano, Italy. [Poliani, L.; Facchetti, F.] Univ Brescia, Brescia, Italy. [Yan, C.; Alt, F. W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Sekiguchi, J. A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Villa, A.] San Raffaele TIGET, Rozzano, Italy. RI Poliani, Pietro Luigi/E-8145-2010; Notarangelo, Luigi/F-9718-2016; Facchetti, Fabio/E-7190-2010 OI Poliani, Pietro Luigi/0000-0002-5662-8978; Notarangelo, Luigi/0000-0002-8335-0262; Facchetti, Fabio/0000-0003-4975-2388 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 SU 1 BP 7 EP 7 PG 1 WC Immunology SC Immunology GA 398JD UT WOS:000262727500012 ER PT J AU Beadling, C Jacobson-Dunlop, E Hodi, FS Le, C Warrick, A Patterson, J Town, A Harlow, A Cruz, F Azar, S Rubin, BP Muller, S West, R Heinrich, MC Corless, CL AF Beadling, Carol Jacobson-Dunlop, Erick Hodi, F. Stephen Le, Claudia Warrick, Andrea Patterson, Janice Town, Ajia Harlow, Amy Cruz, Frank, III Azar, Sharl Rubin, Brian P. Muller, Susan West, Rob Heinrich, Michael C. Corless, Christopher L. TI KIT Gene Mutations and Copy Number in Melanoma Subtypes SO CLINICAL CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; EXON-15 BRAF MUTATIONS; C-KIT; MALIGNANT-MELANOMA; IMATINIB MESYLATE; METASTATIC MELANOMA; ACTIVATING MUTATIONS; CUTANEOUS MELANOMA; PROTEIN EXPRESSION; CD-117 EXPRESSION AB Purpose: We recently identified a KIT exon 11 mutation in an anorectal melanoma of a patient who had an excellent response to treatment with imatinib. To determine the frequency of KIT mutations across melanoma subtypes, we surveyed a large series of tumors. Experimental Design: One hundred eighty-nine melanomas were screened for mutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. A subset of cases was evaluated for BRAF and NRAS mutations. Immunohistochemistry was done to assess KIT (CD117) expression. Results: KIT mutations were detected in 23% (3 of 13) of acral melanomas, 15.6% (7 of 45) of mucosal melanomas, 7.7% (1 of 13) of conjunctival melanomas, 1.7% (1 of 58) of cutaneous melanomas, and 0% (0 of 60) of choroidal melanomas. Almost all the KIT mutations were of the type predicted to be imatinib sensitive. There was no overlap with NRAS mutations (11.1% of acral and 24.3% of mucosal tumors) or with BRAF mutations (absent in mucosal tumors). Increased KIT copy number was detected in 27.3% (3 of 11) of acral and 26.3% (10 of 38) of mucosal melanomas, but was less common among cutaneous (6.7%; 3 of 45), conjunctival (7.1%; 1 of 14), and choroidal melanomas (0 of 28). CD117 expression, present in 39% of 105 tumors representing all melanoma types, did not correlate with either KIT mutation status or KIT copy number. Conclusions: Our findings confirm that KIT mutations are most common in acral and mucosal melanomas but do not necessarily correlate with KIT copy number or CD117 expression. Screening for KIT mutations may open up new treatment options for melanoma patients. C1 [Cruz, Frank, III; Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Beadling, Carol; Jacobson-Dunlop, Erick; Le, Claudia; Warrick, Andrea; Patterson, Janice; Town, Ajia; Harlow, Amy; Azar, Sharl; Heinrich, Michael C.; Corless, Christopher L.] Oregon Hlth & Sci Univ, Oregon Canc Inst, Portland, OR 97239 USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Div Hematol & Oncol, Portland, OR 97239 USA. [Heinrich, Michael C.] VA Med Ctr, Portland, OR USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rubin, Brian P.] Cleveland Clin, Dept Pathol, Cleveland, OH 44106 USA. [Muller, Susan] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [West, Rob] VA Med Ctr, Dept Pathol, Palo Alto, CA USA. RP Corless, CL (reprint author), Oregon Hlth & Sci Univ, Dept Pathol, Mailcode L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM corlessc@ohsu.edu OI Patterson, Janice/0000-0002-8969-2933 NR 45 TC 265 Z9 269 U1 1 U2 8 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 NOV 1 PY 2008 VL 14 IS 21 BP 6821 EP 6828 DI 10.1158/1078-0432.CCR-08-0575 PG 8 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200015 PM 18980976 ER PT J AU Chin, TM Quinlan, MP Singh, A Sequist, LV Lynch, TJ Haber, DA Sharma, SV Settleman, J AF Chin, Tan Min Quinlan, Margaret P. Singh, Anurag Sequist, Lecia V. Lynch, Thomas J. Haber, Daniel A. Sharma, Sreenath V. Settleman, Jeffrey TI Reduced Erlotinib Sensitivity of Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer following Cisplatin Exposure: A Cell Culture Model of Second-line Erlotinib Treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; ACQUIRED-RESISTANCE; EGFR MUTATIONS; GENE-MUTATIONS; GEFITINIB; PTEN; THERAPY; KINASE; EXPRESSION; PATHWAY AB Purpose: Epidermal growth factor receptor (EGFR) kinase inhibitors induce dramatic clinical responses in a subset of non-small cell lung cancer (NSCLC) patients with advanced disease, and such responses are correlated with the presence of somatic activating mutations within the EGFR kinase domain. Consequently, one of these inhibitors, erlotinib, has been Food and Drug Administration-approved as a second-or third-line treatment for chemotherapy-refractory advanced NSCLC. However, responses are typically relatively short-lived due to acquired drug resistance, prompting studies to determine whether first-line treatment with EGFR inhibitors could provide greater clinical benefit. NSCLC-derived cell lines have provided a powerful system for modeling EGFR mutation-correlated sensitivity to EGFR inhibitors and for modeling mechanisms of acquired drug resistance that are observed clinically. Experimental Design: In a cell culture model of an erlotinib-sensitive EGFR-mutant NSCLC cell line, we tested the hypothesis that prior exposure to platinum agents, a standard component of NSCLC chemotherapy treatment, affects the subsequent response to erlotinib. Results: Indeed, NSCLC cells initially selected for growth in cisplatin exhibit 5-fold reduced sensitivity to erlotinib, even after propagating the cisplatin-treated cells in the absence of cisplatin for several months. This lingering effect of cisplatin exposure appears to reflect changes in PTEN tumor suppressor activity and persistent EGFR-independent signaling through the phosphatidylinositol 3-kinase/AKTsurvival pathway. Conclusions: These preclinical findings suggest that first-line chemotherapy treatment of EGFR-mutant NSCLCs may reduce the benefit of subsequent treatment with EGFR kinase inhibitors and should prompt further clinical investigation of these inhibitors as a first-line therapy in NSCLC. C1 [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM Settleman@helix.mgh.harvard.edu RI Singh, Anurag/C-7347-2014 OI Singh, Anurag/0000-0003-4705-8683 FU NIH [R01 CA115830]; V Foundation FX NIH grant R01 CA115830 and V Foundation for Cancer Research award (J. Settleman).; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 35 TC 31 Z9 32 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2008 VL 14 IS 21 BP 6867 EP 6876 DI 10.1158/1078-0432.CCR-08-0093 PG 10 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200020 PM 18980981 ER PT J AU Song, WH van der Vliet, HJJ Tai, YT Prabhala, R Wang, RJ Podar, K Catley, L Shammas, MA Anderson, KC Balk, SP Exley, MA Munshi, NC AF Song, Weihua van der Vliet, Hans J. J. Tai, Yu-Tzu Prabhala, Rao Wang, Ruojie Podar, Klaus Catley, Laurence Shammas, Masood A. Anderson, Kenneth C. Balk, Steven P. Exley, Mark A. Munshi, Nikhil C. TI Generation of Antitumor Invariant Natural Killer T Cell Lines in Multiple Myeloma and Promotion of Their Functions via Lenalidomide: A Strategy for Immunotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; CANCER-PATIENTS; ANTIGEN PRESENTATION; INTERFERON-GAMMA; DENDRITIC CELLS; IFN-GAMMA; CYTOTOXICITY; CD1D; PROLIFERATION AB Purpose: CD1d-restricted invariant natural killer T (iNKT) cells are important immunoregulatory cells in antitumor immune responses. However, the quantitative and qualitative defects of iNKT cells in advanced multiple myeloma hamper their antitumor effects. Therefore, the development of functional iNKT cells may provide a novel strategy for the immunotherapy in multiple myeloma. Experimental Design: We activated and expanded iNKT cells from multiple myeloma patients with alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells, characterized their antitumor effects by the cytokine production profile and cytotoxicity against multiple myeloma cells, and explored the effects of immunomodulatory drug lenalidomide on these iNKT cells. We also investigated the expression of CD1d by primary multiple myeloma cells and its function to activate iNKT cells. Results: We established highly purified functional iNKT cell lines from newly diagnosed and advanced multiple myeloma patients. These CD1d-restricted iNKT cell lines produced high level of antitumor Th1 cytokine in response to a-GalCer-pulsed primary multiple myeloma cells, CD1d-transfected MM1S cell line, and dendritic cells. Moreover, iNKT cell lines displayed strong cytotoxicity against alpha-GalCer-pulsed primary multiple myeloma cells. Importantly, lenalidomide further augmented the Th1 polarization by iNKT cell lines via increased Th1 cytokine production and reduced Th2 cytokine production. We also showed that CD1d was expressed in primary multiple myeloma cells at mRNA and protein levels from the majority of multiple myeloma patients, but not in normal plasma cells and multiple myeloma cell lines, and CD1d(+) primary multiple myeloma cells presented antigens to activate iNKT cell lines. Conclusions: Taken together, our results provide the preclinical evidence for the iNKT cell-mediated immunotherapy and a rationale for their use in combination with lenalidomide in multiple myeloma treatment. C1 [Song, Weihua; Tai, Yu-Tzu; Prabhala, Rao; Podar, Klaus; Catley, Laurence; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [van der Vliet, Hans J. J.; Wang, Ruojie; Balk, Steven P.; Exley, Mark A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Hematol Oncol Div,Canc Biol Program, Boston, MA 02215 USA. [Prabhala, Rao; Shammas, Masood A.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Vet Adm Boston Hth Care Syst, W Roxbury, MA USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St,M1B28, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI van der Vliet, Hans/B-1176-2013; Catley, Laurence/E-5313-2013 FU NIH [P050-1007, PO1-7837807, RO1-OA124929, R01066917]; Research Service Veterans Health Care Merit Review Award FX NIH grants P050-100707 and PO1-78378 (K.C. Anderson and N-C. Munshi) and NIH grant RO1-OA124929 (N.C. Munshi) and Research Service Veterans Health Care Merit Review Award (N.C. Munshi) and NIH grant R01066917 (M.A. Exley). N.C. Munshi is a Leukemia Society Scholar in Translational Research. NR 28 TC 35 Z9 35 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 NOV 1 PY 2008 VL 14 IS 21 BP 6955 EP 6962 DI 10.1158/1078-0432.CCR-07-5290 PG 8 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200029 PM 18980990 ER PT J AU Yonesaka, K Zejnullahu, K Lindeman, N Homes, AJ Jackman, DM Zhao, F Rogers, AM Johnson, BE Janne, PA AF Yonesaka, Kimio Zejnullahu, Kreshnik Lindeman, Neal Homes, Alison J. Jackman, David M. Zhao, Feng Rogers, Andrew M. Johnson, Bruce E. Jaenne, Pasi A. TI Autocrine Production of Amphiregulin Predicts Sensitivity to Both Gefitinib and Cetuximab in EGFR Wild-type Cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL-LUNG-CANCER; PHASE-II TRIAL; REFRACTORY COLORECTAL-CANCER; CHEMOTHERAPY-NAIVE PATIENTS; GENE COPY NUMBER; TARGETED THERAPIES; TYROSINE KINASE; DISEASE-CONTROL; POOR-PROGNOSIS AB Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, lead to significant tumor regressions in 10% to 15% of non-small cell lung cancer (NSCLC) patients with EGFR activating mutations. However, 30% to 40% of NSCLC patients, majority of whom are EGFR wild-type, develop stable disease following EGFR tyrosine kinase inhibitor therapy. EGFR-directed antibodies (cetuximab) are effective treatments for head and neck squamous cell carcinomas, which seldom contain EGFR mutations. The determinant(s) of efficacy of EGFR-targeted therapies in EGFR wild-type cancers is not well defined. Experimental Design: We examined the relationship of EGFR ligands, EGF, transforming growth factor-alpha, and amphiregulin and the efficacy of gefitinib and cetuximab in EGFR wild-type NSCLC (n = 10) and head and neck squamous cell carcinoma (n = 4) cell lines. We compared amphiregulin expression using immunohistochemistry in EGFR wild-type NSCLC patients (n = 24) that developed either stable or progressive disease following erlotinib or gefitinib treatment. Results: Cell lines which produced >= 20 pmol/L amphiregulin, as detected by an ELISA, were significantly more likely to be growth inhibited by both gefitinib and cetuximab than those that produced minimal or no amphiregulin. In these cell lines, both cetuximab and gefitinib led to cell cycle arrest at the G(1)-S boundary and was associated with preferential inhibition of extracellular signal-regulated kinase 1/2 but not Akt signaling. Amphiregulin expression was significantly higher in NSCLC patients that developed stable disease compared with those that developed disease progression following gefitinib or erlotinib treatment. Conclusions: Amphiregulin expression may help select EGFR wild-type patients who are likely to develop stable disease from EGFR-targeted therapies. C1 [Yonesaka, Kimio; Zejnullahu, Kreshnik; Homes, Alison J.; Jackman, David M.; Zhao, Feng; Johnson, Bruce E.; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Yonesaka, Kimio; Zejnullahu, Kreshnik; Homes, Alison J.; Jackman, David M.; Zhao, Feng; Rogers, Andrew M.; Johnson, Bruce E.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lindeman, Neal] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Johnson, Bruce E.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Johnson, Bruce E.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org FU NIH [1RO1CA114465-01]; American Cancer Society [RSG-06-102-01-CCE]; National Cancer Institute Lung SPORE [P20CA90578-02]; Department of Defense [W81XWH06-1-0303]; Hazel and Samuel Bellin FX NIH grant 1RO1CA114465-01 (B.E. Johnson and P.A. Janne), American Cancer Society grant RSG-06-102-01-CCE (P.A. Janne), National Cancer Institute Lung SPORE grant P20CA90578-02 (B.Y.Y. and B.E. Johnson), Department of Defense grant W81XWH06-1-0303 (B.E. Johnson and P.A. Janne), and Hazel and Samuel Bellin research fund (P.A. Janne). NR 54 TC 79 Z9 81 U1 2 U2 8 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 NOV 1 PY 2008 VL 14 IS 21 BP 6963 EP 6973 DI 10.1158/1078-0432.CCR-08-0957 PG 11 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200030 PM 18980991 ER PT J AU Costa, DB Nguyen, KSH Cho, YC Sequist, LV Jackman, DM Riely, G Yeap, BY Halmos, B Kim, JH Janne, PA Huberman, MS Pao, W Tenen, DG Kobayashi, S AF Costa, Daniel B. Nguyen, Kim-Son H. Cho, Young C. Sequist, Lecia V. Jackman, David M. Riely, GregoryJ. Yeap, Beow Y. Halmos, Balazs Kim, Joo H. Jaenne, Pasi A. Huberman, Mark S. Pao, William Tenen, Daniel G. Kobayashi, Susumu TI Effects of Erlotinib in EGFR Mutated Non-Small Cell Lung Cancers with Resistance to Gefitinib SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOID-LEUKEMIA; PHASE-II TRIAL; ACQUIRED-RESISTANCE; PROLONGED SURVIVAL; T790M MUTATIONS; SUPPORTIVE CARE; GENE-MUTATIONS AB Purpose: Most lung cancers with activating epidermal growth factor receptor (EGFR) mutations respond to gefitinib; however, resistance to this tyrosine kinase inhibitor (TKI) invariably ensues. The T790M mutation occurs in 50% and MET amplification in 20% of TKI-resistant tumors. Other secondary mutations (D761Y and L747S) are rare. Our goal was to determine the effects of erlotinib 150 mg/d in EGFR mutated patients resistant to gefitinib 250 mg/d, because the EGFR TKI erlotinib is given at a higher biologically active dose than gefitinib. Experimental Design: Retrospective review of 18 EGFR mutated (exon 19 deletions, L858R, and L861Q) patients that were given gefitinib and subsequently erlotinib. Seven patients had tumor resampling after TKI therapy and were analyzed for secondary EGFR mutations and MET amplification. Results: Most patients (14 of 18) responded to gefitinib with median progression-free survival of 11 months (95% confidence interval, 4-16). After gefitinib resistance (de novo or acquired), 78% (14 of 18) of these patients displayed progressive disease while on erlotinib with progression-free survival of 2 months (95% confidence interval, 2-3). Six of 7 resampled patients acquired the T790M mutation, and 0 of 3 had MET amplification. Only 1 gefitinib-resistant patient with the acquired L858R-L747S EGFR, which in vitro is sensitive to achievable serum concentrations of erlotinib 150 mg/d, achieved a partial response to erlotinib. Conclusions: In EGFR mutated tumors resistant to gefitinib 250 mg/d, a switch to erlotinib 150 mg/d does not lead to responses in most patients. These findings are consistent with preclinical models, because the common mechanisms of TKI resistance (T790M and MET amplification) in vitro are not inhibited by clinically achievable doses of gefitinib or erlotinib. Alternative strategies to overcome TKI resistance must be evaluated. C1 [Costa, Daniel B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Sequist, Lecia V.; Yeap, Beow Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Jackman, David M.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Cho, Young C.; Kim, Joo H.] Yonsei Univ, Coll Med, Seoul, South Korea. [Riely, GregoryJ.; Pao, William] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Halmos, Balazs] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Costa, DB (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM dbcosta@bidmc.harvard.edu OI Costa, Daniel/0000-0002-0689-395X; Tenen, Daniel/0000-0002-6423-3888 FU NIH [K99CA126026]; Specialized Program of Research Excellence in Lung Cancer [2PA50-CA09057806]; American Society of Clinical Oncology Young Investigator Award; AACR-AstraZeneca-Cancer Research and Prevention Foundation; Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology; OSI-Pharmaceuticals or Genentech FX NIH grants K99CA126026 (S. Kobayashi) and Specialized Program of Research Excellence in Lung Cancer 2PA50-CA09057806 (D.B. Costa, B. Halmos, D.G. Tenen); American Society of Clinical Oncology Young Investigator Award (D.B. Costa), AACR-AstraZeneca-Cancer Research and Prevention Foundation Fellowship in Translational Lung Cancer Research (D.B. Costa); Clinical Investigator Training Program from Beth Israel Deaconess Medical Center-Harvard/MIT Health Sciences and Technology in collaboration with Pfizer and Merck & Co. (D.B. Costa); and research funding by OSI-Pharmaceuticals or Genentech (B. Halmos, P.A. Janne, and L.V. Sequist). NR 65 TC 95 Z9 104 U1 0 U2 7 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 NOV 1 PY 2008 VL 14 IS 21 BP 7060 EP 7067 DI 10.1158/1078-0432.CCR-08-1455 PG 8 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200042 PM 18981003 ER PT J AU Yachimski, P Nishioka, NS Richards, E Hur, C AF Yachimski, Patrick Nishioka, Norman S. Richards, Ethan Hur, Chin TI Treatment of Barrett's Esophagus With High-Grade Dysplasia or Cancer: Predictors of Surgical Versus Endoscopic Therapy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID LONG-TERM SURVIVAL; QUALITY-OF-LIFE; PHOTODYNAMIC THERAPY; UNITED-STATES; PRACTICE PATTERNS; ADENOCARCINOMA; ESOPHAGECTOMY; MANAGEMENT; RESECTION; MORTALITY AB Background & Aims: Patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma are at risk of progression to invasive carcinoma. Both esophagectomy and endoscopic ablation are treatment options. The aim of this study was to identify predictors of surgical versus endoscopic therapy at a tertiary center. Methods: An institutional database identified patients with Barrett's esophagus between 2003 and 2007. Demographic data and International Classification of Diseases-9th revision codes for esophagectomy, endoscopic ablation, as well as selected medical comorbidities were retrieved. Individual endoscopy, surgical, and pathology reports were reviewed. Results: Among 2107 individuals with Barrett's esophagus, 79 underwent esophagectomy and 80 underwent endoscopic ablation. The mean age was 63.1 +/- 10.6 years in the surgical group and 69.7 +/- 9.4 years in the ablation group (P < .0001). Among high-grade dysplasia/intramucosal carcinoma patients, 9 of 76 (12%) first seen by a gastroenterologist underwent esophagectomy, whereas 18 of 21 (86%) first seen by a surgeon underwent esophagectomy. In a logistic regression model, factors associated independently with esophagectomy were as follows: patient age of 60 or younger (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.65-14.9), cancer stage T1sm or greater (OR, 16.0; 95% CI, 5.60-45.6), and initial consultation performed by a surgeon (vs gastroenterologist) (OR, 35.1; 95% CI, 9.58-129). Conclusions: Patient age and cancer stage predict treatment modality for Barrett's esophagus with neoplasia. Treatment choice is influenced further by whether the initial evaluation is performed by a gastroenterologist or a surgeon. C1 [Yachimski, Patrick; Nishioka, Norman S.; Richards, Ethan; Hur, Chin] Harvard Univ, Gastrointestinal Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yachimski, Patrick; Nishioka, Norman S.] Harvard Univ, Wellman Ctr Photomed, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richards, Ethan; Hur, Chin] Harvard Univ, Inst Technol Assessment, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yachimski, P (reprint author), Harvard Univ, Gastrointestinal Unit, Sch Med, Massachusetts Gen Hosp, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM pyachimski@partners.org OI Hur, Chin/0000-0002-2819-7576 FU NIH [DK007191, K07CA107060] FX P.Y. and N.S.N. have received consulting honoraria from Axcan Scandipharm. P.Y. was supported by NIH T32 training grant DK007191. C.H. was supported by NIH grant K07CA107060. NR 32 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2008 VL 6 IS 11 BP 1206 EP 1211 DI 10.1016/j.cgh.2008.04.031 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 376VK UT WOS:000261210900012 PM 18619919 ER PT J AU Brunelli, SM Lynch, KE Ankers, ED Joffe, MM Yang, W Thadhani, RI Feldman, HI AF Brunelli, Steven M. Lynch, Katherine E. Ankers, Elizabeth D. Joffe, Marshall M. Yang, Wei Thadhani, Ravi I. Feldman, Harold I. TI Association of Hemoglobin Variability and Mortality among Contemporary Incident Hemodialysis Patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; QUALITY-OF-LIFE; ANEMIA MANAGEMENT; CARDIOVASCULAR MORBIDITY; LEVEL VARIABILITY; HEMATOCRIT AB Background and objectives: Evidence exists that variability in hemoglobin may be an independent risk factor for mortality among hemodialysis patients. These observations were based on a 1996 cohort, a time when anemia management differed greatly from present. Design, settings, participants and measurements: A retrospective cohort study of patients incident to Fresenius Medical Care units between 2004 and 2005 (n = 6644). Hemoglobin variability (Hgb-Var) was defined for each subject as the residual SD of a linear regression model of time on hemoglobin. Results: The mean (SD) of Hgb-Var was 1.13 (0.55) g/dl. In the primary analysis, each g/dl increase of Hgb-Var was associated with an adjusted hazard ratio (95% confidence interval) for all-cause mortality of 1.11 (0.92 to 1.33). No significant interaction with Hgb-Var and mortality was found on the basis of age (P = 0.22), arterial disease (P = 0.45), Hgb slope (P = 0.68), or mean Hgb (P = 0.78). When Hgb-Var was defined by a regression model that included a quadratic term for time (enabling descriptions of curvilinear hemoglobin trajectories), model fit was greatly improved (P for difference <0.001). The corresponding adjusted hazard ratio (95% confidence interval) for all-cause mortality was 1.17 (0.93 to 1.49). Conclusions: Hgb-Var was not found to be associated with all-cause mortality when examined in a contemporary incident hemodialysis population. More research is needed to determine whether differences in these findings compared with prior analyses relate to temporal trends in anemia management or from differences in the relationship between Hgb-Var and outcomes among incident versus prevalent hemodialysis patients. C1 [Brunelli, Steven M.; Joffe, Marshall M.; Yang, Wei; Feldman, Harold I.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Brunelli, Steven M.; Lynch, Katherine E.; Feldman, Harold I.] Univ Penn, Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Ankers, Elizabeth D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA USA. RP Brunelli, SM (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. EM steven.brunelli@uphs.upenn.edu RI Yang, Wei/A-9223-2009 OI Yang, Wei/0000-0001-8984-4389 FU American Heart Association Fellow-to-Faculty Transition [0775021N]; Hoffman-LaRoche Company FX S.M.B. was supported by the American Heart Association Fellow-to-Faculty Transition Award 0775021N. Prior work on the 1996 cohort was supported by an unrestricted grant from Hoffman-LaRoche Company. NR 22 TC 22 Z9 23 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 NOV PY 2008 VL 3 IS 6 BP 1733 EP 1740 DI 10.2215/CJN.02390508 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 366TE UT WOS:000260505500022 PM 18922985 ER PT J AU Spiegel, BMR Melmed, G Robbins, S Esrailiant, E AF Spiegel, Breman M. R. Melmed, Gil Robbins, Sean Esrailiant, Eric TI Biomarkers and Health-Related Quality of Life in End-Stage Renal Disease: A Systematic Review SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID CHRONIC KIDNEY-DISEASE; INCIDENT HEMODIALYSIS-PATIENTS; PERITONEAL-DIALYSIS PATIENTS; PRACTICE PATTERNS; ANEMIA MANAGEMENT; PHYSICAL-ACTIVITY; EMPLOYMENT STATUS; MENTAL-HEALTH; MORTALITY; OUTCOMES AB Background and objectives: Health-related quality of life (HRQOL) predicts mortality in ESRD, yet adoption of HRQOL monitoring is not widespread, and regulatory authorities remain predominantly concerned with monitoring traditional biologic parameters. To assist with future efforts to adopt HRQOL monitoring while acknowledging the importance of biomarkers, this study sought to establish which domains of HRQOL are most affected by ESRD and to measure the strength of evidence linking common biomarkers to HRQOL in ESRD. Design, setting, participants, & measurements: A systematic review was performed to identify studies that measured HRQOL in ESRD. Data were abstracted according to a conceptual model regarding the measurement of HRQOL differences, and HRQOL data were converted to weighted mean effect sizes and correlation coefficients. Results: The impact of ESRD was largest in the Short Form 36 domains of physical functioning (e.g., role-physical, vitality) and smallest in mental functioning (e.g., mental health, role-emotional). Dialysis adequacy, as measured by Kt/V, was a poor correlate for Short Form 36 scores. Similarly, mineral metabolism (e.g., calcium X phosphorous, parathyroid hormone) and inflammatory (e.g., C-reactive protein, TNF) biomarkers had small effect sizes and correlations with HRQOL. In contrast, hematocrit demonstrated small to moderate relationships with mental and physical HRQOL, and nutritional biomarkers (e.g., albumin, creatinine, body mass index) demonstrated moderate to large relationships. Conclusions: HRQOL in ESRD is most affected in the physical domains, and nutritional biomarkers are most closely associated with these domains. In contrast, Kt/V, mineral metabolism indices, and inflammatory markers are poor HRQOL correlates. C1 [Spiegel, Breman M. R.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med,VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA 90073 USA. [Melmed, Gil; Esrailiant, Eric] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90073 USA. [Robbins, Sean] Amgen Inc, Global Hlth Econ, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med,VA Ctr Outcomes Res & Educ CORE, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU VA HSR&D Research Career Development [RCD 03 to 179-2]; CURE Research Center [NIH 2P30 DK 041301-17] FX B.M.R.S. is Supported by VA HSR&D Research Career Development Award RCD 03 to 179-2 and by the CURE Research Center (NIH 2P30 DK 041301-17). Additional support for this study was provided by an investigator-initiated research grant from Amgen, Inc. NR 88 TC 51 Z9 54 U1 0 U2 7 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 NOV PY 2008 VL 3 IS 6 BP 1759 EP 1768 DI 10.2215/CJN.00820208 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 366TE UT WOS:000260505500025 PM 18832106 ER PT J AU Young, JA Hwang, SJ Sarnak, MJ Hoffmann, U Massaro, JM Levy, D Benjamin, EJ Larson, MG Vasan, RS O'Donnell, CJ Fox, CS AF Young, Jill A. Hwang, Shih-Jen Sarnak, Mark J. Hoffmann, Udo Massaro, Joseph M. Levy, Daniel Benjamin, Emelia J. Larson, Martin G. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Association of Visceral and Subcutaneous Adiposity with Kidney Function SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SERUM CYSTATIN-C; IMPAIRED GLUCOSE-TOLERANCE; GLOMERULAR-FILTRATION-RATE; BODY-FAT DISTRIBUTION; METABOLIC SYNDROME; TISSUE VOLUMES; RENAL-FUNCTION; UNITED-STATES; RISK-FACTORS; MASS INDEX AB Background and objectives: Obesity is a risk factor for incident chronic kidney disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations. Design, setting, participants, & measurements: Participants from the Framingham Offspring Study who underwent abdominal computed tomography for VAT and SAT quantification were included (n = 1299; 53% women; mean age 60 yr). CKD was defined as estimated GFR < 60 ml/min per 1.73 m(2), as estimated using creatinine (n = 89) in the Modification of Diet ill Renal Disease (MDRD) formula or by cystatin C (n = 136). Regression models evaluated the cross-sectional relations between VAT and SAT with CKD and cystatin C, with age and gender adjustment and cardiovascular risk factor adjustment. Results: Neither VAT nor SAT was associated with CKD as estimated by the MDRD equation. In contrast, both VAT and SAT were associated with CKD when defined using cystatin-based equations. The estimated decrease in estimated GFR by cystatin C per 1-SD increase of VAT was 1.9 ml/min per 1.73 m(2) and for SAT was 2.6 ml/min per 1.73 m2 in a multivariable-adjusted model. Conclusions: VAT and SAT were associated with CKD when defined using cystatin C estimating equations but not when using a creatinine-based estimating equation. Mechanisms linking adipose tissue to cystatin C warrant further research. C1 [Young, Jill A.; Sarnak, Mark J.] Tufts Univ New England Med Ctr, Boston, MA USA. [Hoffmann, Udo; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffmann, Udo; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Hwang, Shih-Jen; Massaro, Joseph M.; Levy, Daniel; Benjamin, Emelia J.; Larson, Martin G.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [Hwang, Shih-Jen; Levy, Daniel; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute/National Institutes of Health [N01-HC-25195, 2K24HL04334] FX This study was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195). R.S.V. is supported in part by 2K24HL04334 (National Heart, Lung, and Blood Institute/National Institutes of Health). NR 37 TC 23 Z9 23 U1 0 U2 0 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 NOV PY 2008 VL 3 IS 6 BP 1786 EP 1791 DI 10.2215/CJN.02490508 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 366TE UT WOS:000260505500028 PM 18815239 ER PT J AU Watnick, S AF Watnick, Suzanne TI Academic Etiquette for the Nephrologist SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PHYSICIANS; UNAWARE AB Academic etiquette is an underexplored and underemphasized topic. Yet, a collegial atmosphere is essential to accomplish the missions of an academic medical center. Appropriate social, personal, and cultural behaviors are not only desirable, but they are also necessary to practice and emulate. As faculty in an academic center, one may want to share these thoughts with peers, students, and other healthcare providers. As a trainee, one may want dedicated lectures on this topic and to observe the behaviors modeled by mentors. This article attempts to outline principles of appropriate etiquette in the academic workplace. These include issues of loyalty, collegiality, and collaboration in daily activities from research to clinical care. Approaching personal interactions with grace and integrity can be ail essential tool in the pursuit of academic excellence and success. C1 Portland VA Med Ctr, Portland, OR 97239 USA. RP Watnick, S (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,P3NEPH, Portland, OR 97239 USA. EM watnicks@ohsu.edu NR 11 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 2008 VL 3 IS 6 BP 1884 EP 1886 DI 10.2215/CJN.01750408 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 366TE UT WOS:000260505500043 PM 18715991 ER PT J AU Vranceanu, AM Safren, S Zhao, MJ Cowan, J Ring, D AF Vranceanu, Ana-Maria Safren, Steven Zhao, Meijuan Cowan, James Ring, David TI Disability and Psychologic Distress in Patients with Nonspecific and Specific Arm Pain SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SELF-RATING SCALE; BACK-PAIN; SOMATIZATION; DEPRESSION; HYPOCHONDRIASIS; ARTHRITIS; SYMPTOMS; SHOULDER; ILLNESS AB Psychological illness influences the experience and expression of pain and disability. We tested three null hypotheses: (1) patients with nonspecific pain (medically unexplained and idiopathic) and patients with specific pain (discrete and verifiable) are equally likely to screen for psychiatric illnesses based on a validated screening questionnaire; (2) the presence of psychiatric illness (from a screening questionnaire) will not predict whether patients have specific or nonspecific pain type; and (3) across all patients and regardless of whether they have specific or nonspecific pain, psychiatric illness will not predict disability as measured by the Disabilities of the Arm Shoulder and Hand (DASH) questionnaire. We rejected all null hypotheses. The 41 patients with nonspecific arm pain were more likely than the 40 patients with specific arm pain to screen for a somatoform disorder (34% versus 7.5%), posttraumatic stress disorder (24% versus 7.5%), and panic disorder (12.2% versus 5%). The presence of anxiety and somatoform disorders predicted pain type (nonspecific versus specific) and arm-specific disability (DASH). Somatoform disorder was the strongest predictor of pain type and DASH scores. Based on a screening questionnaire, a comorbid psychiatric illness, a somatoform disorder in particular, is associated with nonspecific arm pain and arm-specific disability. C1 [Vranceanu, Ana-Maria; Zhao, Meijuan; Cowan, James; Ring, David] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthoped Surg, Boston, MA 02114 USA. [Vranceanu, Ana-Maria; Safren, Steven; Zhao, Meijuan; Cowan, James; Ring, David] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vranceanu, Ana-Maria; Safren, Steven] Massachusetts Gen Hosp, Behav Med Serv, Dept Psychiat, Boston, MA 02114 USA. [Zhao, Meijuan] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthoped Surg, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU AO Foundation; Small Bone Innovations; Wright Medical; Smith and Nephew FX One or more of the authors received funding from the AO Foundation (DR), Small Bone Innovations (DR), Wright Medical (DR), and Smith and Nephew (DR).; Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. NR 36 TC 23 Z9 24 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2008 VL 466 IS 11 BP 2820 EP 2826 DI 10.1007/s11999-008-0378-1 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 358HZ UT WOS:000259909000039 PM 18636306 ER PT J AU Smetana, GW Conde, MV AF Smetana, Gerald W. Conde, Michelle V. TI Preoperative Pulmonary Update SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Preoperative care; Intraoperative care; Intraoperative complications; Postoperative complications; Pulmonary; Respiratory; Perioperative complications; Elderly; Management ID RANDOMIZED CLINICAL-TRIAL; OBSTRUCTIVE SLEEP-APNEA; PERIOPERATIVE CARDIOVASCULAR EVALUATION; MAJOR NONCARDIAC SURGERY; COLLEGE-OF-PHYSICIANS; POSTOPERATIVE RESPIRATORY-FAILURE; PRACTICE GUIDELINES COMMITTEE; MULTIFACTORIAL RISK INDEX; ASSOCIATION TASK-FORCE; PATIENTS AGED 80 AB Postoperative pulmonary complications are an important source of surgical morbidity. In this paper, the authors review recent studies that shed light on emerging risk factors, a multifactorial index for respiratory failure, and the value of specific risk reduction strategies. Novel risk factors include advanced age, congestive heart failure, pulmonary hypertension, and obstructive sleep apnea. Important risk reduction strategies include postoperative lung expansion maneuvers, the selective use of nasogastric tubes, epidural analgesia, and inspiratory muscle training. C1 [Smetana, Gerald W.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Conde, Michelle V.] Univ Texas Hlth Sci Ctr San Antonio, Div Gen Med, San Antonio, TX 78229 USA. [Conde, Michelle V.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Smetana, GW (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave, Boston, MA 02215 USA. EM gsmetana@bidmc.harvard.edu NR 75 TC 7 Z9 7 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 2008 VL 24 IS 4 BP 607 EP + DI 10.1016/j.cger.2008.06.004 PG 19 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 375YA UT WOS:000261148500004 PM 18984376 ER PT J AU Shipherd, JC Salters-Pedneault, K AF Shipherd, Jillian C. Salters-Pedneault, Kristalyn TI Attention, Memory, Intrusive Thoughts, and Acceptance In PTSD: An Update on the Empirical Literature for Clinicians SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; WRITTEN EMOTIONAL EXPRESSION; RANDOMIZED CONTROLLED-TRIAL; FEAR-POTENTIATED STARTLE; MOTOR-VEHICLE ACCIDENTS; D-CYCLOSERINE; EXPERIENTIAL AVOIDANCE; ANXIETY DISORDERS; CONDITIONED FEAR AB Information processing theory suggests that cognitive changes following trauma are common and hypothesized to have all impact on attention, memory, and intrusive thoughts. Their is an ever-expanding empirical literature where cognitive features of posttraumatic stress disorder (PTSD) are being explored. However, it can sometimes be difficult for front-line clinicians to stay abreast of this literature and how it impacts the treatment s/he provides. The goal of this paper is to provide an overview of some recent basic and applied research an information processing in PTSD and the implications of these findings for cognitive-behavior at clinicians. In particular, we explore recent findings regarding attention, memory, intrusive thoughts/thought suppression, and acceptance as they relate to clinical work in patients with PTSD. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Shipherd, JC (reprint author), Vet Adm Med Ctr Jamaica Plain, 116B-3,150 S Huntington Ave, Boston, MA 02130 USA. EM Jillian.Shipherd@va.gov NR 191 TC 18 Z9 18 U1 6 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2008 VL 15 IS 4 BP 349 EP 363 DI 10.1016/j.cbpra.2008.01.003 PG 15 WC Psychology, Clinical SC Psychology GA 372JO UT WOS:000260898100001 ER PT J AU Thompson-Brenner, H Eddy, KT Franko, DL Dorer, DJ Vashchenko, M Kass, AE Herzog, DB AF Thompson-Brenner, Heather Eddy, Kamryn T. Franko, Debra L. Dorer, David J. Vashchenko, Maryna Kass, Andrea E. Herzog, David B. TI A personality classification system for eating disorders: a longitudinal study SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID BULIMIA-NERVOSA; ANOREXIA-NERVOSA; FOLLOW-UP; SHORT-TERM; AXIS-II; PREDICTORS; WOMEN; RELIABILITY; SUBTYPES; COMORBIDITY AB Background: Studies of eating disorders (EDs) suggest that empirically derived personality subtypes may explain heterogeneity in ED samples that is not captured by the Current diagnostic system. Longitudinal Outcomes for personality subtypes have not been examined. Method: In this study. personality pathology was assessed by clinical interview in 213 individuals with anorexia nervosa and bulimia nervosa at baseline. Interview data oil EDs, comorbid diagnoses, global functioning. and treatment utilization were collected at baseline and at 6-month Follow-up intervals over a median of 9 years. Results: Q-factor analysis of the participants based oil personality items produced a 5-prototype system. including high-functioning,, behaviorally dysregulated, emotionally dysregulated, avoidant-insecure, and obsessional-sensitive types. Dimensional prototype scores were associated with baseline functioning and longitudinal outcome. Avoidant-Insecure scores showed consistent associations with poor functioning and outcome. including failure to show ED improvement, poor global functioning after 5 years, and high treatment utilization after 5 years. Behavioral dysregulation was associated with poor baseline functioning but did not show strong associations with ED or global outcome when histories of major depression and substance use disorder were covaried. Emotional dysregulation and obsessional-sensitivity were not associated with negative Outcomes. High-functioning prototype scores were consistently associated with positive outcomes. Conclusions: Longitudinal results Support the importance of personality subtypes to ED classification. (C) 2008 Elsevier Inc. All rights reserved. C1 [Thompson-Brenner, Heather; Eddy, Kamryn T.; Franko, Debra L.; Dorer, David J.; Vashchenko, Maryna; Kass, Andrea E.; Herzog, David B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thompson-Brenner, H (reprint author), Massachusetts Gen Hosp, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM ht41@hotmail.com FU NIAAA NIH HHS [R03 AA 13614-0198]; NIDA NIH HHS [R03 DA015414-01A1]; NIMH NIH HHS [5R01 MH 38333-05, K23 MH071641-01A2, K23 MH071641] NR 59 TC 33 Z9 33 U1 2 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 2008 VL 49 IS 6 BP 551 EP 560 DI 10.1016/j.comppsych.2008.04.002 PG 10 WC Psychiatry SC Psychiatry GA 373YY UT WOS:000261010600005 PM 18970903 ER PT J AU Feng, QZ Zhao, YS Abdelwahid, E AF Feng, Quan-Zhou Zhao, Yu-Sheng Abdelwahid, Eltyeb TI The role of Fas in the progression of ischemic heart failure: prohypertrophy or proapoptosis SO CORONARY ARTERY DISEASE LA English DT Article DE apoptosis; Fas; heart failure; hypertrophy; myocardial ischemia/infarction ID TUMOR-NECROSIS-FACTOR; MYOCYTE CELL-DEATH; ACUTE MYOCARDIAL-INFARCTION; FAS/FAS LIGAND SYSTEM; CARDIAC MYOCYTES; IN-VIVO; INDUCED APOPTOSIS; TRANSCRIPTION FACTOR; MEDIATED APOPTOSIS; MOLECULAR-CLONING AB During myocardial ischemia, cardiomyocytes can undergo apoptosis or compensatory hypertrophy. Fas expression is upregulated in the myocardial ischemia and is coupled to both apoptosis and hypertrophy of cardiomyocytes. The role of Fas in apoptosis induction or cardiomyocyte hypertrophy during ischemic conditions is, however, still unclear. Some reports suggested that Fas might induce myocardial hypertrophy. Apoptosis of ischemic cardiomyocytes and Fas expression in the nonischemic cardiomyocytes occurs during the early stage of ischemic heart failure. Hypertrophic cardiomyocytes easily undergo apoptosis in response to ischemia, after which apoptotic cardiomyocytes are replaced by fibrous tissue. In the late stage of ischemic heart failure, hypertrophy, apoptosis, and fibrosis are thought to accelerate each other and might thus form a vicious circle that eventually results in heart failure. In this review, we summarize recent advances in the understanding of the role of Fas in remodeling ischemic myocardial tissues. Coron Artery Dis 19:527-534 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Feng, Quan-Zhou; Zhao, Yu-Sheng] Chinese Peoples Liberat Army Gen Hosp, Inst Geriatr Cardiol, Beijing 100853, Peoples R China. [Abdelwahid, Eltyeb] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC, Charlestown, MA USA. RP Feng, QZ (reprint author), Chinese Peoples Liberat Army Gen Hosp, Inst Geriatr Cardiol, Fuxing Rd 28, Beijing 100853, Peoples R China. EM fqz301@yahoo.com FU National Natural Science Foundation of China [30570734] FX This paper was supported by the National Natural Science Foundation of China (30570734). NR 62 TC 9 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD NOV PY 2008 VL 19 IS 7 BP 527 EP 534 DI 10.1097/MCA.0b013e3283093707 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 366YV UT WOS:000260520400015 PM 18923250 ER PT J AU Owens, RL Hess, DR Malhotra, A Venegas, JG Harris, RS AF Owens, Robert L. Hess, Dean R. Malhotra, Atul Venegas, Jose G. Harris, R. Scott TI Effect of the chest wall on pressure-volume curve analysis of acute respiratory distress syndrome lungs SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; mechanical ventilation; static pressure-volume curve; chest wall; esophageal balloon; lung mechanics ID LOWER INFLECTION POINT; END-EXPIRATORY PRESSURE; TRANSPULMONARY PRESSURES; CONTROLLED-TRIAL; RECRUITMENT; ESOPHAGEAL; MECHANICS; FAILURE; INJURY; VENTILATION AB Objective: Previously published methods to assess the chest wall effect on total respiratory system pressure-volume (P-V) curves in acute respiratory distress syndrome have been performed on the lung and chest wall in isolation. We sought to quantify the effect of the chest wall by considering the chest wall and lung in series. Design: Prospective study. Setting. Academic health center medical and surgical intensive care units. Patients: Twenty-two patients with acute respiratory distress syndrome/acute lung injury. Interventions. Using a sigmoidal equation, we fit the pressure-volume data of the lung alone, and defined for each curve the pressure at the point of maximum compliance increase (P(mci)), decrease (P(mcd)), and the point of inflection (P(inf)). We calculated the pressure to which the total respiratory system must be inflated to achieve a volume that would place the lung at each point of interest. We compared these "corrected" pressures (P(mci,c), P(mcd,c), and P(inf,c)) to the measured values of the total respiratory system. Measurements and Main Results. The average difference between P(mci) and P(mci,c) was 0.12 cm H(2)O on inflation (2SD = 5.6 cm H(2)O) and -1.4 cm H(2)O on deflation (2SD = 5.0 cm H(2)O); between P(mcd) and P(mcd,c) was 1.73 cm H(2)O on inflation (2SD = 4.5 cm H(2)O) and -0.15 cm H(2)O on deflation (2SD = 4.9 cm H(2)O); and between P(inf) and P(inf,c), was 0.14 cm H(2)O on inflation (2SD = 6.7 cm H(2)O) and -0.35 cm H(2)O on deflation (2SD = 5.0 cm H(2)O). Conclusions: This method of "correcting" the total respiratory system P-V curve for the chest wall allows for calculation of an airway pressure that would place the lung at a desired volume on its P-V curve. For most patients, the chest wall had little influence on the total respiratory system P-V curve. However, there were patients in whom the chest wall did potentially have clinical significance. (Crit Care Med 2008; 36:2980-2985) C1 [Owens, Robert L.; Harris, R. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. [Hess, Dean R.; Venegas, Jose G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA USA. [Malhotra, Atul] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Harris, RS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. EM rsharris@massmed.org FU U.S. National Heart, Lung, and Blood Institute [HL04501] FX Supported in part by a grant from the U.S. National Heart, Lung, and Blood Institute, HL04501. NR 27 TC 15 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2008 VL 36 IS 11 BP 2980 EP 2985 DI 10.1097/CCM.0b013e318186afcb PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 369KU UT WOS:000260694200003 PM 18824918 ER PT J AU Kumwilaisak, K Noto, A Schmidt, UH Beck, CI Crimi, C Lewandrowski, K Bigatello, LM AF Kumwilaisak, Kanya Noto, Alberto Schmidt, Ulrich H. Beck, Clare I. Crimi, Claudia Lewandrowski, Kent Bigatello, Luca M. TI Effect of laboratory testing guidelines on the utilization of tests and order entries in a surgical intensive care unit SO CRITICAL CARE MEDICINE LA English DT Article DE diagnostic testing; laboratory tests guidelines; intensive care unit resource utilization; intensive care unit quality assurance ID ANCILLARY COST REDUCTION; CRITICALLY-ILL; BLOOD-LOSS; ARTERIAL LINES; TRANSFUSION; PHYSICIANS; ANEMIA; IMPROVEMENT; DURABILITY; STRATEGY AB Objective. Diagnostic testing is frequently overused in the intensive care unit. We devised guidelines to optimize blood tests utilization, and designed this study to quantify their efficacy over time, their safety, and their possible benefits. Design: Laboratory testing guidelines were created by consensus and implemented through repeated staff education. The guidelines included: a) the tests to be obtained daily: complete blood count, serum electrolytes, urea nitrogen, creatinine, and blood glucose concentration; b) the need to discuss laboratory testing at daily patient's rounds; c) the need to provide a written order for all tests. The number of tests performed, corresponding physician orders, and various outcome measures were collected for two 6-month study periods, before and after the first day of implementation of the guidelines. Setting: Twenty-bed surgical intensive care unit in a tertiary care teaching hospital. Patients. All patients admitted during the two study periods. Methods. Laboratory tests and related physician orders, demographics, blood products transfusion, and outcomes were collected from hospital databases. In prospectively defined subgroups, additional outcome measures were obtained by ad-hoc chart review. Results: One thousand one hundred seventeen patients were enrolled. After the institution of the guidelines, the number of laboratory tests decreased by 37% (from 64,305 to 40,877), and the number of respective physician orders increased by 38% (from 20,940 to 35,472), p < 0.001. These results were manifest within 1 month, sustained through the study period, and still present at 1 yr. No changes in outcomes or in the rates of selected complications were detected. Red blood cells utilization correlated linearly (12.47) with the number of blood tests performed in both study periods. Conclusions: Guidelines designed to optimize laboratory tests use in an intensive care unit can produce rapid and long-lasting effects, can be safe, and may affect the number of red blood cell units transfused. (Crit Care Med 2008; 36:2993-2999) C1 [Bigatello, Luca M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Crit Care Div, Boston, MA 02114 USA. [Kumwilaisak, Kanya] Chulalongkorn Univ, Fac Med, Dept Anesthesia, Bangkok 10330, Thailand. [Noto, Alberto] Univ Messina, Policlin G Martino, Dept Cardiothorac & Vasc Anesthesia, Messina, Italy. [Schmidt, Ulrich H.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Resp Acute Care Unit, Boston, MA 02114 USA. [Beck, Clare I.] Massachusetts Gen Hosp, Surg Intens Care Unit, Boston, MA 02114 USA. [Lewandrowski, Kent] Harvard Univ, Sch Med, Boston, MA USA. RP Bigatello, LM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Crit Care Div, Boston, MA 02114 USA. EM lbigatello@partners.org RI Noto, Alberto/G-6468-2012 FU NIA NIH HHS [P30 AG028717] NR 33 TC 27 Z9 27 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2008 VL 36 IS 11 BP 2993 EP 2999 DI 10.1097/CCM.0b013e31818b3a9d PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 369KU UT WOS:000260694200005 PM 18824907 ER PT J AU Kahn, JM Branas, CC Schwab, CW Asch, DA AF Kahn, Jeremy M. Branas, Charles C. Schwab, C. William Asch, David A. TI Regionalization of medical critical care: What can we learn from the trauma experience? SO CRITICAL CARE MEDICINE LA English DT Review DE intensive care; patient transport; triage ID INTENSIVE-CARE; UNITED-STATES; MAJOR TRAUMA; MECHANICAL VENTILATION; SYSTEM-DEVELOPMENT; OUTCOMES; MORTALITY; VOLUME; ILL; ORGANIZATION AB Objective: To review the rationale for the regionalization of adult critical care and discuss how lessons from the trauma experience may be relevant to this debate. Design: Narrative review and opinion. Results. Variation in the quality of critical care among hospitals has prompted calls for regionalization of care for critically ill patients. Because of similarities between trauma and critical care, trauma is often cited as a model for the regionalization of critical care services. In reality, there are both important similarities and differences between trauma and critical care. In addition, many lessons from the trauma experience directly apply to future efforts to regionalize critical care services. In this article, we review the analogy between the regionalization of trauma and critical care and discuss how the trauma experience both supports and limits the argument for creation of a formal regionalized system of care for the critically ill. If regionalization efforts in critical care are to proceed, the lessons of the trauma experience can inform policy decisions and provide insight into the design and implementation of an effective regionalized system. (Crit Care Med 2008; 36:3085-3088) C1 [Kahn, Jeremy M.] Univ Penn, Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Branas, Charles C.; Schwab, C. William] Univ Penn, Sch Med, Div Traumatol & Surg Crit Care, Philadelphia, PA 19104 USA. [Kahn, Jeremy M.; Branas, Charles C.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Kahn, Jeremy M.; Branas, Charles C.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Kahn, JM (reprint author), Univ Penn, Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. EM jmkahn@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X NR 41 TC 43 Z9 43 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 NOV PY 2008 VL 36 IS 11 BP 3085 EP 3088 DI 10.1097/CCM.0b013e31818c37b2 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 369KU UT WOS:000260694200020 PM 18824900 ER PT J AU Kaneki, M Sakai, M Shimizu, N Chang, K AF Kaneki, Masao Sakai, Michihiro Shimizu, Nobuyuki Chang, Kyungho TI Is normalized mean blood glucose level good enough for the intensive care unit? Glycemic variability as a new independent predictor of mortality SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE glycemic variability; intensive insulin treatment; intensive care unit; mortality; blood glucose ID CRITICALLY-ILL PATIENTS; INSULIN THERAPY; HYPERGLYCEMIA C1 [Kaneki, Masao; Sakai, Michihiro] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. [Shimizu, Nobuyuki] Univ Tokyo, Grad Sch Med, Dept Gastrointestinal Surg, Tokyo, Japan. [Chang, Kyungho] Univ Tokyo, Grad Sch Med, Dept Anesthesia & Pain Relief Ctr, 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 15 TC 4 Z9 4 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 NOV PY 2008 VL 36 IS 11 BP 3104 EP 3106 DI 10.1097/CCM.0b013e31818c38ab PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 369KU UT WOS:000260694200028 PM 18941315 ER PT J AU van Kimmenade, RRJ Bajwa, E Januzzi, JL AF van Kimmenade, Roland R. J. Bajwa, Ednan Januzzi, James L. TI Sepsis and those who are "weak of heart" SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE natriuretic peptides; B-type natriuretic peptide; NT-proBNP; sepsis; intensive care; outcomes ID BRAIN NATRIURETIC PEPTIDE; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; PROGNOSTIC VALUE; FAILURE; DIAGNOSIS; SHOCK C1 [van Kimmenade, Roland R. J.; Bajwa, Ednan] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.; Bajwa, Ednan] Massachusetts Gen Hosp, Div Crit Care, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP van Kimmenade, RRJ (reprint author), Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. RI Kimmenade, R.R.J./L-4432-2015 NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2008 VL 36 IS 11 BP 3108 EP 3109 DI 10.1097/CCM.0b013e31818bdc4a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 369KU UT WOS:000260694200030 PM 18941317 ER PT J AU Sangwaiya, MJ Zalis, ME Saini, S AF Sangwaiya, Minal Jagtiani Zalis, Michael E. Saini, Sanjay TI Current Status of CT Colonography SO CURRENT MEDICAL IMAGING REVIEWS LA English DT Review DE Colorectal cancer; screening; CT colonography; virtual colonoscopy ID COLORECTAL-CANCER; VIRTUAL COLONOSCOPY; COST-EFFECTIVENESS; NEOPLASIA AB Colorectal cancer (CRC) is the third most common form of cancer and the second leading cause of cancer related mortality in the United States. Most cases of CRC however can be prevented through early detection and removal of pre-cancerous adenomatous polyps. This strategy is based on the "polyp-to-cancer" sequence suggested by Vogelstein. Even though the American Cancer Society (ACS) began advocating CRC prevention in the early 1980s and Medicare began reimbursement for CRC in 2001 in the US, approximately 50 million adults have never been screened for CRC. As a result, over 150,000 new cases of CRC are diagnosed each year. Recently, the ACS endorsed the use of CT Colonography for CRC screening in asymptomatic adults with average risk (for developing CRC) starting at age 50. Scanning and interpretation techniques for CT Colonography (virtual colonoscopy) have evolved considerably since it was first introduced by Vining in 1994. Thus, for lesions >5mm, the performance of CTC is comparable to that of optical colonoscopy (OC). Our aim is to describe the optimal technique for CTC and define its role in the colorectal cancer screening strategy. C1 [Sangwaiya, Minal Jagtiani; Zalis, Michael E.; Saini, Sanjay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sangwaiya, MJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mjagtiani@partners.org NR 14 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4056 J9 CURR MED IMAGING REV JI Curr. Med. Imaging Rev. PD NOV PY 2008 VL 4 IS 4 BP 222 EP 225 DI 10.2174/157340508786404080 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386OL UT WOS:000261892400003 ER PT J AU Osborn, EA Jaffer, FA AF Osborn, Eric A. Jaffer, Farouc A. TI Advances in molecular imaging of atherosclerotic vascular disease SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE atherosclerosis; imaging; molecular imaging; myocardial infarction; stroke ID POSITRON-EMISSION-TOMOGRAPHY; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; RISK-ASSESSMENT STRATEGIES; CELL-ADHESION MOLECULE-1; OXIDE-ENHANCED MRI; IN-VIVO; PLAQUE INFLAMMATION; IRON-OXIDE; CARDIOVASCULAR-DISEASE; NONINVASIVE DETECTION AB Purpose of review Molecular imaging aims to illuminate vital molecular and cellular aspects of disease in vivo, and is rapidly translating into the clinical arena. Advantages of this field include enabling serial biological studies in living subjects, assessment of pharmaceutical efficacy, and in-vivo characterization of clinical diseases. Here we present recent exciting advances in molecular imaging of atherosclerotic vascular disease. Recent findings Atherosclerosis molecular imaging approaches are now available for magnetic resonance, nuclear, computed tomography, ultrasound, and near-infrared fluorescence imaging. Advances in agent synthesis and detection technology are now enabling in-vivo imaging of endothelial cell activation, macrophages, cellular metabolism, protease activity, apoptosis, and osteogenic activity. Several agents show clinical utility for the detection of high-risk plaques. Summary Molecular imaging is actively unraveling the biological basis of atherosclerosis in living subjects. In the near-term, molecular imaging will play an important role in assessing novel atherosclerosis pharmacotherapies in clinical trials. Longer term, molecular imaging should enable accurate identification of high-risk plaques responsible for myocardial infarction, stroke, and ischemic limbs. C1 [Osborn, Eric A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiovasc Res Ctr, Richard B Simches Res Ctr,Cardiol Div, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiovasc Res Ctr, Richard B Simches Res Ctr,Cardiol Div, Charles River Plaza,185 Cambridge St,Suite 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU Howard Hughes Medical Institute; American Heart Association; Donald W. Reynolds foundation FX Supported by the Howard Hughes Medical Institute Early Career Award (F.J.), American Heart Association Scientist Development Grant (F.J.), and Donald W. Reynolds foundation (F.J.). NR 38 TC 16 Z9 19 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2008 VL 23 IS 6 BP 620 EP 628 DI 10.1097/HCO.0b013e328310fc7e PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 365KR UT WOS:000260405800015 PM 18830079 ER PT J AU Nelson, A Hartl, W Jauch, KW Fricchione, GL Benson, H Warshaw, AL Conrad, C AF Nelson, Aaron Hartl, Wolfgang Jauch, Karl-Walter Fricchione, Gregory L. Benson, Herbert Warshaw, Andrew L. Conrad, Claudius TI The impact of music on hypermetabolism in critical illness SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Editorial Material DE complementary therapy; hypermetabolic syndrome; music; systemic inflammatory response syndrome; stress hormone ID HORMONE-RELEASING HORMONE; GROWTH-HORMONE; ENERGY-EXPENDITURE; BLOOD-PRESSURE; IMMUNE-SYSTEM; EXPRESSION; MICE; NEUROENDOCRINE; INFUSION; CORTISOL AB Purpose of review Although the literature on complementary therapy, including music, is vast, there are few studies conducted in a scientific fashion exploring physiologic mechanisms. This review summarizes recent evidence on the effects of music on the hypermetabolic response of critical illness. Recent findings Music may restore some of the distorted homeostasis observed in ICU patients, as well as reducing pain and the need for sedation. Music likely reduces alterations in the hypothalamic-anterior pituitary-peripheral hormone axes that produce cortisol and growth hormone. Music may also increase growth hormone levels, which can induce decreased production of cytokines such as IL-6 by white blood cells. Further, ovarian steroid secretion may paradoxically protect women by increasing baseline circulating stress hormones, providing an opportunity for music therapy to intervene effectively. Dopaminergic neurotransmission has been implicated as a means by which music can modulate the central nervous system. Summary Music may play an important role as an adjunct therapy in critical care. However, further studies are necessary to elucidate how music can be further integrated clinically and the precise underlying mechanisms of its beneficial effects. C1 [Nelson, Aaron; Warshaw, Andrew L.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Hartl, Wolfgang; Jauch, Karl-Walter] Univ Munich Grosshadern, Dept Surg, Munich, Germany. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Fricchione, Gregory L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Benson, Herbert] Massachusetts Gen Hosp, Benson Henry Inst, Boston, MA 02114 USA. RP Conrad, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM Cconrad1@partners.org NR 33 TC 15 Z9 16 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD NOV PY 2008 VL 11 IS 6 BP 790 EP 794 DI 10.1097/MCO.0b013e328314dd01 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 368KI UT WOS:000260619600017 PM 18827585 ER PT J AU Ham, M Kaunitz, JD AF Ham, Maggie Kaunitz, Jonathan D. TI Gastroduodenal mucosal defense SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE bicarbonate; cyclooxygenase inhibitors; duodenum; leptin; matrix metalloproteinase; orexins; stomach; survivin ID NITRIC-OXIDE SYNTHASE; DUODENAL BICARBONATE SECRETION; INDUCED GASTRIC INJURY; HELICOBACTER-PYLORI; GASTROINTESTINAL COMPLICATIONS; HCO3-SECRETION; EXPRESSION; ULCER; RAT; PROTECTION AB Purpose of review The gastrointestinal tract has developed multi le mechanisms of protection intrinsic and extrinsic sources of injury, including but not limited to drugs, ischemic/reperfusion injuries, and infections such as Helicobacter pylori. We review recent developments in host defense against Helicobacter pylori, duodenal bicarbonate secretion, protection from nonsteroidal anti-inflammatory drug induced gastrointestinal injury, and apoptosis, as well as newer therapies. Recent findings Leptin and survivin confer protection against ethanol and indomethacin induced injury. Mucin-1, a cell surface mucin, is an important barrier to gastrointestinal infection. Prostaglandin E-2, Escherichia coli heat-stable enterotoxin, orexins, and carbonated beverages stimulate duodenal bicarbonate secretion. Summary Gastroduodenal mucosal defense is a dynamic process, and further insights into these defense mechanisms have and will lead to safer and more effective treatments. C1 [Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Ham, Maggie; Kaunitz, Jonathan D.] Sch Med, Dept Med, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01 DK054221] NR 50 TC 15 Z9 15 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2008 VL 24 IS 6 BP 665 EP 673 DI 10.1097/MOG.0b013e328311cd93 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 374AE UT WOS:000261013800003 PM 19122513 ER PT J AU El-Zimaity, H AF El-Zimaity, Hala TI Gastritis and gastric atrophy SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE atrophy; gastritis; staging ID HELICOBACTER-PYLORI GASTRITIS; DUODENAL-ULCER PATIENTS; INTESTINAL METAPLASIA; PEPTIC-ULCER; PERNICIOUS-ANEMIA; MAJOR AUTOANTIGEN; CORPUS GASTRITIS; HIGH PREVALENCE; SYDNEY SYSTEM; PEPSINOGEN-I AB Purpose of review The majority of problems in interpreting gastritis remain Helicobacter related, but their nature has changed. The present review covers gastritis historically through cancer risk staging systems. Recent findings Key points to remember are: Helicobacter is associated with several forms of gastritis; in the present review, I am focusing on the two ends of the disease, Helicobacter pylori infection', that starts with antral predominant gastritis but can continue to oxyntic predominant disease with atrophy; the role Helicobacter pylori plays in autoimmune gastritis with pernicious anemia remains unresolved; gastritis staging systems for cancer risk, namely Baylor and Operative Link on Gastritis Assessment, are currently available. Summary As most gastric carcinomas arise on a background of atrophic gastritis, and the risk increases with the extent of atrophy, an index of atrophy location and extent could be useful in predicting patients at greatest risk for carcinoma. It is now possible to stage patients for cancer risk. Nonetheless, in a field such as gastritis in which many issues remain unresolved, a classification or staging system that is more descriptive will likely prove more useful. C1 [El-Zimaity, Hala] McMaster Univ, Dept Pathol, Hamilton, ON, Canada. [El-Zimaity, Hala] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP El-Zimaity, H (reprint author), McMaster Div, 1200 Main St W,RM 2N31, Hamilton, ON L8S 3Z5, Canada. EM zimaity@mcmaster.ca NR 50 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2008 VL 24 IS 6 BP 682 EP 686 DI 10.1097/MOG.0b013e328311d1cc PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 374AE UT WOS:000261013800005 PM 19122515 ER PT J AU Boden, EK Snapper, SB AF Boden, Elisa K. Snapper, Scott B. TI Regulatory T cells in inflammatory bowel disease SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE Crohn's disease; inflammatory bowel disease; mucosal immunology; regulatory T cells; ulcerative colitis ID WISKOTT-ALDRICH-SYNDROME; GROWTH-FACTOR-BETA; TRANSCRIPTION FACTOR FOXP3; INNATE IMMUNE PATHOLOGY; TGF-BETA; INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; DENDRITIC CELLS; CROHNS-DISEASE; CUTTING EDGE AB Purpose of review The intestinal immune system must orchestrate a complex balance between proinflammatory and anti-inflammatory responses to luminal antigens, and disruptions in this balance can result in inflammatory bowel disease (IBD). This review explores recent data that elucidate the role of regulatory T cells (Tregs) in the pathogenesis of IBD in mice and humans. Recent findings Data from murine models of colitis implicate several novel mechanisms critical to Treg function and generation including the inhibitory cytokine interleukin-35, pericellular adenosine generation and cytokine deprivation-induced apoptosis. Although Tregs are essential in mice for the maintenance of intestinal homeostasis, their role in human IBD remains unclear. Patients with IBD appear to have relatively reduced numbers of Tregs in the blood and colon; however, Tregs from these patients are functional in vitro. Summary Tregs are important for the maintenance of intestinal self-tolerance and will likely prove to be an important avenue for therapeutic manipulation in IBD. C1 [Snapper, Scott B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Snapper, SB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, 55 Blossom St, Boston, MA 02114 USA. EM ssnapper@nms.harvard.edu FU NIH [T32 DK007191, HL059561, Al50950] FX The authors would like to thank D. Nguyen, V. Ahuja, L. Westerberg, J. R. Mora, and W. Faubion for a careful review of this manuscript. This work was funded by NIH grants T32 DK007191 to EB and HL059561 and Al50950 to SBS. NR 121 TC 70 Z9 72 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2008 VL 24 IS 6 BP 733 EP 741 DI 10.1097/MOG.0b013e328311f26e PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 374AE UT WOS:000261013800014 PM 19125486 ER PT J AU Norden, AD Drappatz, J Wen, PY AF Norden, Andrew D. Drappatz, Jan Wen, Patrick Y. TI Antiangiogenic therapy in malignant gliomas SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE angiogenesis; glioblastoma; malignant glioma ID PHASE-II TRIAL; ENDOTHELIAL-GROWTH-FACTOR; HIGH-GRADE GLIOMAS; RECURRENT GLIOBLASTOMA-MULTIFORME; BRAIN-TUMOR CONSORTIUM; ANAPLASTIC ASTROCYTOMA; STEM-CELLS; IN-VIVO; METRONOMIC CHEMOTHERAPY; CILENGITIDE EMD121974 AB Purpose of review Antiangiogenic drugs are increasingly used in malignant glioma therapy. This article reviews the rationale for targeting angiogenesis in malignant gliomas, summarizes relevant clinical trial results, and discusses promising avenues of investigation in antiangiogenic therapy. Recent findings Combination therapy with bevacizumab, the humanized monoclonal antibody against vascular endothelial growth factor, and irinotecan has emerged as the treatment of choice for recurrent malignant gliomas, prolonging progression-free survival markedly in comparison with historical controls. Several small molecule tyrosine kinase inhibitors of the vascular endothelial growth factor receptor are under investigation and show promise as well. Summary Antiangiogenic treatments are effective and well tolerated options for recurrent malignant glioma, Future studies will determine whether these drugs have a role in first line therapy. Studies are in progress to elucidate mechanisms of resistance and suggest approaches to further improve survival in patients with these challenging tumors. C1 [Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurooncol, Dept Neurol, Boston, MA 02115 USA. [Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Ctr Neurooncol, Boston, MA USA. [Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Norden, AD (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 44 Binney St, Boston, MA 02115 USA. EM anorden@partners.org FU Amos E. Wasgatt and Neil Harrington Brain Tumor Research FX We gratefully acknowledge the support of the Amos E. Wasgatt and Neil Harrington Brain Tumor Research Funds. NR 85 TC 31 Z9 32 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2008 VL 20 IS 6 BP 652 EP 661 DI 10.1097/CCO.0b013e32831186ba PG 10 WC Oncology SC Oncology GA 369ND UT WOS:000260700300008 PM 18841047 ER PT J AU Gottlieb, DJ AF Gottlieb, Daniel J. TI The Sleep Heart Health Study: a progress report SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article DE cardiovascular disease; epidemiology; sleep; sleep apnea; sleep-disordered breathing ID APOLIPOPROTEIN-E EPSILON-4; RESTLESS LEGS SYNDROME; CARDIOVASCULAR-DISEASE; ASSOCIATION; HYPERTENSION; APNEA AB Purpose of review The Sleep Heart Health Study began in 1994 as a prospective cohort study of cardiovascular disease. The results of longitudinal analysis are not yet available, but numerous analyses of cross-sectional data have been published. This review provides an overview of study results so far. Recent findings Recent findings covered in this review include a methodological study supporting the choice of a 4% oxyhemoglobin desaturation criterion for identification of hypopneas; evidence that sleepiness may modify the association of sleep apnea with hypertension; the association of sleep apnea with increased left ventricular mass in a pattern suggesting predominantly eccentric left ventricular hypertrophy; the association of restless legs syndrome with an increase in prevalent cardiovascular disease; and the results of a genome-wide association study of sleep and circadian phenotypes. Summary Although designed as a prospective cohort study, analysis of cross-sectional data from the Sleep Heart Health Study has contributed numerous insights to the field of sleep medicine. C1 [Gottlieb, Daniel J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. RP Gottlieb, DJ (reprint author), Boston Univ, Sch Med, 715 Albany St,R-304, Boston, MA 02118 USA. EM gottlieb@bu.edu FU [U01 HL53941] FX The Sleep Heart Health Study was funded by multiple cooperative agreements, including U01 HL53941 to Boston University. NR 26 TC 8 Z9 8 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD NOV PY 2008 VL 14 IS 6 BP 537 EP 542 DI 10.1097/MCP.0b013e328312ed61 PG 6 WC Respiratory System SC Respiratory System GA 361SK UT WOS:000260147200006 PM 18812830 ER PT J AU Gretsov, E Barteneva, N Vorobjev, I AF Gretsov, Eugeny Barteneva, Natasha Vorobjev, Ivan TI CD38 EXPRESSION IN CLL CORRELATES WITH THE PROLIFERATION INDEX AND DOES NOT CORRELATE WITH CD25 AND BCL-2 EXPRESSION SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 23rd Annual Meeting of the Clinical-Cytometry-Society CY OCT 12-14, 2008 CL Portland, OR SP Clinical Cytometry Soc C1 [Gretsov, Eugeny; Vorobjev, Ivan] Harvard Univ, Sch Med, Hematol Res Ctr, Cambridge, MA 02138 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Immune Dis Inst, Cambridge, MA 02138 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2008 VL 74B IS 6 BP 369 EP 369 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 366AZ UT WOS:000260453200020 ER PT J AU Huang, MQ Sage, C Li, HW Xiang, MQ Heller, S Chen, ZY AF Huang, Mingqian Sage, Cyrille Li, Huawei Xiang, Mengquig Heller, Stefan Chen, Zheng-Yi TI Diverse Expression Patterns of LIM-Homeodomain Transcription Factors (LIM-HDs) in Mammalian Inner Ear Development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE LIM-HD; development; Inner ear; hair cells; differentiation ID HAIR CELL-DEVELOPMENT; MATURE GUINEA-PIGS; MOTOR-NEURON; RETINOBLASTOMA PROTEIN; FATE DETERMINATION; SENSORY EPITHELIA; DREHER GENE; IN-VIVO; MATH1; IDENTITY AB LIM-homeodomain transcription factors (LIM-HDs) are essential in tissue patterning and differentiation. But their expression patterns in the inner ear are largely unknown. Here we report on a study of twelve LIM-HDs, by their tempo-spatial patterns that imply distinct yet overlapping roles, in the developing mouse inner ear. Expression of Lmx1a and Isl1 begins in the otocyst stage, with Lntx1a exclusively in the nonsensory and Isl1 in the prosensory epithelia. The second wave of expression at E12.5 includes Lhx3, 5,9, Isl2, and Lmx1b in the differentiating sensory epithelia with cellular specificities. With the exception of Lmx1a and Lhx3, all LIM-HDs are expressed in ganglion neurons. Expression of multiple LIM-HDs within a cell type suggests their redundant function. Developmental Dynamics 237.3305-3312, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Huang, Mingqian; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Huang, Mingqian; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Sage, Cyrille] Hop Henri Mondor, INSERM, U 654, F-94010 Creteil, France. [Li, Huawei] Fudan Univ, Inst Hearing Res, Otol Skull Base Surg Dept, Shanghai 200433, Peoples R China. [Xiang, Mengquig] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Dept Pediat, Piscataway, NJ 08854 USA. [Heller, Stefan] Stanford Univ, Dept Otolaryngol Head & Neck Surg, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA. RP Chen, ZY (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Zheng-Yi_Chen@meei.harvard.edu FU NIH [DC-04546, DC-06908, DC-6167]; DRF foundation FX We thank Dr. Joe Adams for his constructive comments on the manuscript. The project was supported by NIH grants DC-04546, DC-06908 (Z.Y.C.) and DC-6167 (S.H.). M.H. was supported in part by a grant from the DRF foundation. The research was conducted while Z.-Y.C. was a Pfizer/AFAR Innovation in Aging Research Grant recipient. NR 35 TC 17 Z9 17 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2008 VL 237 IS 11 BP 3305 EP 3312 DI 10.1002/dvdy.21735 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 372VP UT WOS:000260930400020 PM 18942141 ER PT J AU Anguera, MC Liu, M Avruch, J Lee, JT AF Anguera, Montserrat C. Liu, Matthew Avruch, Joseph Lee, Jeannie T. TI Characterization of Two Mst1-Deficient Mouse Models SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Mst1; Sterile 20-like kinases; transmission ratio distortion; gene-trap insertion ID TRANSMISSION RATIO DISTORTION; STE20-LIKE PROTEIN-KINASE; MEIOTIC DRIVE; PROMOTES APOPTOSIS; SEGREGATION DISTORTION; CELL-PROLIFERATION; MST1 KINASE; CHROMATIN CONDENSATION; CASPASE CLEAVAGE; TUMOR-SUPPRESSOR AB Mammalian sterile 20-like kinase 1 (MstI) is a ubiquitously expressed serine/threonine kinase belonging to the family of Sterile 20-like kinases. MST1 has been inferred to play important roles in apoptosis and in the inhibition of proliferation in mammalian cells. Here, we describe the genetic characterization of Mst1-deficient mice produced by two distinct gene-trap insertions. Animals generated from clone RRT293 exhibit transmission ratio distortion favoring the mutated allele which is amplified with each generation. Inexplicably, while the mutated allele is favored for transmission, its homozygosity is embryonic lethal. By contrast, animals generated from the second Mst1 gene-trap clone, AJ0315, do not show any gross abnormalities. We find that the discrepancy in phenotype is most likely attributable to a second insertion in the RRT293 clone. Thus, a mutation in Mst1 alone does not affect survival. Our results set the stage for identification of the lethal second-site mutation that is paradoxically favored for transmission. Developmental Dynamics 237:3424-3434, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Anguera, Montserrat C.; Avruch, Joseph; Lee, Jeannie T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. [Liu, Matthew; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit Med Serv, Boston, MA 02114 USA. [Liu, Matthew; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Avruch, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu; lee@molbio.mgh.harvard.edu FU National Institutes of Health NRSA; Howard Hughes Medical Institute; NIH FX M.C.A was funded by the National Institutes of Health NRSA, J.T.L. received a grant from the Howard Hughes Medical Institute, and J.A. was funded by a NIH grant. NR 55 TC 2 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2008 VL 237 IS 11 BP 3424 EP 3434 DI 10.1002/dvdy.21764 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 372VP UT WOS:000260930400033 PM 18942145 ER PT J AU Bonner-Weir, S O'Brien, TD AF Bonner-Weir, Susan O'Brien, Timothy D. TI Islets in Type 2 Diabetes: In Honor of Dr. Robert C. Turner SO DIABETES LA English DT Article ID BETA-CELL APOPTOSIS; ENDOPLASMIC-RETICULUM STRESS; AMYLOID POLYPEPTIDE; INSULIN-SECRETION; PANCREATIC-ISLETS; HUMAN AMYLIN; LANGERHANS; EXPRESSION; MELLITUS; HUMANS C1 [Bonner-Weir, Susan] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bonner-Weir, Susan] Harvard Univ, Sch Med, Boston, MA USA. [O'Brien, Timothy D.] Univ Minnesota, Dept Vet Populat Med, Minneapolis, MN USA. [O'Brien, Timothy D.] Univ Minnesota, Stem Cell Inst, Minneapolis, MN USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu; obrie004@umn.edu NR 51 TC 40 Z9 40 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 2899 EP 2904 DI 10.2337/db07-1842 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800005 PM 18971437 ER PT J AU O'Rahilly, S Weir, GC Matthews, DR AF O'Rahilly, Stephen Weir, Gordon C. Matthews, David R. TI An Appreciation of Robert Turner SO DIABETES LA English DT Editorial Material ID BLOOD-GLUCOSE CONTROL; BASAL PLASMA-GLUCOSE; BETA-CELL FUNCTION; MICROVASCULAR COMPLICATIONS; INSULIN CONCENTRATIONS; PULSATILE INSULIN; MODEL ASSESSMENT; UKPDS; RISK; ASSOCIATION C1 [Matthews, David R.] Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [O'Rahilly, Stephen] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Weir, Gordon C.] Harvard Univ, Sch Med, Boston, MA USA. RP Matthews, DR (reprint author), Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. EM david.matthews@ocdem.ox.ac.uk NR 30 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 2918 EP 2921 DI 10.2337/db07-1644 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800009 PM 18971441 ER PT J AU Fujii, N Ho, RC Manabe, Y Jessen, N Toyoda, T Holland, WL Summers, SA Hirshman, MF Goodyear, LJ AF Fujii, Nobuharu Ho, Richard C. Manabe, Yasuko Jessen, Niels Toyoda, Taro Holland, William L. Summers, Scott A. Hirshman, Michael F. Goodyear, Laurie J. TI Ablation of AMP-Activated Protein Kinase alpha 2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice SO DIABETES LA English DT Article ID STIMULATED GLUCOSE-UPTAKE; HUMAN SKELETAL-MUSCLE; ZUCKER RATS; IN-VIVO; AICAR; TRANSPORT; CONTRACTION; EXERCISE; GLYCOGEN; GLUT-4 AB OBJECTIVE-We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance. RESEARCH DESIGN AND METHODS-Muscle-specific transgenic mice expressing an inactive form of the AMPK alpha 2 catalytic subunit (alpha 2i TG) and their wild-type littermates were fed either a high-fat (60% kcal fat) or a control (10% kcal fat) diet for 30 weeks. RESULTS-Compared with wild-type mice, glucose tolerance in alpha 2i TG mice was slightly impaired on the control diet and significantly impaired on the high-fat diet. To determine whether the whole-body glucose intolerance was associated with impaired insulin sensitivity in skeletal muscle, glucose transport in response to submaximal insulin (450 mu U/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by similar to 50% in alpha 2i TG mice compared with wild-type mice. High-fat feeding partially decreased insulin-stimulated glucose transport in wild-type mice, while high-fat feeding resulted in a full blunting of insulin-stimulated glucose transport in the alpha 2i TG mice. High-fat feeding in alpha 2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle. CONCLUSIONS-The lack of skeletal muscle AMPK alpha 2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK alpha 2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments. Diabetes 57: 2958-2966, 2008 C1 [Fujii, Nobuharu; Ho, Richard C.; Manabe, Yasuko; Jessen, Niels; Toyoda, Taro; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Res Div, Boston, MA 02115 USA. [Fujii, Nobuharu; Ho, Richard C.; Manabe, Yasuko; Jessen, Niels; Toyoda, Taro; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Holland, William L.; Summers, Scott A.] Univ Utah, Sch Med, Div Endocrinol Diabet & Metab, Salt Lake City, UT USA. RP Goodyear, LJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Res Div, Boston, MA 02115 USA. EM laurie.goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU National Institutes of Health [RO1 AR45670, RO1 DK068626]; DERC [DK36836]; Individual National Research Service Award [F32 AR049662] FX This work was supported by National Institutes of Health Grants RO1 AR45670 and RO1 DK068626 (to L.J.G.), DERC DK36836 at the Joslin Diabetes Center, and the Individual National Research Service Award F32 AR049662 (to R.H.).; We thank Yangfeng Li, Matthew M. Seifert, and Lauren E. Peter for technical assistance. NR 53 TC 58 Z9 61 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 2958 EP 2966 DI 10.2337/db07-1187 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800015 PM 18728234 ER PT J AU Senokuchi, T Liang, CP Seimon, TA Han, S Matsumoto, M Banks, AS Paik, JH DePinho, RA Accili, D Tabas, I Tall, AR AF Senokuchi, Takafumi Liang, Chien-Ping Seimon, Tracie A. Han, Seongah Matsumoto, Michihiro Banks, Alexander S. Paik, Ji-Hye DePinho, Ronald A. Accili, Domenico Tabas, Ira Tall, Alan R. TI Forkhead Transcription Factors (FoxOs) Promote Apoptosis of Insulin-Resistant Macrophages During Cholesterol-Induced Endoplasmic Reticulum Stress SO DIABETES LA English DT Article ID NF-KAPPA-B; ADVANCED ATHEROSCLEROTIC LESIONS; SMOOTH-MUSCLE-CELLS; THERAPEUTIC IMPLICATIONS; OXIDATIVE STRESS; DEFICIENT MICE; FACTOR FKHR; RECEPTOR; PROTEIN; ACTIVATION AB OBJECTIVE-Endoplasmic reticulum stress increases macrophage apoptosis, contributing to the complications of atherosclerosis. Insulin-resistant macrophages are more susceptible to endoplasmic reticulum stress-associated apoptosis probably contributing to macrophage death and necrotic core formation in atherosclerotic plaques in type 2 diabetes. However the molecular mechanisms of increased apoptosis in insulin-resistant macrophages remain unclear. RESEARCH DESIGN AND METHODS-The studies were performed in insulin-resistant macrophages isolated from insulin receptor knockout or ob/ob mice. Gain- or loss-of-function approaches were used to evaluate the roles of forkhead transcription factors (FoxOs) in endoplasmic reticulum stress-associated macrophage apoptosis. RESULTS-Insulin-resistant macrophages showed attenuated Akt activation and increased nuclear localization of FoxO1. during endoplasmic reticulum stress induced by free cholesterol loading. Overexpression of active FoxO1. or FoxO3 failed to induce apoptosis in unchallenged macrophages but exacerbated apoptosis in macrophages with an active endoplasmic reticulum stress response. Conversely, macrophages with genetic knockouts of FoxOl, -3, and 4 were resistant to apoptosis in response to endoplasmic reticulum stress. FoxO1 was shown by chromatin immunoprecipitation and promoter expression analysis to induce inhibitor of kappa B epsilon gene expression and thereby to attenuate the increase of nuclear p65 and nuclear factor-kappa B activity during endoplasmic reticulum stress, with proapoptotic and anti-inflammatory consequences. CONCLUSIONS-Decreased Akt and increased FoxO transcription factor activity during the endoplasmic reticulum stress response leads to increased apoptosis of insulin-resistant macrophages. FoxOs may have a dual cellular function, resulting in either proapoptotic or anti-inflammatory effects in an endoplasmic reticulum stress-modulated manner. In the complex plaque milieu, the ultimate effect is likely to be an increase in macrophage apoptosis, plaque inflammation, and destabilization. Diabetes 57:2967-2976, 2008 C1 [Senokuchi, Takafumi; Liang, Chien-Ping; Seimon, Tracie A.; Han, Seongah; Matsumoto, Michihiro; Banks, Alexander S.; Accili, Domenico; Tabas, Ira; Tall, Alan R.] Columbia Univ, Dept Med, New York, NY 10027 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tabas, Ira; Tall, Alan R.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA. RP Senokuchi, T (reprint author), Columbia Univ, Dept Med, New York, NY 10027 USA. EM senokuchi@fc.kuh.kumamoto-u.ac.jp RI Banks, Alexander/B-4832-2012 OI Banks, Alexander/0000-0003-1787-6925 FU Manpei Suzuki Diabetes Foundation of Tokyo; National Institutes of Health [HL-75662, HL-87123] FX T.S. is the recipient of a research fellowship from the Manpei Suzuki Diabetes Foundation of Tokyo. This work was supported by National Institutes of Health Grants HL-75662 and HL-87123. NR 46 TC 42 Z9 44 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 2967 EP 2976 DI 10.2337/db08-0520 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800016 PM 18728232 ER PT J AU Orho-Melander, M Melander, O Guiducci, C Perez-Martinez, P Corella, D Roos, C Tewhey, R Rieder, MJ Hall, J Abecasis, G Tai, ES Welch, C Arnett, DK Lyssenko, V Lindholm, E Saxena, R de Bakker, PIW Burtt, N Voight, BF Hirschhorn, JN Tucker, KL Hedner, T Tuomi, T Isomaa, B Eriksson, KF Taskinen, MR Wahlstrand, B Hughes, TE Parnell, LD Lai, CQ Berglund, G Peltonen, L Vartiainen, E Jousilahti, P Havulinna, AS Salomaa, V Nilsson, P Groop, L Altshuler, D Ordovas, JM Kathiresan, S AF Orho-Melander, Marju Melander, Olle Guiducci, Candace Perez-Martinez, Pablo Corella, Dolores Roos, Charlotta Tewhey, Ryan Rieder, Mark J. Hall, Jennifer Abecasis, Goncalo Tai, E. Shyong Welch, Cullan Arnett, Donna K. Lyssenko, Valeriya Lindholm, Eero Saxena, Richa de Bakker, Paul I. W. Burtt, Noel Voight, Benjamin F. Hirschhorn, Joel N. Tucker, Katherine L. Hedner, Thomas Tuomi, Tiinaimaija Isomaa, Bo Eriksson, Karl-Fredrik Taskinen, Marja-Riitta Wahlstrand, Bjoern Hughes, Thomas E. Parnell, Laurence D. Lai, Chao-Qiang Berglund, Goran Peltonen, Leena Vartiainen, Erkki Jousilahti, Pekka Havulinna, Aki S. Salomaa, Veikko Nilsson, Peter Groop, Leif Altshuler, David Ordovas, Jose M. Kathiresan, Sekar TI Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; CARDIOVASCULAR MORBIDITY; RISK; POLYMORPHISM; POPULATION; OVEREXPRESSION; HYPERTENSION; SINGAPORE AB OBJECTIVE-Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCYR locus in samples of non-European ancestry and to fine-map across the associated genomic interval. RESEARCH DESIGN AND METHODS-We performed association studies in 12 independent cohorts comprising >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the similar to 417-kb region of linkage disequilibrium. spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval. RESULTS-We provide comprehensive evidence that GCYR rs780094 is associated with opposite effects on fasting plasma triglyceride (P-meta = 3 x 10(-56)) and glucose (P-meta = 1 x 10(-13)) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P = 5 x 10(-5)). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r(2) = 0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS-These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. Diabetes 57:3112-3121, 2008 C1 [Orho-Melander, Marju; Melander, Olle; Roos, Charlotta; Lyssenko, Valeriya; Lindholm, Eero; Eriksson, Karl-Fredrik; Nilsson, Peter; Groop, Leif] Lund Univ, Malmo Gen Hosp, Clin Res Ctr, Dept Clin Sci, S-21401 Malmo, Sweden. [Guiducci, Candace; Tewhey, Ryan; Saxena, Richa; de Bakker, Paul I. W.; Burtt, Noel; Voight, Benjamin F.; Hirschhorn, Joel N.; Altshuler, David; Kathiresan, Sekar] Harvard Univ, Cambridge, MA 02138 USA. [Guiducci, Candace; Tewhey, Ryan; Saxena, Richa; de Bakker, Paul I. W.; Burtt, Noel; Voight, Benjamin F.; Hirschhorn, Joel N.; Altshuler, David; Kathiresan, Sekar] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Perez-Martinez, Pablo] Univ Cordoba, Reina Sofia Univ Hosp, Lipids & Atherosclerosis Res Unit, Cordoba, Spain. [Perez-Martinez, Pablo; Parnell, Laurence D.; Lai, Chao-Qiang; Ordovas, Jose M.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA USA. [Corella, Dolores] Univ Valencia, Sch Med, Genet & Mol Epidemiol Unit, Valencia, Spain. [Corella, Dolores] Univ Valencia, Sch Med, CIBER Fisiopatol Obesidad & Nutr, Valencia, Spain. [Rieder, Mark J.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Hall, Jennifer; Welch, Cullan] Univ Minnesota, Dept Med, Lillehei Heart Inst, Minneapolis, MN 55455 USA. [Abecasis, Goncalo] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Tai, E. Shyong] Singapore Gen Hosp, Dept Endocrinol, Singapore 0316, Singapore. [Arnett, Donna K.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr, Dietary Assessment & Epidemiol Res Program, Boston, MA 02111 USA. [Tucker, Katherine L.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Hedner, Thomas; Wahlstrand, Bjoern] Sahlgrens Acad, Dept Clin Pharmacol, Gothenburg, Sweden. [Tuomi, Tiinaimaija; Taskinen, Marja-Riitta; Groop, Leif] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland. [Tuomi, Tiinaimaija; Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland. [Hughes, Thomas E.] Novartis Inst BioMed Res, Cambridge, MA USA. [Berglund, Goran] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Peltonen, Leena] Natl Publ Hlth Inst, Biomedicum, Dept Mol Med, Helsinki, Finland. [Vartiainen, Erkki; Jousilahti, Pekka; Havulinna, Aki S.; Salomaa, Veikko] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Ctr Human Genet Res, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Cardiovasc Dis Prevent Ctr,Cardiol Div, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. RP Orho-Melander, M (reprint author), Lund Univ, Malmo Gen Hosp, Clin Res Ctr, Dept Clin Sci, S-21401 Malmo, Sweden. EM marju.orho-melander@med.lu.se RI Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; Tucker, Katherine/A-4545-2010; de Bakker, Paul/B-8730-2009; OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Perez Martinez, Pablo/0000-0001-7716-8117; Abecasis, Goncalo/0000-0003-1509-1825; Tucker, Katherine/0000-0001-7640-662X; Tuomi, Tiinamaija/0000-0002-8306-6202; Ordovas, Jose/0000-0002-7581-5680; Tai, E Shyong/0000-0003-2929-8966 FU Lund University; Novo Nordic Foundations; Swedish Medical Research Council; Swedish Heart and Lung Foundation; Region Skane; Medical Faculty of Lund University; Malmo University Hospital; Albert Pahlsson Research Foundation; Crafoord Foundation; Swedish Medical Society; Ernhold Lundstroms Research Foundation; Mossfelt Foundation; King Gustav V and Queen Victoria Foundation; NIH [R01-NS-053646, P01-AG-023394-03, 53-K06-5-10, K23-HL-083102, PO1-GM-32165]; Sigrid Juselius Foundation; U.S. Department of Agriculture [58-1950-9-001]; NIH-NHLBI [U01-HL-72524, HL-54776]; Finnish Heart Foundation; Clinical Research Institute, Helsinki University Central Hospital; Finnish Diabetes Research Foundation; Folkhalsan Research Foundation; Knut and Alice Wallenberg Stiftelse; Clinical Research Institute HUCH; Swedish Research Council; Doris Duke Charitable Foundation; University of Washington School of Pharmacy; Abbott; Allergan; Amgen; Bend Research; Bristol-Myers Squibb; Eli Lilly; Johnson Johnson; Merck; Roche; Pfizer FX M.O.-M. is supported by the Diabetes program at the Lund University and Novo Nordic Foundations, the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Region Skane, the Medical Faculty of Lund University, the Malmo University Hospital, the Albert Pahlsson Research Foundation, and the Crafoord Foundation. O.M. is supported by the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Region Skane, the Medical Faculty of Lund University, the Malmo University Hospital, the Albert Pahlsson Research Foundation, the Crafoord Foundation, the Swedish Medical Society, the Ernhold Lundstroms Research Foundation, the Mossfelt Foundation, and the King Gustav V and Queen Victoria Foundation. M.J.R. is supported by NIH Grant R01-NS-053646. V.L. is supported by the Sigrid Juselius Foundation. K.L.T. is supported by U.S. Department of Agriculture Contract 58-1950-9-001, NIH Grant P01-AG-023394-03, NIH Contract 53-K06-5-10, and NIH-NHLBI Grants U01-HL-72524 and HL-54776. M.-R.T. is supported by the Sigrid Juselius Foundation, the Finnish Heart Foundation, and the Clinical Research Institute, Helsinki University Central Hospital. L.G. is supported by the Sigrid Juselius Foundation, the Finnish Diabetes Research Foundation, The Folkhalsan Research Foundation, Knut and Alice Wallenberg Stiftelse, the Clinical Research Institute HUCH, and a Linne grant from the Swedish Research Council. J.M.O. is supported by U.S. Department of Agriculture Contract 58-1950-9-001, NIH Grant P01-AG-023394-03, NIH Contract 53-K06-5-10, and NIH-NHLBI grants U01-HL-72524 and HL-54776. S.K. is supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award, a charitable gift from the Fannie E. Rippel Foundation, and NIH Grant K23-HL-083102. The University of Washington School of Pharmacy Human Liver Bank is supported in part by NIH Grant PO1-GM-32165. Liver expression studies are supported in part by the University of Washington School of Pharmacy Drug Metabolism, Transport and Pharmacogenomics Research program (funded by unrestricted gifts from Abbott, Allergan, Amgen, Bend Research, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, Roche, and Pfizer). We thank Dr. Helen Hobbs and Dr. Jonathan Cohen for their contribution of the Dallas Heart Study data and the Donald W. Reynolds Foundation for its support of the Dallas Heart Study. We are indebted to the staff and participants of all of the study populations for their important contributions. We thank Malin Svensson for technical assistance in Malmo and the RSKC2 (Region Skania) genotyping facility for help with genotyping of the NORDIL sample. NR 40 TC 164 Z9 168 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 3112 EP 3121 DI 10.2337/db08-0516 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800032 PM 18678614 ER PT J AU Yoshida, M Jacques, PF Meigs, JB Saltzman, E Shea, MK Gundberg, C Dawson-Hughes, B Dallal, G Booth, SL AF Yoshida, Makiko Jacques, Paul F. Meigs, James B. Saltzman, Edward Shea, M. Kyla Gundberg, Caren Dawson-Hughes, Bess Dallal, Gerard Booth, Sarah L. TI Effect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women SO DIABETES CARE LA English DT Article ID YOUNG MALE-VOLUNTEERS; GLUCOSE-TOLERANCE; BETA-CELL; MENAQUINONE-4; PHYLLOQUINONE; OSTEOCALCIN; DIETARY; OBESITY; HEALTH AB OBJECTIVE - Vitamin K has a potentially beneficial role in insulin resistance, but evidence is limited in humans. We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women. RESEARCH DESIGN AND METHODS - This was an ancillary study of a 36-month, randomized, double-blind, controlled trial designed to assess the impact of Supplementation with 500 mu g/day phylloquinone on bone loss. Study participants were older nondiabetic men and women (n = 355; aged 60-80 years; 60% women). The primary outcome of this study was insulin resistance as measured by homeostasis model assessment (HOMA-IR) at 36 months. Fasting plasma insulin and glucose were examined as the secondary outcomes. RESULTS - The effect of 36-month vitamin K supplementation on HOMA-IR differed by sex (sex X treatment interaction P = 0.02). HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group versus the men in the control group (P = 0.01) after adjustment for baseline HOMA-IR, BMI, and body weight change. There were no statistically significant differences in outcome measures between intervention groups in women. CONCLUSIONS - Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men. C1 [Yoshida, Makiko; Jacques, Paul F.; Saltzman, Edward; Shea, M. Kyla; Dawson-Hughes, Bess; Dallal, Gerard; Booth, Sarah L.] Tufts Univ, Human Nutr Res Ctr, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Gundberg, Caren] Yale Univ, Sch Med, Dept Orthopaed, New Haven, CT USA. RP Booth, SL (reprint author), Tufts Univ, Human Nutr Res Ctr, Jean Mayer US Dept Agr, Boston, MA 02111 USA. EM sarah.booth@tufts.edu FU U.S. Department of Agriculture; Agricultural Research Service [58-1950-7-707]; National Institutes of Health [AG14759, HL69272, TH32, HL69772-01A1, AR38460]; Ministry of Education, Culture, Sports and Technology of Japan; American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140] FX This work was supported by the U.S. Department of Agriculture, Agricultural Research Service, under Cooperative Agreement 58-1950-7-707, the National Institutes of Health (AG14759, HL69272, TH32 HL69772-01A1, and AR38460), and the American Heart Association (0515605T). M.Y. was supported by a Graduate Student Scholarship from the Ministry of Education, Culture, Sports and Technology of Japan. J.B.M. was supported by a Career Development Award from the American Diabetes Association and by National Institute of Diabetes and Digestive and Kidney Diseases Grant K24 DK080140. Hermes Arznemittel, Munich, Germany, generously donated the supplements used for this study.; The authors express their appreciation to James Peterson, Nancy Palermo, Anne Charette, Molly Damon, the staff of the Metabolic Research Unit and Nutrition Evaluation Laboratory, and all the stud), participants for their invaluable contribution to this study. NR 23 TC 53 Z9 55 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 NOV PY 2008 VL 31 IS 11 BP 2092 EP 2096 DI 10.2337/dc08-1204 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PT UT WOS:000260565000003 PM 18697901 ER PT J AU Martin, AL Lumber, T Compton, T Ernst, K Haas, L Regan-Klich, J Letassy, N McKnight, KA Nelson, JB Seley, JJ Toth, JA Mensing, C AF Martin, Annette Lenzi Lumber, Terry Compton, Terry Ernst, Kristina Haas, Linda Regan-Klich, Janet Letassy, Nancy McKnight, Karen A. Nelson, Joseph B. Seley, Jane Jeffrie Toth, Judith A. Mensing, Carole TI Insights and Trends in Diabetes Education Results of the 2008 AADE National Diabetes Education Practice Survey SO DIABETES EDUCATOR LA English DT Article AB Purpose The purpose of this study is to describe current diabetes education practice and specific interventions and responsibilities of diabetes educators in the United States. Methods The 2008 National Practice Survey (NPS) instrument consisted of 53 items addressing diabetes education program structure, processes and interventions, outcomes and quality improvement activities, and the chronic care model. The survey was hosted online for American Association of Diabetes Educators (AADE) members. Participants totaled 2447 members, constituting a 25% return rate. Data from the 2008 NPS were analyzed and compared with results from previous surveys. Results Nearly two-thirds of respondents in 2008 provided diabetes education in a single location, most commonly in a clinical outpatient/managed care setting (39%). Most programs provided comprehensive services. Managers noted that 42% of their programs were either cost/revenue neutral or profitable. Programs varied in types of services, number of patient visits, team member functions, time spent on services, and instructional methods used. At least 50% of managers said their programs report outcome data, and 88% participate in quality/performance improvement activities. Nearly two-thirds of respondents were unfamiliar with the AADE-adopted chronic care model. Conclusions Many 2008 NPS results concur with those obtained in 2005 through 2007. Areas of variability among programs suggest a need for standardized interventions and practice guidelines. Educators are encouraged to report outcomes to elucidate the contributions of their programs to patient care. AADE can use the results and comparative data obtained from the 2008 survey when developing practice, research, and advocacy activities. C1 [Lumber, Terry] Inova Diabet Ctr, Fairfax, VA 22301 USA. [Martin, Annette Lenzi] Lenzi Martin Commun Inc, Chicago, IL USA. [Compton, Terry] Southeastern Univ, Sch Nursing, Hammond, LA USA. [Ernst, Kristina] Div Diabet Translat, Atlanta, GA USA. [Haas, Linda] VA Puget Sound Seattle Div, Seattle, WA USA. [Regan-Klich, Janet] Univ Chicago, Chicago, IL 60637 USA. [Letassy, Nancy] Univ Oklahoma, Coll Pharm, Edmond, OK USA. [McKnight, Karen A.] St Joseph Healthcare Diabet Treatment Ctr, Lexington, KY USA. [Seley, Jane Jeffrie] New York Presbyterian WC, New York, NY USA. [Toth, Judith A.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Mensing, Carole] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Lumber, T (reprint author), Inova Diabet Ctr, 2700 Prosper Ave,Suite 100, Fairfax, VA 22301 USA. EM terry.lumber@inova.org RI Seley, Jane/D-1708-2013 NR 7 TC 7 Z9 7 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD NOV-DEC PY 2008 VL 34 IS 6 BP 970 EP 986 DI 10.1177/0145721708327286 PG 11 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 384FP UT WOS:000261731000005 PM 19075080 ER PT J AU Kahn, SE Carr, DB Faulenbach, MV Utzschneider, KM AF Kahn, S. E. Carr, D. B. Faulenbach, M. V. Utzschneider, K. M. TI An examination of P-cell function measures and their potential use for estimating beta-cell mass SO DIABETES OBESITY & METABOLISM LA English DT Article DE arginine. C-peptide; diabetes mellitus; glucose potentiation; impaired glucose tolerance; insulin; intravenous glucose; obesity; OGTT ID DEPENDENT DIABETES-MELLITUS; INDUCED INSULIN-RESISTANCE; DISPROPORTIONATELY ELEVATED PROINSULIN; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; STREPTOZOCIN-TREATED BABOONS; IMPAIRED GLUCOSE-TOLERANCE; POLYCYSTIC-OVARY-SYNDROME; LIFE-STYLE INTERVENTION; PANCREATIC B-CELL; SECRETORY CAPACITY AB A characteristic and dominant feature of type 2 diabetes is a reduction in P-cell function that is associated with a decrease in P-Cell volume. A decline in the first-phase insulin response following intravenous glucose administration can be demonstrated as the fasting glucose concentration increases. This response is completely absent before the glucose threshold that defines diabetes has been reached and at a time when P-cells are clearly still present, implying that a functional beta-cell lesion has to exist independent of beta-cell loss. Surgical or chemical reductions of tip to 65% of beta-cell volume demonstrate that functional adaptation of the normal P-cell prevents a rise in fasting glucose or reduction in first-phase insulin response. However, the ability Of glucose to potentiate the beta-cell's response to non-glucose secretagogues is reduced and is more closely associated with the reduction in beta-cell volume. The future, in terms of prevention and treatment of type 2 diabetes, lies in the ability to prevent and revert both beta-cell loss and dysfunction. However, until beta-cell volume can be quantified reliably and non-invasively, we will need to rely on the ability of glucose, to potentiate insulin release as the best Surrogate estimate of the number of beta-cells. C1 [Kahn, S. E.; Faulenbach, M. V.; Utzschneider, K. M.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Carr, D. B.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 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; American Diabetes Association Distinguished Clinical Scientist Award; Swiss National Foundation FX This study was supported in part by the, Department of Veterans Affairs. S. E. K. is the recipient of an American Diabetes Association Distinguished Clinical Scientist Award. M. V. F. is supported by Foods from the Swiss National Foundation. NR 81 TC 25 Z9 26 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD NOV PY 2008 VL 10 SU 4 BP 63 EP 76 DI 10.1111/j.1463-1326.2008.00945.x PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 398IR UT WOS:000262726300008 PM 18834434 ER PT J AU Medarova, Z Moore, A AF Medarova, Z. Moore, A. TI Non-invasive detection of transplanted pancreatic islets SO DIABETES OBESITY & METABOLISM LA English DT Article DE contrast agent; in vivo imaging; islet labelling; islet transplantation; magnetic resonance imaging ID POSITRON-EMISSION-TOMOGRAPHY; TYPE-1 DIABETES-MELLITUS; GRAFT-SURVIVAL; HER-2/NEU RECEPTOR; INSULIN-SECRETION; EDMONTON PROTOCOL; HEPATIC STEATOSIS; MOUSE MODEL; NUDE-MICE; HYPERGLYCEMIA AB Type 1 diabetes (insulin-dependent, IDDM) results in immune-mediated destruction of pancreatic beta cells, which leads to a deficiency in insulin secretion and as a result, to hyperglycaemia. Keeping blood glucose levels under tight control represents the most effective way either to prevent the onset or to reduce the progression of the chronic complications of IDDM. At present, pancreatic islet transplantation is emerging as the most promising clinical modality. which call stop diabete's progression without increasing the incidence of hypoglycaemic events. Although early results of clinical trials using the Edmonton Protocol all its variations are very encouraging, it is still unclear how long the islets will survive and how often the transplantation procedure. will be successful. In order to monitor transplantation efficiency and graft Survival, reliable non-invasive unaging methods are needed. If such methods are introduced clinically. essential information regarding the location, function all viability of transplanted islets call be obtained repeatedl'y and non-invasively. This review will focus on the latest advancements in the field of in vivo imaging of islet transplantation and describe various islet labelling and imaging techniques. In addition. we will critically look into limitations and obstacles currently present on the way to successful clinical implementation of this approach. C1 [Medarova, Z.; Moore, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Program,MIT,Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Program,MIT,Athinoula A Martinos Ctr, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.harvard.edu FU National Institutes of Health [RO1KO72137, RO1DK078615] FX This work was Supported in part by National Institutes of Health grants (RO1KO72137 and RO1DK078615) to A.M. NR 69 TC 19 Z9 19 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD NOV PY 2008 VL 10 BP 88 EP 97 DI 10.1111/j.1463-1326.2008.00942.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 398IR UT WOS:000262726300010 PM 18834436 ER PT J AU Hinault, C Hu, J Maier, BF Mirmira, RG Kulkarni, RN AF Hinault, C. Hu, J. Maier, B. F. Mirmira, R. G. Kulkarni, R. N. TI Differential expression of cell cycle proteins during ageing of pancreatic islet cells SO DIABETES OBESITY & METABOLISM LA English DT Article DE ageing; beta-cells; cell cycle; diabetes; islets ID NUTRITION EXAMINATION SURVEY; INSULIN GENE-EXPRESSION; 3RD NATIONAL-HEALTH; BETA-CELL; RETINOBLASTOMA PROTEIN; DEPENDENT KINASE-4; PRIMARY MECHANISM; ENDOCRINE TUMORS; CDK INHIBITORS; MICE DEFICIENT AB One of the major challenges for developmental biologists and investigators in the field of diabetes over the last few decades has been to dissect the origin of pancreatic endocrine cells and to accurately understand the mechanisms that regulate islet cell regeneration. While significant advances have been made recently. there Continues to he a paucity of knowledge regarding the growth factor signalling, pathways that directly regulate the proteins involved in islet cell cycle control. We will discuss recent work in these areas and provide insights from our studies into age-dependent alterations in the expression of growth factor signalling proteins and cell cycle proteins in islet cells. C1 [Hinault, C.; Hu, J.; Kulkarni, R. N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Hinault, C.; Hu, J.; Kulkarni, R. N.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Maier, B. F.; Mirmira, R. G.] Indiana Univ, Sch Med, Dept Pediat, Wells Ctr Pediat Res, Indianapolis, IN 46202 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu OI hinault, charlotte/0000-0002-3588-039X FU National Institute of Health [RO1 DK67536]; [RO1 DK60581]; [1RL9EB008539-01] FX We thank the organizers of the International Group on Insulin Secretion for the opportunity to share these data, Lindsay Huse for excellent assistance with preparation of the manuscript and Heidi Scrable, PhD (U Virginia, Charlottesville) for antibodies. This work was supported in part by National Institute of Health RO1 DK67536 to R. N. K. and NIH RO1 DK60581 to R. G. M. An NIH training grant (1RL9EB008539-01) [SysCODE) supported C. H. NR 70 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD NOV PY 2008 VL 10 BP 136 EP 146 DI 10.1111/j.1463-1326.2008.00947.x PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 398IR UT WOS:000262726300015 PM 18834441 ER PT J AU Cowley, MS Boyko, EJ Shofer, JB Ahroni, JH Ledoux, WR AF Cowley, Matthew S. Boyko, Edward J. Shofer, Jane B. Ahroni, Jessie H. Ledoux, William R. TI Foot ulcer risk and location in relation to prospective clinical assessment of foot shape and mobility among persons with diabetes SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetic foot ulcer; Foot deformity; Foot structure; Neuropathy ID LOWER-EXTREMITY ULCERS; PLANTAR PRESSURES; TOE DEFORMITY; NEUROPATHY; PREDICTORS; MELLITUS; WALKING AB Aims: We assessed baseline clinical foot shape for 2939 feet of diabetic subjects who were monitored prospectively for foot ulceration. Methods: Assessments included hammer/claw toes, hallux valgus, hallux limitus, prominent metatarsal heads, bony prominences, Charcot deformity, plantar callus, foot type, muscle atrophy, ankle and hallux mobility, and neuropathy. Risk factors were linked to ulcer occurrence and location via a Cox proportional hazards model. Results: Hammer/claw toes (hazard ratio [HR] (95% confidence interval [CI]) = 1.43 (1.06, 1.94) p = 0.02), marked hammer/claw toes (HR = 1.77 (1.18, 2.66) p = 0.006), bony prominences (HR = 1.38 (1.02, 1.88), p = 0.04), and foot type (Charcot or drop foot vs. neutrally aligned) (HR = 2.34 (1.33, 4.10), p = 0.003) were significant risk factors for ulceration adjusting for age, body mass index, insulin medication, ulcer history and amputation history. With adjustment for neuropathy only hammer/claw toes (HR = 1.40 (1.03, 1.90), p = 0.03) and foot type (HR = 1.76 (1.04, 3.04), p = 0.05) were significantly related to ulceration. However, there was no relationship between ulcer location and foot deformity. Conclusions: Certain foot deformities were predictive of ulceration, although there was no relationship between clinical foot deformity and ulcer location. Published by Elsevier Ireland Ltd. C1 [Cowley, Matthew S.; Shofer, Jane B.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Dept Vet Affairs, Seattle, WA 98108 USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Boyko, Edward J.] Univ Washington, Dept Gen Internal Med, Seattle, WA 98195 USA. [Ahroni, Jessie H.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Ahroni, Jessie H.] NW Weight Loss Surg, Everett, WA 98208 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU Department of Veterans Affairs (VA) Rehabilitation Research and Development [A2661C, A318-5RC]; Seattle VA Epidemiologic Research and Information Center (ERIC) [EPC 97-010]; The University of Washington DERC (NIH NIDDK) [P30 DK-17047] FX This research was supported by the Department of Veterans Affairs (VA) Rehabilitation Research and Development grants A2661C and A318-5RC, the Seattle VA Epidemiologic Research and Information Center (ERIC) EPC 97-010 and The University of Washington DERC (NIH NIDDK grant P30 DK-17047). NR 24 TC 23 Z9 23 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV PY 2008 VL 82 IS 2 BP 226 EP 232 DI 10.1016/j.diabres.2008.07.025 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 382HU UT WOS:000261597600012 PM 18829126 ER PT J AU Nansel, TR Weisberg-Benchell, J Wysocki, T Laffel, L Anderson, B AF Nansel, T. R. Weisberg-Benchell, J. Wysocki, T. Laffel, L. Anderson, B. CA Steering Comm Family Management Di TI Quality of life in children with Type 1 diabetes: a comparison of general and diabetes-specific measures and support for a unitary diabetes quality-of-life construct SO DIABETIC MEDICINE LA English DT Article DE children; measurement; quality of life; Type 1 diabetes ID INSULIN PUMP THERAPY; METABOLIC-CONTROL; SELF-MANAGEMENT; ADOLESCENTS; PARENTS AB Aims To assess the factor structure of the Pediatric Quality of Life Inventory (PedsQL) Diabetes Module and to compare the PedsQL general and diabetes-specific quality of life (QOL) measures regarding psychometric properties and relations to relevant outcomes. Methods The instruments were completed by 447 children age 9 to 15.5 years with Type 1 diabetes > 1 year from four US paediatric diabetes clinics; parents completed the parallel parent-proxy measures. Principal components factor analysis was used to examine the factor structure of the PedsQL diabetes module. Analyses of the generic and diabetes QOL measures included psychometric properties, parent-child correlations and correlations with depression, adherence and glycated haemoglobin (HbA(1c)). Results The factor structure of the PedsQL diabetes module did not support the original five subscales. Both one- and two-factor models were supported; however, parallel parent and child subscales did not emerge. While the generic and diabetes-specific measures of QOL were moderately to highly correlated with each other, the constructs were differentially associated with relevant diabetes outcomes. Generic QOL was more highly associated with depression than diabetes QOL. Conversely, diabetes QOL was more highly associated with adherence and HbA(1c), although this was seen to a greater extent for parent-proxy report than for child report. Conclusions Factor analysis of the PedsQL diabetes module supports the use of a total diabetes QOL score. Findings regarding the associations of the generic and diabetes modules with diabetes outcomes underscore the unique contribution provided by both generic and diabetes QOL. C1 [Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, DESPR, NIH,DHHS, Bethesda, MD USA. [Weisberg-Benchell, J.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Wysocki, T.] Nemours Childrens Hosp, Jacksonville, FL USA. [Laffel, L.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Anderson, B.] Baylor Coll Med, Houston, TX 77030 USA. RP Nansel, TR (reprint author), NICHD, DESPR, PRB, 6100 Execut Blvd,Rm 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS [Z01 HD008741-06]; NICHD NIH HHS [N01-HD-3-3360, N01-HD-4-3361, N01-HD-4-3364] NR 24 TC 32 Z9 33 U1 4 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD NOV PY 2008 VL 25 IS 11 BP 1316 EP 1323 DI 10.1111/j.1464-5491.2008.02574.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367BT UT WOS:000260528200009 PM 19046222 ER PT J AU Brugge, WR AF Brugge, W. R. TI Management and outcomes of pancreatic cystic lesions SO DIGESTIVE AND LIVER DISEASE LA English DT Article ID PAPILLARY MUCINOUS TUMOR; AGGRESSIVE SURGICAL APPROACH; COST-BENEFIT-ANALYSIS; SIMPLE RENAL CYSTS; TERM-FOLLOW-UP; ENDOSCOPIC ULTRASOUND; PREOPERATIVE EVALUATION; ETHANOL INJECTION; NATURAL-HISTORY; HEPATIC CYSTS AB The management of pancreatic cystic lesions offers a challenge to clinicians. Mucinous cystic lesions pose a low risk of the development of neoplasia that must be taken into account in long-term management. Although the natural history has not been well defined, it is likely that malignant change in the mucinous epithelium takes place over years, very similar to what is observed with Barrett's esophagus. The traditional therapy of mucinous cystic lesions has been surgical resection. Lesions in the head of the pancreas will require a Whipple resection whereas tail lesions are managed with a distal pancreatectomy and splenectomy. In patients at high fisk for surgical resection, the risk/benefit ratio may be excessively high, not supporting the use of resection therapy. Ethanol ablation therapy has been thoroughly studied in hepatic, renal, and thyroid cysts. Epithelial ablation with ethanol appears to be highly effective and relatively safe. Recently, ethanol ablation has been evaluated in pancreatic Cystic neoplasms. In macrocystic lesions between I and 5 cm, ethanol lavage will result in epithelial ablation and cyst resolution in a high percentage of patients. Pancreatitis is rarely observed clinically and is not present in resection specimens. A randomised prospective clinical trial is currently underway. (C) 2008 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. C1 Massachusetts Gen Hosp, GI Unit Blake 4, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit Blake 4, 55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org NR 47 TC 17 Z9 18 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD NOV PY 2008 VL 40 IS 11 BP 854 EP 859 DI 10.1016/j.dld.2008.03.023 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368BI UT WOS:000260595900004 PM 18502709 ER PT J AU Leung, FW AF Leung, Felix W. TI Water-Related Techniques for Performance of Colonoscopy SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Colonoscopy; Water infusion AB Background Passage through difficult colonic segments, cecal intubation rate, time to reach the cecum, procedure-related discomfort, and medication requirement are important outcome measures of a colonoscopic examination. Several techniques of water infusion to aid insertion have been described. Raising awareness of these simple inexpensive methods may help to enhance colonoscopists' performance. Aim To review water-related methods that facilitated colonoscope insertion. Method A literature search (Medline, PubMed) was conducted using the following terms: sigmoidoscopy, colonoscopy, and water infusion, irrigation, or loading. The effects of water infusion in sedated and unsedated patients are tabulated and discussed. Results Five reports described the use of water infusion in conjunction with usual air insufflation. Enhanced cecal intubation, decreased time to reach the cecum, and attenuated abdominal discomfort were reported. Dose of medication used for sedation was not reduced. The sixth report described a novel method of water infusion in lieu of air insufflation during insertion. When patients accepted sedation on demand, the novel method permitted 52% to complete colonoscopy without sedation. Conclusion Warm water infusion as an adjunct to usual air insufflation enhances colonoscopy outcome. Randomized controlled trials comparing the novel method with usual air insufflation deserve to be considered. C1 [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gastroenterol, Los Angeles, CA 90024 USA. [Leung, Felix W.] VA Greater Los Angels Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Div Gastroenterol, North Hills, CA 91343 USA. RP Leung, FW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gastroenterol, Los Angeles, CA 90024 USA. EM felix.leung@va.gov FU Affairs Medical Research Funds; American Society of Gastrointestinal Endoscopy FX This study was supported in part by Veterans Affairs Medical Research Funds and in part by the American Society of Gastrointestinal Endoscopy Career Development Award ( F. W. L., 1985). NR 6 TC 24 Z9 26 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2008 VL 53 IS 11 BP 2847 EP 2850 DI 10.1007/s10620-008-0259-1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 363EG UT WOS:000260250000002 PM 18461455 ER PT J AU Leung, FW AF Leung, Felix W. TI Promoting Informed Choice of Unsedated Colonoscopy: Patient-Centered Care for a Subgroup of U. S. Veterans SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Informed choice; Unsedated colonoscopy; Patient-centered care; US veterans ID SCREENING COLONOSCOPY; FLEXIBLE SIGMOIDOSCOPY; ASSISTED COLONOSCOPY; SEDATION; ENDOSCOPY; COMPLICATIONS; OPTIONS; CANCER; TRIAL AB Background In the United States, colonoscopy is usually performed under sedation. In practice, 2.3-7% actually requested unsedated colonoscopy and 1.4% received it because of no escorts. Efforts to increase usage would likely require increased patient counseling and education. Aim We tested the hypothesis that knowledge conveyed by education-a key attribute of patient-centered care-is associated with acceptance of the "non-usual" option. Methods After patients underwent discussions and expressed acceptance of sedated colonoscopy, the pros and cons of and local experience with unsedated colonoscopy were added. The patients who changed from accepting sedated to unsedated colonoscopy and outcomes of their examinations were recorded. Results From January to November 2006, 49 of 176 consecutive patients (28%) changed their choice from sedated to unsedated colonoscopy after being informed of the latter. Forty-eight had satisfactory bowel preparation. Cecal intubation rate was 93.7% (45 of 48). Thirty-six reported good experience and 43, likely to repeat. Cecal intubation, withdrawal, and discharge times were 23.0 +/- 1.4 min, 15.0 +/- 1.0 min, and 5.0 +/- 0.5 min, respectively (n = 45). Ability to communicate with the colonoscopist during and after the examination was the most frequently ranked reason for choosing unsedated colonoscopy. Conclusion Our uncontrolled, non-randomized, single-site observational data revealed that for selected veterans, acceptance of unsedated colonoscopy coincides with knowledge of the option dispensed by patient counseling and education. C1 [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Div Gastroenterol, North Hills, CA 91343 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gastroenterol, Los Angeles, CA 90024 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Div Gastroenterol, 111G,16111 Plummer St, North Hills, CA 91343 USA. EM felix.leung@va.gov FU Veterans Affairs Medical Research; ASGE FX This work was supported in part by Veterans Affairs Medical Research Funds and in part by ASGE Career Development Award (FWL 1985). NR 34 TC 9 Z9 11 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2008 VL 53 IS 11 BP 2955 EP 2959 DI 10.1007/s10620-008-0253-7 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 363EG UT WOS:000260250000017 PM 18461456 ER PT J AU Mu, Y Klamerus, MM Miller, TM Rohan, LC Graham, SH Poloyac, SM AF Mu, Ying Klamerus, Megan M. Miller, Tricia M. Rohan, Lisa C. Graham, Steven H. Poloyac, Samuel M. TI Intravenous Formulation of N-Hydroxy-N '-(4-n-butyl-2-methylphenyl) formamidine (HET0016) for Inhibition of Rat Brain 20-Hydroxyeicosatetraenoic Acid Formation SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ARACHIDONIC-ACID; SELECTIVE INHIBITOR; 20-HETE; CYTOCHROME-P450; EXPRESSION; 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN; DERIVATIVES; ISCHEMIA; SYNTHASE; INJURY AB N-Hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine (HET0016) is a potent inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation by specific cytochrome P450 isoforms. Previous studies have demonstrated that administration of HET0016 inhibits brain formation of 20-HETE and reduces brain damage in a rat model of thromboembolic stroke. Delineation of the dose, concentration, and neuroprotective effect relationship of HET0016 has been hampered by the relative insolubility of HET0016 in aqueous solutions and the lack of information concerning the mechanism and duration of HET0016 inhibition of brain 20-HETE formation. Therefore, it was the purpose of this study to develop a water-soluble formulation of HET0016 suitable for intravenous (i.v.) administration and to determine the time course and mechanism of brain 20-HETE inhibition after in vivo dosing. In this study we report that HET0016 is a noncompetitive inhibitor of rat brain 20-HETE formation, which demonstrates a tissue concentration range for brain inhibition. In addition, we demonstrate that complexation of HET0016 with hydroxypropyl-beta-cyclodextrin results in increased aqueous solubility of HET0016 from 34.2 +/- 31.2 to 452.7 +/- 63.3 mu g/ml. Administration of the complex as a single HET0016 i.v. dose (1 mg/kg) rapidly reduced rat brain 20-HETE concentrations from 289 to 91 pmol/g. Collectively, these data demonstrate that the i. v. formulation of HET0016 rapidly penetrates the rat brain and significantly inhibits 20-HETE tissue concentrations. These results will enable future studies to determine biopharmaceutics of HET0016 for inhibition of 20-HETE after cerebral ischemia. C1 [Mu, Ying; Klamerus, Megan M.; Miller, Tricia M.; Rohan, Lisa C.; Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Rohan, Lisa C.] Magee Womens Res Inst, Pittsburgh, PA USA. [Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Graham, Steven H.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Poloyac, SM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 807 Salk Hall, Pittsburgh, PA 15261 USA. EM poloyac@pitt.edu FU National Institutes of Health [NINDS R01NS052315, NCRR S10RR023461]; NCRR FX We acknowledge National Institutes of Health NINDS R01NS052315 (S. M. P.) and NCRR S10RR023461 (S. M. P.) for support of this work. We also acknowledge the Pharsight Academic License granted for use in the pharmacokinetic analyses. Y.M. and M. M. K. contributed equally to this work. NR 25 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 2008 VL 36 IS 11 BP 2324 EP 2330 DI 10.1124/dmd.108.023150 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 361MP UT WOS:000260132100022 PM 18725506 ER PT J AU Norris, AW Hirshman, MF Yao, JR Jessen, N Musi, N Chen, LH Sivitz, WI Goodyear, LJ Kahn, CR AF Norris, Andrew W. Hirshman, Michael F. Yao, Jianrong Jessen, Niels Musi, Nicolas Chen, Lihong Sivitz, William I. Goodyear, Laurie J. Kahn, C. Ronald TI Endogenous Peroxisome Proliferator-Activated Receptor-gamma Augments Fatty Acid Uptake in Oxidative Muscle SO ENDOCRINOLOGY LA English DT Article ID TYPE-2 DIABETIC SUBJECTS; RAT SKELETAL-MUSCLE; INDUCED INSULIN-RESISTANCE; ALPHA PPAR-ALPHA; PROTEIN-KINASE; GENE-EXPRESSION; ADIPOSE-TISSUE; ROSIGLITAZONE TREATMENT; IN-VIVO; UNCOUPLING PROTEIN-3 AB In the setting of insulin resistance, agonists of peroxisome proliferator-activated receptor (PPAR)-gamma restore insulin action in muscle and promote lipid redistribution. Mice with muscle-specific knockout of PPAR gamma (MuPPAR gamma KO) develop excess adiposity, despite reduced food intake and normal glucose disposal in muscle. To understand the relation between muscle PPAR gamma and lipid accumulation, we studied the fuel energetics of MuPPAR gamma KO mice. Compared with controls, MuPPAR gamma KO mice exhibited significantly increased ambulatory activity, muscle mitochondrial uncoupling, and respiratory quotient. Fitting with this latter finding, MuPPAR gamma KO animals compared with control siblings exhibited a 25% reduction in the uptake of the fatty acid tracer 2-bromo-palmitate (P < 0.05) and a 13% increase in serum nonesterified fatty acids (P = 0.05). These abnormalities were associated with no change in AMP kinase (AMPK) phosphorylation, AMPK activity, or phosphorylation of acetyl-CoA carboxylase in muscle and occurred despite increased expression of fatty acid transport protein 1. Palmitate oxidation was not significantly altered in MuPPAR gamma KO mice despite the increased expression of several genes promoting lipid oxidation. These data demonstrate that PPAR gamma, even in the absence of exogenous activators, is required for normal rates of fatty acid uptake in oxidative skeletal muscle via mechanisms independent of AMPK and fatty acid transport protein 1. Thus, when PPAR gamma activity in muscle is absent or reduced, there will be decreased fatty acid disposal leading to diminished energy utilization and ultimately adiposity. (Endocrinology 149: 5374-5383, 2008) C1 [Norris, Andrew W.; Yao, Jianrong] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. [Sivitz, William I.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Hirshman, Michael F.; Jessen, Niels; Musi, Nicolas; Chen, Lihong; Goodyear, Laurie J.; Kahn, C. Ronald] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Norris, AW (reprint author), Univ Iowa, Dept Pediat, Carver Coll Med, 4-532 BSB, Iowa City, IA 52242 USA. EM andrew-norris@uiowa.edu RI Jessen, Niels/E-1731-2011 FU National Institutes of Health [K08-DK064906, R01-AR45670, R01-DK068626]; Veterans Affairs Medical Research; Joslin Diabetes Center Diabetes and Endocrinology Research Center [DK25295, R01-DK60837, DK36836] FX This work was supported by National Institutes of Health Grants K08-DK064906 (to A.W.N.), R01-AR45670 and R01-DK068626 (to L.J.G.), Veterans Affairs Medical Research Funds and Grant DK25295 (to W.I.S.), Grant R01-DK60837 (to C.R.K.), and Grant DK36836 to the Joslin Diabetes Center Diabetes and Endocrinology Research Center. NR 75 TC 6 Z9 7 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2008 VL 149 IS 11 BP 5374 EP 5383 DI 10.1210/en.2008-0100 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 362JM UT WOS:000260194000008 PM 18653710 ER PT J AU Zhao, WD Pan, JP Wang, XL Wu, Y Bauman, WA Cardozo, CP AF Zhao, Weidong Pan, Jiangping Wang, Xiaolei Wu, Yong Bauman, William A. Cardozo, Christopher P. TI Expression of the Muscle Atrophy Factor Muscle Atrophy F-Box Is Suppressed by Testosterone SO ENDOCRINOLOGY LA English DT Article ID DEPENDENT PROTEOLYTIC SYSTEM; FOXO TRANSCRIPTION FACTORS; STEROID-HORMONE RECEPTORS; ANDROGEN RECEPTOR; SKELETAL-MUSCLE; UBIQUITIN LIGASES; DNA-BINDING; DENERVATION ATROPHY; GENE-EXPRESSION; DEGRADATION AB The ubiquitin ligase muscle atrophy F-box (MAFbx; also called atrogin-1) is thought to play important roles in muscle loss. Conversely, testosterone reduces atrophy from glucocorticoids or denervation associated with repression of MAFbx. To characterize mechanisms of such repression, the effects of testosterone on MAFbx expression in C2C12 cells were tested. Testosterone reduced MAFbx mRNA levels as well as expression of a reporter gene under the control of 3.1 kb of the human MAFbx promoter. Repression required the androgen receptor (AR) as well as sequences within the first 208 bases upstream of the first codon of the MAFbx gene. This sequence is downstream of known forkhead transcription factor binding sites and testosterone did not alter Forkhead box O 3A phosphorylation. The AR associated with sequences conferring repression in a manner that was stimulated by testosterone and was independent of DNA binding. In gel shift studies, octamer binding transcription factor (Oct)-1 bound two predicted Oct-1 sites within these sequences. Deletion of Oct-1 sites from reporter genes prevented repression by testosterone. Gene knockdown of Oct-1 blocked repression of MAFbx reporter gene activity by testosterone and binding of AR to sequences conferring repression. In conclusion, testosterone represses MAFbx expression via interactions of the AR with Oct-1 that are associated with sequences within the 5 ' untranslated region of the MAFbx promotor located just upstream of the first codon. This action of testosterone may contribute to beneficial actions of testosterone on muscle. (Endocrinology 149: 5449-5460, 2008) C1 [Zhao, Weidong; Pan, Jiangping; Wang, Xiaolei; Wu, Yong; Bauman, William A.; Cardozo, Christopher P.] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences, SCI, Bronx, NY 10468 USA. [Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences, SCI, Room 1E-02, Bronx, NY 10468 USA. EM chris.cardozo@mssm.edu FU Department of Veterans Affairs Rehabilitation Research and Development Service [B4162C, B3347K, B4616R] FX This work was supported by Grants B4162C, B3347K, and B4616R from the Department of Veterans Affairs Rehabilitation Research and Development Service. NR 44 TC 27 Z9 27 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2008 VL 149 IS 11 BP 5449 EP 5460 DI 10.1210/en.2008-0664 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 362JM UT WOS:000260194000016 PM 18599544 ER PT J AU Lawenda, BD Arnold, MG Tokarz, VA Silverstein, JR Busse, PM McIntyre, JE Deschler, DG Baldini, EH Kachnic, LA AF Lawenda, Brian D. Arnold, Michelle G. Tokarz, Valerie A. Silverstein, Joshua R. Busse, Paul M. McIntyre, James E. Deschler, Daniel G. Baldini, Elizabeth H. Kachnic, Lisa A. TI Analysis of radiation therapy for the control of Merkel cell carcinoma of the head and neck based on 36 cases and a literature review SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Review AB Merkel cell carcinoma (MCC) is a rare and aggressive epidermal cancer. We conducted a retrospective study and literature review to investigate the impact that radiation therapy has on local, regional, and distant control as part of the oncologic management of MCC of the head and neck and to further elucidate the role of radiation therapy with regard to regional control for the clinically uninvolved neck. We reviewed all registered cases of head and neck MCC that had occurred at four institutions from January 1988 through December 2005. Treatment and outcomes data were collected on patients with American Joint Committee on Cancer stage I, II, and III tumors. Local, regional, and distant control rates were calculated by comparing variables with the Fisher exact test; Kaplan-Meier analysis was used to report actuarial control data. Stage I to III head and neck MCC was identified in 36 patients-22 men and 14 women, aged 43 to 97 years (mean: 71.6) at diagnosis. Patients with stage I and II tumors were combined into one group, and their data were compared with those of patients with stage III tumors. Twenty-six patients (72%) had clinical stage I/II disease and 10 patients (28%) had clinical stage III disease. Median follow-up was 41 months for the stage IN group and 19 months for the stage III group. Based on examination at final follow-up visits, local recurrence was seen in 7 of the 36 patients (19%),for a local control rate of 81%. The 2-year actuarial local control rate for all stages of MCC was 83%; by treatment subgroup, the rates were 95% for those who had undergone radiation therapy to the primary site and 69% for those who had not-a statistically significant difference (p = 0.020). Based on information obtained at final follow-ups, 10 of the 36 patients (28%) experienced a regional recurrence, for a regional control rate of 72%. The 2-year actuarial regional control rate among all patients was 70%; by subgroup, rates were 82% for patients who had undergone regional node radiation therapy and 60% for those who had not-not a statistically significant difference (p = 0.225). Nine patients (25%) overall developed a distant metastasis, for a distant control rate of 75%. Salvage therapies included chemotherapy and/or radiation therapy to the metastatic site, but neither had any significant effect on survival. Regardless of treatment, the Kaplan-Meier survival curves leveled off at 30 months with 82% survival for the stage I/II group and at 19 months with 60% survival for the stage III group. We conclude that radiation therapy to the primary tumor site (either following resection or definitively) results in a local control rate of more than 90% in patients with head and neck MCC. We also found a trend toward improved regional control of the clinically negative neck with the addition of radiation therapy. C1 [Arnold, Michelle G.] USN, Med Ctr, Dept Otolaryngol, San Diego, CA 92134 USA. [Tokarz, Valerie A.] USN, Med Ctr, Dept Dermatol, San Diego, CA 92134 USA. [Lawenda, Brian D.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. [Lawenda, Brian D.] Indiana Univ, Sch Med, Dept Radiat Oncol, Indianapolis, IN 46202 USA. [Silverstein, Joshua R.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Busse, Paul M.; McIntyre, James E.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Baldini, Elizabeth H.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kachnic, Lisa A.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Lawenda, Brian D.] USN, San Diego Med Ctr, Dept Radiat Oncol, San Diego, CA 92134 USA. RP Lawenda, BD (reprint author), USN, San Diego Med Ctr, Dept Radiat Oncol, 34800 Bob Wilson Dr,Suite 14, San Diego, CA 92134 USA. EM brian.lawenda@med.navy.mil NR 30 TC 13 Z9 15 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD NOV PY 2008 VL 87 IS 11 BP 634 EP 643 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA V10PE UT WOS:000207475100009 PM 19006065 ER PT J AU Opler, MGA Buka, SL Groeger, J McKeague, I Wei, C Factor-Litvak, P Bresnahan, M Graziano, J Goldstein, JM Seidman, LJ Brown, AS Susser, ES AF Opler, Mark G. A. Buka, Stephen L. Groeger, Justina McKeague, Ian Wei, Catherine Factor-Litvak, Pam Bresnahan, Michaeline Graziano, Joseph Goldstein, Jill M. Seidman, Larry J. Brown, Alan S. Susser, Ezra S. TI Prenatal Exposure to Lead, delta-Aminolevulinic Acid, and Schizophrenia: Further Evidence SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE delta-aminolevulinic acid; developmental; lead; Pb; prenatal; prospective; psychosis; schizophrenia ID BLOOD LEAD; RISK; PREGNANCY; WORKERS; FAMINE; ALA; AIR AB BACKGROUND: A previously conducted study of prenatal lead exposure and schizophrenia using delta-aminolevulinic acid, a biologic marker of Ph exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959-1966) based in Oakland, California, suggested a possible association between prenatal Ph exposure and the development of schizophrenia in later life. OBJECTIVES: In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959-1966). Using similar methods, in this study we found results that suggest a comparable association in this cohort. METHODS: We pooled matched sets of cases and controls from both the California and New, England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education. RESULTS: The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 mu g/dL of blood Pb was 1.92 (95% confidence interval, 1.05-3.87; p = 0.03). CONCLUSION: Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders. C1 [Opler, Mark G. A.; Groeger, Justina; Wei, Catherine; Factor-Litvak, Pam; Bresnahan, Michaeline; Susser, Ezra S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Opler, Mark G. A.; Brown, Alan S.; Susser, Ezra S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Buka, Stephen L.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [McKeague, Ian] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Bresnahan, Michaeline; Brown, Alan S.; Susser, Ezra S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Graziano, Joseph] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Goldstein, Jill M.] Brigham & Womens Hosp, Dept Womens Hlth, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Opler, MGA (reprint author), Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA. EM mgo4@columbia.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU National Institutes of Health [5 T32 MH 13043]; National Alliance for Research on Schizophrenia and Depression Young Investigator Award; National Institute of Environmental Health Sciences Center [P30 ES 09089]; National Institute of Child Health and Human Development [NO1-HD-1-3334, NO1-1-HD-6-3258]; Public Health Institute, Berkeley, California FX Work for this article was supported in part by National Institutes of Health training grant 5 T32 MH 13043, National Alliance for Research on Schizophrenia and Depression Young Investigator Award, and National Institute of Environmental Health Sciences Center grant P30 ES 09089. The Child Health and Development Study has been supported by National Institute of Child Health and Human Development contracts NO1-HD-1-3334 arid NO1-1-HD-6-3258 and is administered by, the Public Health Institute, Berkeley, California (B. Cohn, principal investigator). NR 30 TC 45 Z9 47 U1 0 U2 5 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP 1586 EP 1590 DI 10.1289/ehp.10464 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500037 PM 19057716 ER PT J AU Chiu, Y Hart, JE Smith, TJ Hammond, SK Garshick, E Laden, F AF Chiu, Y. Hart, J. E. Smith, T. J. Hammond, S. K. Garshick, E. Laden, F. TI Nicotine Contamination in Particulate Matter Sampling SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Chiu, Y.; Hart, J. E.; Smith, T. J.; Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hart, J. E.; Garshick, E.; Laden, F.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hart, J. E.; Garshick, E.; Laden, F.] Harvard Univ, Sch Med, Boston, MA USA. [Hammond, S. K.] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci Div, Berkeley, CA 94720 USA. [Garshick, E.] VA Boston Healthcare Syst, Boston, MA USA. [Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S335 EP S335 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901398 ER PT J AU Chiu, Y Hart, JE Spiegelman, D Garshick, E Smith, TJ Laden, F AF Chiu, Y. Hart, J. E. Spiegelman, D. Garshick, E. Smith, T. J. Laden, F. TI Effectiveness of Smoking Policy in the US Trucking Industry Terminals SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Chiu, Y.; Hart, J. E.; Garshick, E.; Smith, T. J.; Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hart, J. E.; Garshick, E.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hart, J. E.; Garshick, E.] Harvard Univ, Sch Med, Boston, MA USA. [Spiegelman, D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Garshick, E.] VA Boston Healthcare Syst, Boston, MA USA. [Garshick, E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S317 EP S317 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901353 ER PT J AU Hart, JE Yanosky, JD Puett, RC Ryan, L Dockery, DW Smith, TJ Garshick, E Laden, F AF Hart, J. E. Yanosky, J. D. Puett, R. C. Ryan, L. Dockery, D. W. Smith, T. J. Garshick, E. Laden, F. TI Spatial Modeling of Air Pollution 1985-2000 in the Continental US SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Hart, J. E.; Yanosky, J. D.; Dockery, D. W.; Smith, T. J.; Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hart, J. E.; Ryan, L.; Garshick, E.; Laden, F.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hart, J. E.; Ryan, L.; Garshick, E.; Laden, F.] Harvard Univ, Sch Med, Boston, MA USA. [Puett, R. C.] Univ S Carolina, S Carolina Canc Prevent & Control Program, Columbia, SC 29208 USA. [Ryan, L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Garshick, E.] VA Boston Healthcare Syst, Boston, MA USA. [Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; Puett, Robin/A-4449-2012 OI Ryan, Louise/0000-0001-5957-2490; NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S332 EP S333 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901391 ER PT J AU Hart, JE Ryan, L Dockery, DW Smith, TJ Garshick, E Laden, F AF Hart, J. E. Ryan, L. Dockery, D. W. Smith, T. J. Garshick, E. Laden, F. TI Long-Term Ambient Multipollutant Exposures and Mortality SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Hart, J. E.; Dockery, D. W.; Smith, T. J.; Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hart, J. E.; Garshick, E.; Laden, F.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hart, J. E.; Garshick, E.; Laden, F.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, L.; Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Garshick, E.] VA Boston Healthcare, Boston, MA USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 0 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S333 EP S333 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901393 ER PT J AU Laden, F Hart, JE Componeschi, K Garshick, E AF Laden, F. Hart, J. E. Componeschi, K. Garshick, E. TI Predictors of Self-Reported Chronic Respiratory Symptoms in an Occupational Cohort SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Laden, F.; Hart, J. E.; Componeschi, K.; Garshick, E.] Harvard Univ, Sch Med, Boston, MA USA. [Laden, F.; Hart, J. E.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Laden, F.; Hart, J. E.; Componeschi, K.; Garshick, E.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Garshick, E.] VA Boston Healthcare Syst, Boston, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S329 EP S329 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901383 ER PT J AU Laden, F Chiu, Y Garshick, E Hart, JE AF Laden, F. Chiu, Y. Garshick, E. Hart, J. E. TI Effect Modification of Glutathione-S-transferases M1 Polymorphism on the Association Between Traffic Exposed Jobs and Inflammatory Response SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Laden, F.; Chiu, Y.; Hart, J. E.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Laden, F.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Laden, F.; Garshick, E.; Hart, J. E.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Laden, F.; Garshick, E.; Hart, J. E.] Harvard Univ, Sch Med, Boston, MA USA. [Garshick, E.] VA Boston Healthcare Syst, Boston, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S325 EP S326 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901375 ER PT J AU Park, S Wilker, EH Alexeeff, SE O'Neill, MS Litonjua, AA Poon, A Vokonas, PS Sparrow, D Sub, H Schwartz, J AF Park, S. Wilker, E. H. Alexeeff, S. E. O'Neill, M. S. Litonjua, A. A. Poon, A. Vokonas, P. S. Sparrow, D. Sub, H. Schwartz, J. TI Genes in the Pathways of Inflammatory Lung Diseases, Particulate Air Pollution and Heart Rate Variability SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Park, S.; O'Neill, M. S.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Wilker, E. H.; Alexeeff, S. E.; Sub, H.; Schwartz, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Litonjua, A. A.; Poon, A.] Harvard Univ, Sch Med, Boston, MA USA. [Vokonas, P. S.; Sparrow, D.] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S297 EP S298 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901300 ER PT J AU Wilker, E Ackerman-Alexceff, S Litonjua, A Wright, RO Sub, H Vokonas, P Sparrow, D Baccarelli, A Mittleman, M Schwartz, J AF Wilker, E. Ackerman-Alexceff, S. Litonjua, A. Wright, R. O. Sub, H. Vokonas, P. Sparrow, D. Baccarelli, A. Mittleman, M. Schwartz, J. TI Gene Environment Interactions and Postural Blood Pressure in Community Exposed Elderly Men: The VA Normative Aging Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Wilker, E.; Ackerman-Alexceff, S.; Wright, R. O.; Sub, H.; Baccarelli, A.; Mittleman, M.; Schwartz, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Litonjua, A.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Vokonas, P.; Sparrow, D.] VA Boston Healthcare Syst, Boston, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S129 EP S129 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900378 ER PT J AU Staley, BA Montenegro, MA Major, P Muzykewicz, DA Halpern, EF Kopp, CMC Newberry, P Thiele, EA AF Staley, Brigid A. Montenegro, Maria A. Major, Philippe Muzykewicz, David A. Halpern, Elkan F. Kopp, Claudine M. C. Newberry, Peter Thiele, Elizabeth A. TI Self-injurious behavior and tuberous sclerosis complex: Frequency and possible associations in a population of 257 patients SO EPILEPSY & BEHAVIOR LA English DT Article DE Tuberous sclerosis complex; Self-injurious behavior; Epilepsy; Frontal lobe; Tuber location; Behavioral problems ID FRONTAL-LOBE SEIZURES; ADULTS; AUTISM; GENE; IDENTIFICATION; DISABILITIES; AGGRESSION; EPILEPSY AB Self-injurious behavior (SIB) has been observed in people with tuberous sclerosis complex (TSC), although the frequency of SIB in TSC is largely unknown. SIB is associated with intellectual and developmental disabilities, but there is no single cause of SIB. We retrospectively examined the frequency of SIB in a population of 257 patients with TSC and determined possible associations with SIB. We found a 10% frequency of SIB in our TSC population. When compared with patients without psychiatric symptoms, we identified a significantly higher rate of electroencephalographic interictal spikes in the left frontal lobe and a significantly lower number of tubers in the left occipital, parietal, and posterior temporal lobes. We also found that frequency of TSC2 Mutation, history of infantile spasms, history of seizures, mental retardation, and autism are significantly associated with SIB. (C) 2008 Elsevier Inc. All rights reserved. C1 [Staley, Brigid A.; Montenegro, Maria A.; Major, Philippe; Muzykewicz, David A.; Kopp, Claudine M. C.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Newberry, Peter] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Carol & James Herscot Ctr Tuberous Sclerosis Comp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 32 TC 10 Z9 10 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2008 VL 13 IS 4 BP 650 EP 653 DI 10.1016/j.yebeh.2008.07.010 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 369NP UT WOS:000260701500013 PM 18703161 ER PT J AU Bertagnolli, MM Morgan, JA Fletcher, CDM Raut, CP Dileo, P Gill, RR Demetri, GD George, S AF Bertagnolli, Monica M. Morgan, Jeffrey A. Fletcher, Christopher D. M. Raut, Chandrajit P. Dileo, Palma Gill, Ritu R. Demetri, George D. George, Suzanne TI Multimodality treatment of mesenteric desmoid tumours SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Desmoid tumours; Familial adenomatous polyposis; Fibromatoses ID FAMILIAL ADENOMATOUS POLYPOSIS; CHEMOTHERAPY; ASSOCIATION; DACARBAZINE; DOXORUBICIN; MANAGEMENT; THERAPY AB Background: Desmoid tumours are rare neoplasms characterised by clonal proliferation of myofibroblasts that do not metastasise, but often exhibit an infiltrative pattern and functional impairment. When desmoids arise in the intestinal mesentery, surgical resection is seldom possible without life-altering loss of intestinal function. Methods: Retrospective review of the clinical management of 52 consecutive patients treated for desmoids of the intestinal mesentery from January 2001 to August 2006. A multidisciplinary treatment plan was developed based on primary disease extent, tumour behaviour and resectability. Patients with stable but unresectable disease were observed without treatment. Patients with resectable disease under-went surgery, and patients with unresectable progressing disease received chemotherapy, most commonly liposomal doxorubicin, followed by surgery if chemotherapy rendered the disease resectable. Results: At a median follow-up of 50.0 months (range 4.6-212), 50 patients (96%) have either no recurrence or radiographically stable disease. No patient requires total parenteral nutrition. Conclusion: These data indicate that the extent of disease; tumour behaviour and resectability are the important factors when defining a treatment plan for mesenteric desmoid tumours. A multidisciplinary approach of surgery combined with chemotherapy is an effective and function-sparing strategy for managing this disease. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Bertagnolli, Monica M.; Morgan, Jeffrey A.; Fletcher, Christopher D. M.; Raut, Chandrajit P.; Dileo, Palma; Gill, Ritu R.; Demetri, George D.; George, Suzanne] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Morgan, Jeffrey A.; Dileo, Palma; Demetri, George D.; George, Suzanne] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Bertagnolli, Monica M.; Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Fletcher, Christopher D. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gill, Ritu R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Demetri, George D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA. RP George, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM sgeorge2@partners.org FU Cancer Research FX Research funded in part by the Virginia and Daniel K. Ludwig Trust for Cancer Research. NR 19 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2008 VL 44 IS 16 BP 2404 EP 2410 DI 10.1016/j.ejca.2008.06.038 PG 7 WC Oncology SC Oncology GA 376ZM UT WOS:000261221500014 PM 18706807 ER PT J AU Pentimalli, F Palmieri, D Pacelli, R Garbi, C Cesari, R Martin, E Pierantoni, GM Chieffi, P Croce, CM Costanzo, V Fedele, M Fusco, A AF Pentimalli, Francesca Palmieri, Dario Pacelli, Roberto Garbi, Corrado Cesari, Rossano Martin, Eric Pierantoni, Giovanna Maria Chieffi, Paolo Croce, Carlo Maria Costanzo, Vincenzo Fedele, Monica Fusco, Alfredo TI HMGA1 protein is a novel target of the ATM kinase SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE HMGA1; ATM; DNA damage ID DOUBLE-STRAND BREAKS; DNA-DAMAGE; ATAXIA-TELANGIECTASIA; HISTONE H2AX; POSTTRANSLATIONAL MODIFICATIONS; CHROMATIN-STRUCTURE; IONIZING-RADIATION; TUMOR-SUPPRESSOR; HMGI(Y) PROTEIN; CANCER CELLS AB The high mobility group HMGA1 protein belongs to a family of architectural factors that play a role in chromosomal Organisation and gene transcription regulation. HMGA 1 overexpression represents a common feature of human malignant tumours and is causally associated with neoplastic transformation and metastatic progression. Recently, HMGA1 expression has been correlated with the presence of chromosomal rearrangements and suggested to promote genomic instability. Here, we report a novel interaction between HMGA1 protein and the ataxia-telangiectasia mutated (ATM) kinase, the major key player in the cellular response to DNA damage caused by several agents such as ionising radiation (IR). We identified an SQ motif on HMGA1, which is effectively phosphorylated by ATM in vitro and in vivo. Interestingly, confocal microscopy revealed that HMGA1 colocalises with the activated form of ATM (ATM S1981p). Moreover, HMGA1 ectopic expression decreases cell survival following exposure to IR as assessed by clonogenic survival in MCF-7 cells, further supporting the hypothesis that HMGA1 might act as a downstream target of the ATM pathway in response to DNA damage. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Pentimalli, Francesca; Palmieri, Dario; Garbi, Corrado; Pierantoni, Giovanna Maria; Costanzo, Vincenzo; Fedele, Monica; Fusco, Alfredo] Univ Naples Federico 2, Fac Med & Chirurg Napoli, CNR, Ist Endocrinol & Oncol Sperimentale,Dipartimento, I-80131 Naples, Italy. [Pentimalli, Francesca; Cesari, Rossano; Martin, Eric] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Pacelli, Roberto] Univ Naples Federico 2, CNR, Ist Biostruct & Bioimmagini, Dipartimento Diagnost Immagini & Radioterapia, I-80131 Naples, Italy. [Cesari, Rossano] HSR TIGET, I-20132 Milan, Italy. [Martin, Eric] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med & Genet, Boston, MA 02115 USA. [Chieffi, Paolo] Univ Naples Federico 2, Dipartimento Med Sperimentale, I-80138 Naples, Italy. [Croce, Carlo Maria] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA. [Costanzo, Vincenzo] Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. [Fusco, Alfredo] NOGEC Naples Oncogenom Ctr CEINGE, I-80131 Naples, Italy. RP Fusco, A (reprint author), Univ Naples Federico 2, Ist Endocrinol & Oncol Sperimentale Gaetano Salva, Via Pansini 5, I-80131 Naples, Italy. EM afusco@napoli.com RI Pentimalli, Francesca/K-4936-2014; Fedele, Monica/C-1417-2015; OI Pentimalli, Francesca/0000-0003-4740-6801; Pacelli, Roberto/0000-0002-2048-7675; chieffi, paolo/0000-0001-8483-5635; Fusco, Alfredo/0000-0003-3332-5197; Fedele, Monica/0000-0002-9171-1312 FU Associazione Italiana Ricerca sul Cancro (AIRC); Progetto Strategico Oncologia, Consiglio Nazionale delle Ricerche, the Ministero dell'Universit e Cella Ricerca Scientifica e Tecnologica (MIUR); NOGEC-Naples Oncogenomic Center; Associazione Partenopea per le Ricerche Oncologiche (APRO) FX We are very grateful to Dr. M.B. Kastan for providing the FLAGATM wild-type and kinase-dead constructs. We thank Dr. G. Viglietto and Dr. F. Carlomagno for technical hints and valuable suggestions. This work was supported by grants from the Associazione Italiana Ricerca sul Cancro (AIRC), Progetto Strategico Oncologia, Consiglio Nazionale delle Ricerche, the Ministero dell'Universit e Cella Ricerca Scientifica e Tecnologica (MIUR). This work was supported from NOGEC-Naples Oncogenomic Center. We thank the Associazione Partenopea per le Ricerche Oncologiche (APRO) for its support. NR 41 TC 12 Z9 14 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2008 VL 44 IS 17 BP 2668 EP 2679 DI 10.1016/j.ejca.2008.07.033 PG 12 WC Oncology SC Oncology GA 381UZ UT WOS:000261562700025 PM 18783938 ER PT J AU Villablanca, EJ Mora, JR AF Villablanca, Eduardo J. Mora, Jorge R. TI A two-step model for Langerhans cell migration to skin-draining LN SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Editorial Material DE CCR7; CXCR4; DC; Langerhans cells; Skin ID DERMAL DENDRITIC CELLS; STEADY-STATE CONDITIONS; LYMPH-NODES; IN-VIVO; CONTACT HYPERSENSITIVITY; VIRAL IMMUNITY; T-CELLS; MATURATION; TRAFFICKING; EXPRESSION AB Although the role of Langerhans cells (LC) in skin immune responses is still a matter of debate, it is known that LC require the chemokine receptor CCR7 for migrating to skin-draining LN. A report in the current issue of the European Journal of Immunology unfolds some of the intricacies of LC migration, showing that LC need CXCR4, but not CCR7, for their migration from the epidermis to the dermis. Thus, LC migration to skin-draining LN occurs in two distinct phases: a first step from the epidermis to the dermis regulated by CXCR4 and a second CCR7-dependent step from the dermis to LN. Here we discuss the potential implications of this new two-step LC migration paradigm. C1 [Villablanca, Eduardo J.; Mora, Jorge R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02115 USA. RP Mora, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02115 USA. EM j_rodrigo_mora@hms.harvard.edu RI Villablanca, Eduardo/E-1380-2016 OI Villablanca, Eduardo/0000-0001-9522-9729 FU NIDDK NIH HHS [P30 DK043351] NR 48 TC 38 Z9 38 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2008 VL 38 IS 11 BP 2975 EP 2980 DI 10.1002/eji.200838919 PG 6 WC Immunology SC Immunology GA 380HY UT WOS:000261458000002 PM 18991275 ER PT J AU Guenova, E Volz, T Sauer, K Kaesler, S Muller, MR Wolbing, F Chen, KM Schwarzler, C Brossart, P Rocken, M Biedermann, T AF Guenova, Emmanuella Volz, Thomas Sauer, Karin Kaesler, Susanne Mueller, Martin R. Woelbing, Florian Chen, KoMing Schwaerzler, Christoph Brossart, Peter Roecken, Martin Biedermann, Tilo TI IL-4-mediated fine tuning of IL-12p70 production by human DC SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Cytokines; DC; Human; Inflammation; Skin ID HUMAN DENDRITIC CELLS; HUMAN TH2 CELLS; CD4(+) T-CELLS; ATOPIC-DERMATITIS; IN-VIVO; INTERFERON-GAMMA; ADAPTIVE IMMUNITY; AUTOIMMUNE-DISEASE; INTERLEUKIN (IL)-4; CD8-T-CELL MEMORY AB IL-4 is expressed at high levels in allergic diseases and dominates the early phases of multiple acquired immune responses. However, the precise role of IL-4 during early inflammation and its impact on the differentiation of newly recruited DC precursors remains elusive. In order to characterize the impact of IL-4 on the differentiation of human DC, we investigated the role of IL-4 on the differentiation of monocytes into DC. Human DC were differentiated from peripheral blood precursors under either low or high concentrations of IL-4. We analyzed their cytokine profile and capacity to polarize T-cell differentiation. Concentrations of 5 (low) and 50 (high) ng/mL IL-4 induced two distinct types of DC. DC differentiated under low-dose IL-4 (5 ng/mL) produced almost no IL-12p70, and primed naive CD(4+) T cells allowing IL-4 secretion and Th2 induction. In contrast, DC generated under high concentrations of IL-4 (50ng/mL) produced large amounts of IL-12p70, low IL-10 and primed naive CD(4+) T cells to become Th1 cells. Thus, we demonstrate that the Th2 cell cytokine IL-4 decisively determines the phenotype of ongoing immune responses by orchestrating the functional phenotype of newly immigrating DC precursors. C1 [Guenova, Emmanuella; Volz, Thomas; Sauer, Karin; Kaesler, Susanne; Woelbing, Florian; Chen, KoMing; Roecken, Martin; Biedermann, Tilo] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Mueller, Martin R.] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. [Schwaerzler, Christoph] Novartis Inst Biomed Res, Vienna, Austria. [Brossart, Peter] Univ Bonn, Dept Haematol & Oncol, D-5300 Bonn, Germany. RP Biedermann, T (reprint author), Univ Tubingen, Dept Dermatol, Tubingen, Germany. EM tilo.biedermann@med.uni-tuebingen.de RI Guenova, Emmanuella/A-4656-2015 FU Deutsche Forschungsgemeinschaft [Bi 696/3-1, SFB 685]; Landesstiftung Baden-Wurttemberg [P-LS-AL/17]; University of Tubingen, Germany [17126810, 1261150] FX We thank G. Jung (Eberhard-Karls University of Tubingen, Germany) for mAb and K. Ghoreschi and A. Bringmann (Eberhard-Karls University of Tubingen) for scientific discussions. We thank C. Grimmel (Eberhard-Karls University of Tubingen) for excellent assistance operating the cell sorting. We also thank W. Hotzenecker (Eberhard-Karls University of Tubingen) for critically reading the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG Bi 696/3-1; SFB 685), Landesstiftung Baden-Wurttemberg, (P-LS-AL/17) and the Fortune Program of the University of Tubingen (17126810 and 1261150), Germany. NR 72 TC 28 Z9 29 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2008 VL 38 IS 11 BP 3138 EP 3149 DI 10.1002/eji.200838463 PG 12 WC Immunology SC Immunology GA 380HY UT WOS:000261458000017 PM 18924208 ER PT J AU Tegeder, I Adolph, J Schmidt, H Woolf, CJ Geisslinger, G Lotsch, J AF Tegeder, Irmgard Adolph, Jan Schmidt, Heimut Woolf, Clifford J. Geisslinger, Gerd Loetsch, Joern TI Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase 1 haplotype SO EUROPEAN JOURNAL OF PAIN LA English DT Article DE Genetics; Experimental pains; Tetrahydrobipterin; Human ID NITRIC-OXIDE SYNTHASE; NEUROPATHIC PAIN; GENE GCH1; N-TYPE; T-TYPE; TETRAHYDROBIOPTERIN; CHANNELS; PROTEIN; POLYMORPHISMS; BIOSYNTHESIS AB Background: Carriers of a particular haplotype of the GTP cyclohydrolase gene (GCH1) had less pain after surgery for chronic lumbar radiculopathy and a decreased sensitivity to some experimental mechanical pain stimuli. Ex-vivo, GCH1 upregulation and BH4 productio after forskolin stimulation were reduced, while baseline BH4 concentrations were not affected. This suggested that the haplotype may mainly exert its modulating function when the GCH1 system is provoked. The present study aimed at (i) testing this hypothesis and (ii) independently reproducing the pain-decreasing effects of a particular GCH1 haplotype having been previously associated with pain protection. Methods: Experimental pain models with sensitization (local skin inflammation, dermal capsaicin application) and without sensitizaiton (punctate pressure, blunt pressure, thermal and electrical pain) were assessed in 10 homozygous and 22 non-carriers of the particular GCH1 haplotype reportedly associated with pain protection. GCH1, iNOS upregulation and BH4 production were assessed ex-vivo in white blood cells after lipopolysaccharide stimulation for 24 h. Results: Carriers of the particular GCH1 haplotype addressed in this study had higher thresholds to punctate mechanical pain (von Frey hairs) following local skin inflammation (18.1 +/- 11.3 vs. 9 +/- 2.8 g; p = 0.005) and, to a lesser degree, to heat pain following capsaicin sensitization (35.2 +/- 0.9 vs. 36.6 +/- 2.4 degrees C; p = 0.026). In contrast, heat and pressure thresholds and tolerance to electrical stimulation in pain models without sensitization did not differ among the genotypes. GCH1, BH4 and iNOS upregulation in white blood cells after lipopolysaccharide stimulation were decreased in carriers of the GCH1 haplotype, which verified that the genotype groups differed with respect to regulation of the biopterin pathway. Conclusions: This study verifies previous results that decreased GCH1 function or inducibility as a result of genetic polymorphisms protects against pain. This study extents previous results by showing that this pain protection is mainly conferred under conditions of hyperalgesia resulting from sensitization, supporting specific functions of BH4 in relation to particular aspects of pain. (C) 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. C1 [Tegeder, Irmgard; Adolph, Jan; Schmidt, Heimut; Geisslinger, Gerd; Loetsch, Joern] Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, D-60590 Frankfurt, Germany. [Woolf, Clifford J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. [Woolf, Clifford J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lotsch, J (reprint author), Univ Frankfurt, Inst Clin Pharmacol, Pharmazentrum Frankfurt ZAFES, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM j.loetsch@em.uni-frankfurt.de OI Lotsch, Jorn/0000-0002-5818-6958; Tegeder, Irmgard/0000-0001-7524-8025 FU Dr. Robert Pfleger Foundation; Wilhelm Sander Foundation [2006.111.1]; NIH [NS058870] FX The study was supported by the Dr. Robert Pfleger Foundation and the Wilhelm Sander Foundation (2006.111.1, I.T. and J.L.), Germany and the NIH (NS058870 C.J.W.). We thank A. Haussler, I.N. Grundei and A. Kirchhof for excellent technical assistance. NR 28 TC 62 Z9 64 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD NOV PY 2008 VL 12 IS 8 BP 1069 EP 1077 DI 10.1016/j.ejpain.2008.02.004 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 362AA UT WOS:000260169400013 PM 18374612 ER PT J AU Tzermiadianos, MN Renner, SM Phillips, FM Hadjipavlou, AG Zindrick, MR Havey, RM Voronov, M Patwardhan, AG AF Tzermiadianos, Michael N. Renner, Susan M. Phillips, Frank M. Hadjipavlou, Alexander G. Zindrick, Michael R. Havey, Robert M. Voronov, Michael Patwardhan, Avinash G. TI Altered disc pressure profile after an osteoporotic vertebral fracture is a risk factor for adjacent vertebral body fracture SO EUROPEAN SPINE JOURNAL LA English DT Article DE Osteoporosis; Compression fractures; Adjacent fractures; Cement augmentation; Biomechanics; Intervertebral disc ID VIVO BIOMECHANICAL EVALUATION; COMPRESSIVE FOLLOWER PRELOAD; FLEXION-EXTENSION RESPONSE; PERCUTANEOUS VERTEBROPLASTY; LUMBAR SPINE; SUBSEQUENT FRACTURES; INTERVERTEBRAL DISC; FINITE-ELEMENT; SURFACE STRAIN; KYPHOPLASTY AB This study investigated the effect of endplate deformity after an osteoporotic vertebral fracture in increasing the risk for adjacent vertebral fractures. Eight human lower thoracic or thoracolumbar specimens, each consisting of five vertebrae were used. To selectively fracture one of the endplates of the middle VB of each specimen a void was created under the target endplate and the specimen was flexed and compressed until failure. The fractured vertebra was subjected to spinal extension under 150 N preload that restored the anterior wall height and vertebral kyphosis, while the fractured endplate remained significantly depressed. The VB was filled with cement to stabilize the fracture, after complete evacuation of its trabecular content to ensure similar cement distribution under both the endplates. Specimens were tested in flexion-extension under 400 N preload while pressure in the discs and strain at the anterior wall of the adjacent vertebrae were recorded. Disc pressure in the intact specimens increased during flexion by 26 +/- 14%. After cementation, disc pressure increased during flexion by 15 +/- 11% in the discs with un-fractured endplates, while decreased by 19 +/- 26.7% in the discs with the fractured endplates. During flexion, the compressive strain at the anterior wall of the vertebra next to the fractured endplate increased by 94 +/- 23% compared to intact status (p < 0.05), while it did not significantly change at the vertebra next to the unfractured endplate (18.2 +/- 7.1%, p > 0.05). Subsequent flexion with compression to failure resulted in adjacent fracture close to the fractured endplate in six specimens and in a non-adjacent fracture in one specimen, while one specimen had no adjacent fractures. Depression of the fractured endplate alters the pressure profile of the damaged disc resulting in increased compressive loading of the anterior wall of adjacent vertebra that predisposes it to wedge fracture. This data suggests that correction of endplate deformity may play a role in reducing the risk of adjacent fractures. C1 [Tzermiadianos, Michael N.; Havey, Robert M.; Patwardhan, Avinash G.] Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA. [Tzermiadianos, Michael N.; Hadjipavlou, Alexander G.] Univ Hosp Crete, Iraklion, Crete, Greece. [Renner, Susan M.; Havey, Robert M.; Voronov, Michael; Patwardhan, Avinash G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Phillips, Frank M.] Rush Univ, Chicago, IL 60612 USA. [Zindrick, Michael R.] Hinsdale Orthopaed Associates, Hinsdale, IL USA. RP Patwardhan, AG (reprint author), Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, 2160 S 1st Ave, Maywood, IL 60153 USA. EM apatwar@lumc.edu FU Department of Veterans Affairs, Washington, DC; Kyphon Inc., Sunnyvale, CA FX Institutional research support provided by the Department of Veterans Affairs, Washington, DC, and Kyphon Inc., Sunnyvale, CA. NR 52 TC 13 Z9 20 U1 0 U2 1 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 NOV PY 2008 VL 17 IS 11 BP 1522 EP 1530 DI 10.1007/s00586-008-0775-x PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 373DI UT WOS:000260950800017 PM 18795344 ER PT J AU Roodman, GD AF Roodman, G. David TI Novel targets for myeloma bone disease SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE bone disease; myeloma; novel treatments; osteoblast; osteoclast ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MALIGNANT PLASMA-CELLS; MULTIPLE-MYELOMA; IN-VIVO; OSTEOLYTIC LESIONS; RECEPTOR ACTIVATOR; OSTEOBLAST DIFFERENTIATION; OSTEOCLAST FORMATION; MARROW MICROENVIRONMENT; PROTEASOME INHIBITION AB Background: Multiple myeloma (MM) is a plasma cell malignancy in which osteolytic bone lesions develop in over 80% of patients. The increased bone destruction results from increased osteoclast formation and activity, which occurs adjacent to marrow sites involved with MM cells. This is accompanied by suppressed or absent osteoblast differentiation and activity, resulting in severely impaired bone formation and development of purely osteolytic lesions. Objective: The pathophysiology underlying this bone remodeling is reviewed, and potential new strategies to treat MM bone disease are discussed. Results: Recent advances in our understanding of factors involved in pathogenesis of MM bone disease have identified novel therapeutic targets. Several of these are or will be in clinical trials soon. Conclusion: Agents which target the tumor and bone-destructive process, such as the immunomodulatory drugs (IMiDs) or bortezomib, in combination with novel anti-resorptives should be effective. These combinations should be in clinical trials in the next few years. It is unclear if these treatments will be able to 'heal' bone lesions in MM patients. C1 Univ Pittsburgh, Sch Med, Dept Med Hematol Oncol, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Roodman, GD (reprint author), Univ Pittsburgh, Sch Med, Dept Med Hematol Oncol, Vet Affairs Pittsburgh Healthcare Syst, Univ Dr C,Res & Dev 151-U,Room 2E113, Pittsburgh, PA 15240 USA. EM Roodmangd@upmc.edu NR 85 TC 19 Z9 19 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD NOV PY 2008 VL 12 IS 11 BP 1377 EP 1387 DI 10.1517/14728220802447489 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 368JT UT WOS:000260618100006 PM 18851694 ER PT J AU Hall, DE Koenig, HG Meador, KG AF Hall, Daniel E. Koenig, Harold G. Meador, Keith G. TI HITTING THE TARGET: WHY EXISTING MEASURES OF "RELIGIOUSNESS" ARE REALLY REVERSE-SCORED MEASURES OF "SECULARISM" SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Article DE Religion; spirituality; measurement; precision; health ID HEALTH RESEARCH; SPIRITUALITY; MORTALITY; RELIGIOSITY; PROTESTANTS; ATTENDANCE; SERVICES; SUPPORT; JEWS AB Over 100 measures of religiousness and spirituality are used in research investigating the associations between religion and health. These measures are often used to assess "religiousness in general," but this approach lumps together widely divergent worldviews in ways that can distort religion beyond recognition. The authors suggest that the existing measures of religiousness are perhaps better understood as reverse-coded measures of "secularism." This argument suggests that the existing data regarding religiousness and health might be best interpreted as demonstrating a small, robust health liability associated with a deliberately secular worldview. If true, this conclusion might change the direction of future research, and it would imply that meaningful inferences about the health associations of religious practice will depend on developing tools that measure specific religions in their particularity. C1 [Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equities Res & Promot, Pittsburgh, PA USA. [Hall, Daniel E.] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. [Koenig, Harold G.; Meador, Keith G.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Meador, Keith G.] Duke Divin Sch, Dept Pastoral Theol, Durham, NC USA. RP Hall, DE (reprint author), Suite F 1206 Presbyterian,200 Lothrop St, Pittsburgh, PA 15213 USA. EM hallde@upmc.edu RI Koenig, Harold/F-7379-2011; Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 33 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD NOV-DEC PY 2008 VL 4 IS 6 BP 368 EP 373 DI 10.1016/j.explore.2008.08.002 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 373SD UT WOS:000260991900005 PM 18984548 ER PT J AU Garrett, LA Vargas, SO Drapkin, R Laufer, MR AF Garrett, Leslie A. Vargas, Sara O. Drapkin, Ronny Laufer, Marc R. TI Does the fimbria have an embryologic origin distinct from that of the rest of the fallopian tube? SO FERTILITY AND STERILITY LA English DT Editorial Material DE Fallopian tube; mullerian anomaly; fimbria; congenital fallopian tube atresia; embryology ID ATRESIA AB Objective: To propose a new theory describing the development of the fallopian tube fimbria. Design: Case series report. Setting: Metropolitan tertiary care children's hospital. Patient(s): Two girls, aged 12 and 20 years, who presented with pelvic pain. Intervention(s): Magnetic resonance imaging, laparoscopy with salpingectomy, and pathologic analysis. Main Outcome Measure(s): Description of a novel theory regarding the embryologic development of the fallopian tube and its fimbria. Result(s): In two non-sexually active girls the cause of their pelvic pain was found to be a hydrosalpinx associated with a discontinuous fallopian tube in which the fimbriated end did not directly communicate with the remainder of the fallopian tube. Conclusion(s): The two cases of pure congenital fallopian tube atresia, the presence of fimbriae in patients with mullerian (uterine, cervical, and vaginal) agenesis, and the role of the fimbria in ovarian-like and peritoneal cancers, support a novel hypothesis that the fimbria of the fallopian tube may arise separately from the rest of the tube. (Fertil Steril (R) 2008;90:2008.e5-e8. (C) 2008 by American Society for Reproductive Medicine.) C1 [Garrett, Leslie A.; Laufer, Marc R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gynecol,Dept Surg, Boston, MA 02115 USA. [Vargas, Sara O.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Laufer, MR (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gynecol,Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM marc.laufer@childrens.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 13 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2008 VL 90 IS 5 AR 2008.e5 DI 10.1016/j.fertnstert.2008.01.071 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA V13XQ UT WOS:000207699900028 PM 18353321 ER PT J AU Laine, L Curtis, SP Langman, M Jensen, DM Cryer, B Kaur, A Cannon, CP AF Laine, Loren Curtis, Sean P. Langman, Michael Jensen, Dennis M. Cryer, Byron Kaur, Amarjot Cannon, Christopher P. TI Lower Gastrointestinal Events in a Double-Blind Trial of the Cyclo-Oxygenase-2 Selective Inhibitor Etoricoxib and the Traditional Nonsteroidal Anti-Inflammatory Drug Diclofenac SO GASTROENTEROLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; VIDEO CAPSULE ENDOSCOPY; RHEUMATOID-ARTHRITIS; ASPIRIN USE; MULTINATIONAL ETORICOXIB; PLUS OMEPRAZOLE; OSTEOARTHRITIS; CELECOXIB; NAPROXEN; ULCER AB Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause lower gastrointestinal (GI) clinical events such as bleeding. Cyclo-oxygenase (COX)-2 selective inhibitors decrease upper GI events, but no prospective trial has prespecified assessment of lower GI clinical events. Methods: Patients 2:50 years old with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 or 90 mg qd) or diclofenac (150 mg qd). Lower GI clinical events, confirmed by a blinded adjudication committee, included perforation or obstruction requiring hospitalization or bleeding (gross or occult rectal bleeding without upper GI cause associated with hypotension, orthostatic changes in heart rate [>20 beats per minute] or blood pressure [ > 20 mmHg systolic or > 10 mmHg diastolic], hemoglobin drop >= 2 g/dl, or transfusion; or observed active bleeding or stigmata of hemorrhage). Results: We enrolled 34,701 patients with mean duration of therapy of 18 months. Rates were 0.32 and 0.38 lower GI clinical events per 100 patient-years for etoricoxib and diclofenac (hazard ratio [HR] = 0.84; 95% confidence interval [CI] , 0.63-1.13). Bleeding was the most common event (rates of 0.19 and 0.23 per 100 patient-years, respectively). Multivariable analysis revealed significant risk factors to be prior lower GI event (HR = 4.06; 95% CI, 2.93-5.62) and age >= 65 years (HR = 1.98; 95% CI, 1.45-2.71). Conclusions: A statistically significant decrease in lower GI clinical events was not seen with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. The risk of a lower GI clinical event with NSAID use seems to be constant over time, and the major risk factors are a prior lower GI event and older age. C1 [Laine, Loren] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Curtis, Sean P.; Kaur, Amarjot] Merck Res Labs, Rahway, NJ USA. [Langman, Michael] Univ Birmingham, Birmingham, W Midlands, England. [Jensen, Dennis M.] CURE DDRC, UCLA Geffen Sch Med, Los Angeles, CA USA. [Jensen, Dennis M.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Cryer, Byron] Univ Texas SW Med Sch, Dallas VA Med Ctr, Dept Med, Div Gastroenterol, Dallas, TX USA. [Cannon, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. RP Laine, L (reprint author), LA Cty USC Med Ctr, Room 12-137,1200 N State St, Los Angeles, CA 90033 USA. EM llaine@usc.edu NR 25 TC 55 Z9 58 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2008 VL 135 IS 5 BP 1517 EP 1525 DI 10.1053/j.gastro.2008.07.067 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 371YL UT WOS:000260868500020 PM 18823986 ER PT J AU Flores, MVC Hall, CJ Davidson, AJ Singh, PP Mahagaonkar, AA Zon, LI Crosier, KE Crosier, PS AF Flores, Maria Vega C. Hall, Chris J. Davidson, Alan J. Singh, Primal P. Mahagaonkar, Alhad A. Zon, Leonard I. Crosier, Kathryn E. Crosier, Philip S. TI Intestinal Differentiation in Zebrafish Requires Cdx1b, a Functional Equivalent of Mammalian Cdx2 SO GASTROENTEROLOGY LA English DT Article ID HOMEOBOX TRANSCRIPTION FACTOR; GUT DEVELOPMENT; MUTANT MICE; HOMEODOMAIN PROTEIN; PEPTIDE TRANSPORTER; ECTOPIC EXPRESSION; EPITHELIAL-CELLS; BINDING PROTEIN; TRANSGENIC MICE; HOX GENES AB Background & Aims: The ParaHox transcription factor Cdx2 is an essential determinant of intestinal phenotype in mammals throughout development, influencing gut function, homeostasis, and epithelial barrier integrity. Cdx2 expression demarcates the zones of intestinal stem cell proliferation in the adult gut, with deregulated expression implicated in intestinal metaplasia and cancer. However, in vivo analysis of these prospective roles has been limited because inactivation of Cdx2 in mice leads to preimplantation embryonic lethality. We used the zebrafish, a valuable model for studying gut development, to generate a system to further understanding of the role of Cdx2 in normal intestinal function and in disease states. Methods: We isolated and characterized the zebrafish cdx1b ortholog and analyzed its function by antisense morpholino gene knockdown. Results: We showed that zebrafish Cdx1b replaces the role of Cdx2 in gut development. Evolutionary studies have indicated that the zebrafish cdx2 loci were lost following the genome-wide duplication event that occurred in teleosts. Zebra-fish Cdx1b is expressed exclusively in the developing intestine during late embryogenesis and regulates intestinal cell proliferation and terminal differentiation. Conclusions: This work established an in vivo system to explore further the activity of Cdx2 in the gut and its impact on processes such as inflammation and cancer. C1 [Flores, Maria Vega C.; Hall, Chris J.; Singh, Primal P.; Mahagaonkar, Alhad A.; Crosier, Kathryn E.; Crosier, Philip S.] Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland 1, New Zealand. [Davidson, Alan J.] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Davidson, Alan J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp, Harvard Stem Cell Inst,Stem Cell Program, Boston, MA USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp, Harvard Stem Cell Inst,Div Hematol Oncol, Boston, MA USA. [Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Crosier, PS (reprint author), Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Private Bag 92019, Auckland 1, New Zealand. EM ps.crosier@auckland.ac.nz FU Foundation for Research, Science and Technology, New Zealand; NIH [DK077186-01A1, 2R01HL048801-15A2] FX The authors disclose the following: Supported by the Foundation for Research, Science and Technology, New Zealand (to P.S.C.); NIH grant DK077186-01A1 (to A.J.D.); and NIH grants 2R01HL048801-15A2 and HHMI (to L.I.Z). NR 56 TC 30 Z9 31 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 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2008 VL 135 IS 5 BP 1665 EP 1675 DI 10.1053/j.gastro.2008.07.024 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 371YL UT WOS:000260868500036 PM 18804112 ER PT J AU Matthews, AM AF Matthews, Annette M. TI Editorial on "Guideline-concordant hepatitis C virus testing and notification among patients with and without mental disorders" SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material C1 [Matthews, Annette M.] Portland VA Med Ctr, Portland, OR 97207 USA. [Matthews, Annette M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Matthews, AM (reprint author), Portland VA Med Ctr, POB 1035, Portland, OR 97207 USA. EM annette.matthews@med.va.gov NR 3 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 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2008 VL 30 IS 6 BP 493 EP 494 DI 10.1016/j.genhosppsych.2008.06.011 PG 2 WC Psychiatry SC Psychiatry GA 374EI UT WOS:000261025300001 PM 19061673 ER PT J AU Kilbourne, AM McCarthy, JF Himelhoch, S Welsh, D Hauser, P Blow, FC AF Kilbourne, Amy M. McCarthy, John F. Himelhoch, Seth Welsh, Deborah Hauser, Peter Blow, Frederic C. TI Guideline-concordant hepatitis C virus testing and notification among patients with and without mental disorders SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Mental disorders; Hepatitis C; Guideline-concordant care ID INFECTION; VETERANS; USERS AB Objective: We compared screening for hepatitis C virus (HCV), positive HCV test rates and test result notification among Veterans Affairs (VA) patients diagnosed with psychosis (e.g., schizophrenia, bipolar disorder) or depression or those with no Psychiatric diagnosis. Method: We identified all patients in the VA's External Peer Review Program national random sample of chart reviews regarding HCV care in fiscal year 2004. We then identified individuals diagnosed with psychosis or depression using data from the VA's National Psychosis and Depression registries. Using multivariable logistic regression and generalized estimating equation analyses, we evaluated associations between mental disorder diagnosis and receipt of HCV screening and notification of results. Results: Out of 19,397 patients, 94% received HCV tests. Of those tested, 6.9% were HCV positive, and of those who were positive, 48.2% were notified of their result within 60 days. After adjusting for demographic and clinical factors (including illicit drug use and comorbidities), individuals with psychosis or depression were no less likely to have a positive test or be notified of their result :! 60 days compared to nonpsychiatric groups. Those with drug use disorder diagnoses (OR=4.64; P <.001) and Blacks (OR=1.96; P <.001) were more likely to have a positive test. Conclusions: Study limitations included inability to fully control for sociodemographic Confounders (e.g., homelessness, incarceration), Nevertheless, we found that although the vast majority of patients were tested, only half were notified of test results. VA HCV prevention and follow-up strategies focus on enhanced notification overall and tailoring HCV risk reduction programs to minorities and those with drug use disorders. Published by Elsevier Inc. C1 [Kilbourne, Amy M.; McCarthy, John F.; Blow, Frederic C.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48105 USA. [Kilbourne, Amy M.; McCarthy, John F.; Welsh, Deborah; Blow, Frederic C.] VA Serious Mental Illness Treatment Res & Evaluat, Ann Arbor, MI 48105 USA. [Himelhoch, Seth] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Hauser, Peter] Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR 97239 USA. RP Kilbourne, AM (reprint author), Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [02-283, 07-115]; National Institute oil Drug Abuse [K23DA019820]; EPRP [05-024] FX This research was Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (02-283, 07-115, Dr. Kilbourne) and the National Institute oil Drug Abuse (K23DA019820; Dr. Himelhoch). 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 acknowledge the VA Office Of Quality and Performance for providing access to EPRP data (DUA #05-024). NR 12 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2008 VL 30 IS 6 BP 495 EP 500 DI 10.1016/j.genhosppsych.2008.06.002 PG 6 WC Psychiatry SC Psychiatry GA 374EI UT WOS:000261025300002 PM 19061674 ER PT J AU Richardson, LK Egede, LE Mueller, M Echols, CL Gebregziabher, M AF Richardson, Lisa K. Egede, Leonard E. Mueller, Martina Echols, Carrae L. Gebregziabher, Mulugeta TI Longitudinal effects of depression on glycemic control in veterans with Type 2 diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Longitudinal effects; Depression; Glycemic control; Veterans; Type 2 diabetes ID BLOOD-GLUCOSE CONTROL; COMORBID DEPRESSION; HEART-DISEASE; COMPLICATIONS; MELLITUS; ADULTS; CARE; METAANALYSIS; INDIVIDUALS; ASSOCIATION AB Objectives: To examine the longitudinal effects of depression on glycermic control in veterans with Type 2 diabetes. Methods: Data on 11.25 veterans with Type 2 diabetes were analyzed. A person-period dataset for each subject to cover 3-month intervals (36 time intervals) from April 1997 to March 2006 was created. Subjects were classified as depressed based on ICD-9 codes for depression. General linear mixed model regression was used to examine changes over time in HbA(1c) levels and whether the changes from baseline were different in depressed and nondepressed diabetic veterans, sequentially adjusting for baseline age, demographic variables and comorbidities (coronary heart disease. stroke and hypertension). Pooled t-tests were used to compare unadjusted mean HbA(1c) at each time point across the depressed and nondepressed groups. SAS was used for statistical analysis. Results: Ninety-seven percent were men. 48% were white, 27% were blacks and 25% were other. Mean age was 66 years and mean follow-up period was 4.1 years. Six percent (696/11,525) of the sample had diagnosed depression. Unadjusted mean HbA(1c), values were significantly J higher in depressed vs. nondepressed subjects at all time points. The adjusted mean HbA(1c) values over time in the final mixed model were significantly higher in depressed vs. nondepressed subjects (mean difference of 0.13; 95% CI [0.03; 0.22]; P=.008). In all adjusted models, differences in mean HbA(1c) Values were significantly higher in depressed vs. nondepressed Subjects with Type 2 diabetes. Conclusion: This study of veterans with Type 2 diabetes demonstrates that there is a significant longitudinal relationship between depression and glycemic control as measured by HbA(1c) and that depression is associated with persistently higher HbA(1c) levels over time. (c) 2008 Elsevier Inc. All rights reserved. C1 [Mueller, Martina] Med Univ S Carolina, Ctr Hlth Dispar Res, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Richardson, Lisa K.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Richardson, Lisa K.] Murdoch Univ, Sch Psychol, Murdoch, WA 6150, Australia. [Richardson, Lisa K.; Egede, Leonard E.; Mueller, Martina; Echols, Carrae L.; Gebregziabher, Mulugeta] Ralph H Johnson VAMC, Charleston VA TREP, Charleston, SC 29401 USA. [Mueller, Martina; Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU NIDDK NIH HHS [R01 DK081121, R01 DK081121-01A1, R01 DK081121-02, R01 DK081121-03] NR 21 TC 67 Z9 69 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2008 VL 30 IS 6 BP 509 EP 514 DI 10.1016/j.genhosppsych.2008.07.001 PG 6 WC Psychiatry SC Psychiatry GA 374EI UT WOS:000261025300004 PM 19061676 ER PT J AU Lefterova, MI Zhang, Y Steger, DJ Schupp, M Schug, J Cristancho, A Feng, D Zhuo, D Stoeckert, CJ Liu, XS Lazar, MA AF Lefterova, Martina I. Zhang, Yong Steger, David J. Schupp, Michael Schug, Jonathan Cristancho, Ana Feng, Dan Zhuo, David Stoeckert, Christian J., Jr. Liu, X. Shirley Lazar, Mitchell A. TI PPAR gamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale SO GENES & DEVELOPMENT LA English DT Article DE PPAR gamma; C/EBP; adipocyte; genome wide; ChIP-chip ID PROLIFERATOR-ACTIVATED RECEPTOR; RETINOID-X-RECEPTOR; MODEL-BASED ANALYSIS; GENE-EXPRESSION; TARGET GENES; TRANSCRIPTIONAL ACTIVITY; 3T3-L1 PREADIPOCYTES; ECTOPIC EXPRESSION; ANDROGEN RECEPTOR; RESPONSE ELEMENT AB Peroxisome proliferator-activated receptor gamma(PPAR gamma), a nuclear receptor and the target of anti-diabetic thiazolinedione drugs, is known as the master regulator of adipocyte biology. Although it regulates hundreds of adipocyte genes, PPAR gamma binding to endogenous genes has rarely been demonstrated. Here, utilizing chromatin immunoprecipitation (ChIP) coupled with whole genome tiling arrays, we identified 5299 genomic regions of PPAR gamma binding in mouse 3T3-L1 adipocytes. The consensus PPAR gamma/RXR gamma "DR-1"-binding motif was found at most of the sites, and ChIP for RXR alpha showed colocalization at nearly all locations tested. Bioinformatics analysis also revealed CCAAT/enhancer-binding protein (C/EBP)-binding motifs in the vicinity of most PPAR gamma-binding sites, and genome-wide analysis of C/EBP alpha binding demonstrated that it localized to 3350 of the locations bound by PPAR gamma. Importantly, most genes induced in adipogenesis were bound by both PPAR gamma and C/EBP alpha, while very few were PPAR gamma-specific. C/EBP beta also plays a role at many of these genes, such that both C/EBP alpha and beta are required along with PPAR gamma for robust adipocyte-specific gene expression. Thus, PPAR gamma and C/EBP factors cooperatively orchestrate adipocyte biology by adjacent binding on an unanticipated scale. C1 [Lefterova, Martina I.; Steger, David J.; Schupp, Michael; Cristancho, Ana; Feng, Dan; Zhuo, David; Lazar, Mitchell A.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Lefterova, Martina I.; Steger, David J.; Schupp, Michael; Cristancho, Ana; Feng, Dan; Zhuo, David; Lazar, Mitchell A.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Zhang, Yong; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Schug, Jonathan; Stoeckert, Christian J., Jr.] Univ Penn, Ctr Bioinformat, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. RP Lazar, MA (reprint author), Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. EM lazar@mail.med.upenn.edu RI Zhang, Yong/B-4838-2011; Feng, Dan/F-7205-2013 OI Zhang, Yong/0000-0001-6316-2734; FU NIH [R01 DK4970, R01 HG004069-02] FX We thank members of the Lazar laboratory for insightful discussions and reagents, Elisabetta Manduchi (University of Pennsylvania) for help with computational analysis, and Mathieu Lupien and Myles Brown (Dana-Farber Cancer Institute) for helpful discussion. This work was supported by NIH R01 DK4970 (to M. A. L.) and NIH R01 HG004069-02 (to X. S. L.). NR 61 TC 333 Z9 346 U1 4 U2 23 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 NOV 1 PY 2008 VL 22 IS 21 BP 2941 EP 2952 DI 10.1101/gad.1709008 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 368DY UT WOS:000260602700006 PM 18981473 ER PT J AU Nguyen, VT Love, AR Kunik, ME AF Nguyen, Vi T. Love, Almer Ray Kunik, Mark E. TI Preventing aggression in persons with dementia SO GERIATRICS LA English DT Article DE aggression; dementia; geriatric assessment; pain; depression; caregiver; psychotherapy ID RATING DEPRESSION SCALE; ALZHEIMERS-DISEASE; SELF; PREVALENCE; DISORDERS AB Persons with dementia often present with non-cognitive clinical symptoms, such as aggression, which can be distressing and dangerous to both caregiver and patient. Depression, pain, caregiver burden, and the quality of the caregiver-patient relationship can contribute to the onset of aggression. Given the risks involved with medication, there is a strong need for preventive and nonpharmacological interventions before such behaviors occur. This article gives practical recommendations for primary care physicians on how to prevent aggression in dementia patients by screening for and treating predictive factors. Clinically useful assessment instruments and treatment options are discussed, in addition to referral sources. C1 [Nguyen, Vi T.] Texas A&M Univ, Coll Med, Texas A&M Hlth Sci Ctr, College Stn, TX 77843 USA. [Love, Almer Ray] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Love, Almer Ray] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kunik, Mark E.] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Nguyen, VT (reprint author), Texas A&M Univ, Coll Med, Texas A&M Hlth Sci Ctr, College Stn, TX 77843 USA. NR 26 TC 10 Z9 10 U1 0 U2 3 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD NOV PY 2008 VL 63 IS 11 BP 21 EP 26 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 373QE UT WOS:000260986200006 PM 18998764 ER PT J AU Longas, MO Ruiz, A Yu, LY Hales, CA Garg, HG AF Longas, Maria O. Ruiz, Aliciavidal Yu, Lunyin Hales, Carles A. Garg, Hari G. TI Effect of Reduced Oxyheparin on the Gorwth of Bovine Pulmonary Artery Smooth Muscle Cells SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Longas, Maria O.; Ruiz, Aliciavidal] Purdue Univ Calumet, Hammond, IN USA. [Yu, Lunyin; Hales, Carles A.; Garg, Hari G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 66 BP 956 EP 956 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400075 ER PT J AU Saleemuddin, A Folkins, AK Garrett, L Garber, J Muto, MG Crum, CP Tworoger, S AF Saleemuddin, Aasia Folkins, Ann K. Garrett, Leslie Garber, Judy Muto, Michael G. Crum, Christopher P. Tworoger, Shelley TI Risk factors for a serous cancer precursor ("p53 signature") in women with inherited BRCA mutations SO GYNECOLOGIC ONCOLOGY LA English DT Article DE BRCA; p53; Fallopian tube neoplasms; Serous carcinoma; Ovarian neoplasms; Fimbria ID EPITHELIAL OVARIAN-CANCER; PROPHYLACTIC OOPHORECTOMY SPECIMENS; FALLOPIAN-TUBE CARCINOMA; ORAL-CONTRACEPTIVE USE; OVULATORY CYCLES; BREAST-CANCER; MUTANT P53; CARRIERS; DAMAGE; ASSOCIATION AB Objectives. Pelvic (ovarian) serous carcinomas frequently contain p53 Mutations. Recently, a candidate serous cancer precursor (the p53 signature with p53 mutations and other features in common with serous cancer has been discovered in distal fallopian tube mucosa. This study examined the relationship of putative ovarian cancer risk factors with the presence of p53 signatures in women with BRCA mutations (BRCA+). Methods. Fallopian tubes from 75 BRCA+ women were immunostained for p53 signatures and correlated with age at first childbirth, parity, oral contraceptive use, body mass index (BMI), and BRCA subtype (1 or 2). Statistical analysis was performed with the T-test or Chi-square analysis and logistic regression adjusting for age and parity. Results. Thirty-eight percent of the tubes contained p53 signatures, which were significantly associated with older age at first childbirth (mean 30.8 vs. 28.4 years; p = 0.04) and lower parity (mean 1.4 vs. 2.2: p=0.01) in univariate analyses. The unadjusted odds ratios were 3.8 (p-trend=0.04) for first childbirth >= 30 years versus <30 and 0.2 (p-trend=0.01) for parity >= 3 versus nulliparous women. After adjusting for age and parity, the trend for age at first childbirth became non-significant (adjusted odds ratio 3.5: p-trend=0.15). while that for parity remained significant (adjusted odds ratio 0.2; p-trend 0.02). Conclusions. The p53 signature is significantly associated with lower parity and possibly higher age at first childbirth. further linking this entity to serous cancer via risk factors associated with ovulation. The p53 signature merits consideration as a surrogate marker for serous cancer risk. (C) 2008 Elsevier Inc. All rights reserved. C1 [Saleemuddin, Aasia; Folkins, Ann K.; Crum, Christopher P.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Garrett, Leslie; Muto, Michael G.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Garber, Judy] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Tworoger, Shelley] Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Tworoger, Shelley] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tworoger, Shelley] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org OI Tworoger, Shelley/0000-0002-6986-7046 FU NCI [P50 CA 105009, KO8 CA 108748, 1R21CA124688-01A1]; Columbia Hospital For Women Research Foundation; Francis Ward Paine; Division of Women's and Perinatal Pathology; Brigham arid Women's Hospital FX This work was Supported by grants from the NCI (P50 CA 105009 [SPORE]: D. Cramer, PI), NCI KO8 CA 108748 (R Drapkin, PI, NCI 1R21CA124688-01A1 (CP Crum, PI), The Charlotte Geyer Foundation (CP Crum, PI), The Columbia Hospital For Women Research Foundation (CP Crum, PI), and the Francis Ward Paine and TSA Pemberton Funds from the Division of Women's and Perinatal Pathology, Brigham arid Women's Hospital. NR 39 TC 36 Z9 37 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2008 VL 111 IS 2 BP 226 EP 232 DI 10.1016/j.ygyno.2008.07.018 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 373QS UT WOS:000260987700012 PM 18718648 ER PT J AU Growdon, WB Boisvert, SL Akhavanfard, S Oliva, E Dias-Santagata, DC Kojiro, S Horowitz, NS Iafrate, AJ Borger, DR Rueda, BR AF Growdon, Whitfield B. Boisvert, Susan L. Akhavanfard, Sara Oliva, Esther Dias-Santagata, Dora C. Kojiro, Sakiko Horowitz, Neil S. Iafrate, A. John Borger, Darrell R. Rueda, Bo R. TI Decreased survival in EGFR gene amplified vulvar carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Epidermal growth factor receptor; Amplification; Vulvar cancer; Squamous cell carcinoma ID GROWTH-FACTOR-RECEPTOR; SQUAMOUS-CELL CARCINOMA; TYROSINE KINASE INHIBITORS; COLORECTAL-CANCER PATIENTS; HUMAN-PAPILLOMAVIRUS DNA; COPY NUMBER; PROTEIN EXPRESSION; LUNG-CANCER; INTRAEPITHELIAL NEOPLASIA; PCR AB Objective. We undertook an extensive molecular characterization of the epidermal growth factor receptor (EGFR) gene in vulvar squamous cell carcinomas to investigate EGFR mutation and/or genomic amplification and its association with EGFR protein expression, high-risk human papillomavirus (HPV) status and clinical outcome. Methods. A cohort of 51 vulvar cancer patients distributed across all FIGO stages was selected for immunohistochemistry (IHC) and fluorescence in situ hybridization. EGFR expression and gene amplification were correlated with high-risk HPV status, EGFR mutational status and clinical prognostic variables. Fisher's exact tests, Kaplan-Meier Survival estimates and a Cox proportional-hazards model were utilized. Results. EGFR gene amplification and chromosome 7 high polysomy were observed in 12% and 6% of cases, respectively. IHC of malignant tissue with 3+ staining demonstrated 100% sensitivity and 79% specificity to detect EGFR gene amplification, yielding a 39% positive predictive value. Decreased survival (p<0.025) was observed in patients with gene amplification, and was associated with a more statistically robust 3.3 hazard ratio(p<0.005) in the Cox proportional-hazards model that controlled for age at diagnosis, stage and lymph node metastasis. Univariate analysis confirmed that EGFR gene amplification was associated with the absence of high-risk HPV (p<0.001). Common activating EGFR gene mutations were not identified. Conclusion. A subset of patients with vulvar squamous cell carcinoma was identified with EGFR gene amplification that was HPV-independent and associated with poor prognosis. Given the association of EGFR amplification with response to targeted therapy in other turner types, these patients may be candidates for therapeutic strategies that target the EGFR pathway. (C) 2008 Elsevier Inc. All rights reserved. C1 [Growdon, Whitfield B.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reproduct Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Boisvert, Susan L.; Borger, Darrell R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Akhavanfard, Sara; Oliva, Esther; Dias-Santagata, Dora C.; Kojiro, Sakiko; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Horowitz, Neil S.] Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reproduct Biol, Vincent Obstet & Gynecol Serv, THR 901A,55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org FU Vincent Memorial Research; Advanced Medical Research Foundation; MGH Cancer Center funds FX We thank Shyamala Maheswaran for mutational analysis assistance and Hideo Sakamoto and Anne Friel for PCR guidance. We also thank Leif Ellisen for critical reading of the manuscript. This work was supported by Vincent Memorial Research, Advanced Medical Research Foundation and MGH Cancer Center funds. NR 49 TC 22 Z9 22 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2008 VL 111 IS 2 BP 289 EP 297 DI 10.1016/j.ygyno.2008.07.038 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 373QS UT WOS:000260987700023 PM 18768215 ER PT J AU Pearson, SD Knudsen, AB Scherer, RW Weissberg, J Gazelle, GS AF Pearson, Steven D. Knudsen, Amy B. Scherer, Roberta W. Weissberg, Jed Gazelle, G. Scott TI Assessing The Comparative Effectiveness Of A Diagnostic Technology: CT Colonography SO HEALTH AFFAIRS LA English DT Article ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; EFFECTIVENESS INFORMATION; COLORECTAL NEOPLASIA; IMAGING TECHNOLOGIES; VIRTUAL COLONOSCOPY; SYSTEMATIC REVIEWS; CANCER AB Medical imaging is a prime example of an innovation that has brought important advances to medical care while triggering concerns about potential overuse and excessive costs. Many hopes are riding on comparative effectiveness research to help guide better decision making to improve quality and value. But the dynamic nature of medical imaging poses challenges for the traditional paradigms of evidentiary review and analysis at the heart of comparative effectiveness. This paper discusses these challenges and presents policy lessons for manufacturers, evidence reviewers, and decisionmakers, illustrated by an assessment of a prominent emerging imaging technique: computed tomography (CT) colonography. [Health Affairs 27, no. 6 (2008): 1503-1514; 10.1377/hlthaff.27.6.1503] C1 [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Technol Assessment, Inst Clin & Econ Review, Boston, MA 02114 USA. [Scherer, Roberta W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Weissberg, Jed] Permanente Federat, Qual & Performance Improvement, Oakland, CA USA. [Gazelle, G. Scott] Mass Gen, Dept Radiol, Boston, MA USA. RP Pearson, SD (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Inst Clin & Econ Review, Boston, MA 02114 USA. EM spearson@icer-review.org NR 23 TC 17 Z9 17 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2008 VL 27 IS 6 BP 1503 EP 1514 DI 10.1377/hlthaff.27.6.1503 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 370NQ UT WOS:000260769300006 PM 18997205 ER PT J AU Rodriguez, KL Appelt, CJ Switzer, GE Sonel, AF Arnold, RM AF Rodriguez, Keri L. Appelt, Cathleen J. Switzer, Galen E. Sonel, Ali F. Arnold, Robert M. TI Veterans' decision-making preferences and perceived involvement in care, for chronic heart failure SO HEART & LUNG LA English DT Article ID PATIENT COMMUNICATION; MEDICAL ENCOUNTER; ELDERLY-PATIENTS; PATIENTS DESIRE; CANCER-PATIENTS; CHRONIC ILLNESS; INFORMATION; OUTCOMES; PARTICIPATION; SATISFACTION AB BACKGROUND: Patients with heart failure require a great deal of information about their disease, but it is also important to know about their preferences for involvement in medical decision making and about factors that may influence their preferences so that patients' needs, values, and preferences can be met by clinicians. OBJECTIVES: We assessed patients' preferred role and perceived level of involvement in medical decision making and tested the effects of patients' age and role preference on perceived involvement in medical decision making. METHODS: We conducted a telephone survey of 90 adults being treated for heart failure by a Veterans Affairs primary care provider or cardiologist. Patients' preferred role in treatment decisions was assessed using the Control Preferences Scale. Perceptions about their involvement in decision making during the most recent clinic visit was measured using a subscale of the Perceived Involvement in Care Scale. Descriptive, correlational, and generalized linear regression analyses were conducted. RESULTS: Most patients were elderly (mean = 70.1 years), male (94.4%), and white (85.6%), and had New York Heart Association class 11 disease (55.6%). Forty-three patients (47.8%) preferred a passive role in decision making, 19 patients (21.1%) preferred an active role, and 28 patients (31.1%) preferred a collaborative role. Most patients believed that their decision-making involvement was relatively passive, as indicated by a mean score of .96 (range, 0-4) on the Perceived Involvement in Care Scale decision-making subscale. Older age was associated with passive role preference (r =.263; P <.05) and less perceived involvement in decision making (r = -.279; P <.01). In addition, less perceived involvement in decision making during the last clinic visit was associated with a preference for a more passive decision-making role (r = p.355; P <.01). Generalized linear regression analysis indicated that when patients' perceived decision-making involvement was regressed on age and patients' role preferences, age was no longer significantly associated with involvement (beta = -.196; P =.061), but that control preferences Continued to exhibit an independent effect on perceived involvement in medical decision making (beta -.341; P =.003). CONCLUSION: The results Suggest that the preferences of patients with heart failure for a more passive role in decision making may be a stronger independent predictor of patients' perceived involvement in decision making than patients' age. (Heart Lung (R) 2008,37:440-448.) C1 [Rodriguez, Keri L.; Switzer, Galen E.; Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Rodriguez, Keri L.; Switzer, Galen E.; Arnold, Robert M.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Rodriguez, Keri L.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Appelt, Cathleen J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Edcu & Clin Ctr, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Div Cardiol, Pittsburgh, PA USA. [Sonel, Ali F.] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15260 USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care & Med Eth, Pittsburgh, PA 15260 USA. [Arnold, Robert M.] Univ Pittsburgh, Inst Enhance Palliat Care, Pittsburgh, PA USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Bldg 2,Room 4083E 151C-H, Pittsburgh, PA 15206 USA. NR 55 TC 14 Z9 14 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD NOV-DEC PY 2008 VL 37 IS 6 BP 440 EP 448 DI 10.1016/j.hrtlng.2008.02.003 PG 9 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 372QP UT WOS:000260916700005 PM 18992627 ER PT J AU Mansour, M Forleo, GB Pappalardo, A Heist, EK Avella, A Laurenzi, F De Girolamo, P Bencardino, G Dello Russo, A Mantica, M Ruskin, JN Tondo, C AF Mansour, Moussa Forleo, Giovanni B. Pappalardo, Augusto Heist, E. Kevin Avella, Andrea Laurenzi, Francesco De Girolamo, Piergiuseppe Bencardino, Gianluigi Dello Russo, Antonio Mantica, Massimo Ruskin, Jeremy N. Tondo, Claudio TI Initial experience with the Mesh catheter for pulmonary vein isolation in patients with paroxysmal atrial fibrillation SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Balloon catheter; Catheter ablation; Mesh ablator; Pulmonary vein isolation ID BALLOON CATHETER; ABLATION SYSTEM; ANATOMY; SAFETY AB BACKGROUND A novel catheter design (HD Mesh ablator, Bard) combining high-density circumferential mapping and direct radio-frequency (RF) energy delivery has been developed to map and isolate the pulmonary veins (PVs). OBJECTIVE The purpose of this study was to assess the feasibility of the Mesh catheter for PV isolation in patients with paroxysmal atrial fibrillation (AF). METHODS Twenty consecutive patients (mean age 56.4 +/- 12.2 years; 16 men) with paroxysmal drug-refractory AF were referred for ablation. The procedure was performed in a stepwise manner: PV isolation was initially attempted with the Mesh ablator, and if that was not successful, a conventional ablation approach was then used. RESULTS A total of 73 PVs including seven veins with left common ostium were targeted. Successful deployment of the Mesh was achieved in all but four veins (94.5%). Using the Mesh catheter for ablation, PV isolation was achieved in 46 (63%) of the 73 PVs. The mean (RF) ablation time required to achieve complete isolation was 12.4 +/- 6.1 minutes per PV. The Mesh-only approach allowed isolation of all veins in eight (40 to) patients. In combination with conventional ablation, successful PV isolation was achieved in 71 (97%) of 73 PVs. No complications attributable to the Mesh ablator occurred in this series. CONCLUSIONS PV isolation using the Mesh catheter is feasible and may simplify the current PV isolation procedures. With the current catheter design, PV isolation could be achieved in 63 to of PVs. A Larger Mesh diameter with an over-the-wire design may help improve the acute success rate. C1 [Tondo, Claudio] Univ Cattolica Sacro Cuore, St Camillo Forlanini Hosp, Cardiac Arrhythmia & Heart Failure Res Inst, Div Cardiol, I-00151 Rome, Italy. [Mansour, Moussa; Heist, E. Kevin; Ruskin, Jeremy N.; Tondo, Claudio] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. RP Tondo, C (reprint author), Univ Cattolica Sacro Cuore, St Camillo Forlanini Hosp, Cardiac Arrhythmia & Heart Failure Res Inst, Div Cardiol, Piazza Carlo Forlanini 1, I-00151 Rome, Italy. EM c.tondo@libero.it RI Forleo, Giovanni/G-8788-2012 NR 20 TC 24 Z9 24 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 NOV PY 2008 VL 5 IS 11 BP 1510 EP 1516 DI 10.1016/j.hrthm.2008.08.024 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 370GY UT WOS:000260751900003 PM 18984524 ER PT J AU Singh, SM Heist, EK Donaldson, DM Collins, RM Chevalier, J Mela, T Ruskin, JN Mansour, MC AF Singh, Sheldon M. Heist, E. Kevin Donaldson, David M. Collins, Ryan M. Chevalier, Jianping Mela, Theofanie Ruskin, Jeremy N. Mansour, Moussa C. TI Image integration using intracardiac ultrasound to guide catheter ablation of atrial fibrillation SO HEART RHYTHM LA English DT Article DE Image integration; Atrial fibrillation; Intracardiac echocardiogram; Ablation; Ultrasound ID INITIAL-EXPERIENCE; ECHOCARDIOGRAPHY; VALIDATION; HEART AB BACKGROUND Three-dimensional (3D) reconstruction of the left atrium (LA) can be performed using real-time intracardiac echocardiography (ICE) to facilitate image integration during atrial fibrillation (AF) ablation. Current users of this technology generally image the LA indirectly from the right atrium (RA). OBJECTIVE The purpose of this study was to assess the feasibility and accuracy of image integration with placement of the ICE catheter directly in the LA to visualize the LA. METHODS Thirty consecutive patients undergoing an AF ablation with the CARTO-Sound system were enrolled. A 10-Fr phased-array ICE catheter was used to obtain two-dimensional echocardiographic images of the LA; in 15 patients the ICE probe was placed in the LA, and in 15 patients it was placed only in the RA. Sequential images were obtained and merged with a preacquired computed tomography/magnetic resonance image. The accuracy of image integration was assessed by the value of the average image integration error after surface registration. RESULTS Thirty patients (60% paroxysmal AF, LA size = 42 +/- 7 mm, ejection fraction = 62% +/- 10%) were studied. There was no difference in the time required to create the LA anatomic map and perform image integration with imaging from the LA versus the RA (22 +/- 22 vs. 24 +/- 16 minutes; P = .8). The number of ultrasound contours obtained was also similar (LA = 26 +/- 17 vs. RA = 24 +/- 16; P = .7). The average integration error was less with direct LA imaging (LA = 1.83 +/- 0.32 vs. RA = 2.52 +/- 0.58 mm; P = .0004). CONCLUSION Direct LA imaging with ICE is feasible and results in improved LA visualization and image integration. C1 [Singh, Sheldon M.; Heist, E. Kevin; Donaldson, David M.; Collins, Ryan M.; Chevalier, Jianping; Mela, Theofanie; Ruskin, Jeremy N.; Mansour, Moussa C.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, MC (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM mmansour@partners.org FU Royal College of Physicians and Surgeons of Canada FX This study was supported by a Detweiler Travelling Fellowship from the Royal College of Physicians and Surgeons of Canada (to S.M.S.). NR 12 TC 27 Z9 27 U1 0 U2 3 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 NOV PY 2008 VL 5 IS 11 BP 1548 EP 1555 DI 10.1016/j.hrthm.2008.08.027 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 370GY UT WOS:000260751900010 PM 18984531 ER PT J AU Morishima, C Morgan, TR Everhart, JE Wright, EC Apodaca, MC Gretch, DR Shiffman, ML Everson, GT Lindsay, KL Lee, WM Lok, ASF Dienstag, JL Ghany, MG Curto, TM AF Morishima, Chihiro Morgan, Timothy R. Everhart, James E. Wright, Elizabeth C. Apodaca, Minjun C. Gretch, David R. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Lee, William M. Lok, Anna S. F. Dienstag, Jules L. Ghany, Marc G. Curto, Teresa M. CA HALT C Trial Grp TI Interpretation of Positive Transcription-Mediated Amplification Test Results from Polymerase Chain Reaction-Negative Samples Obtained After Treatment of Chronic Hepatitis C SO HEPATOLOGY LA English DT Article ID INTERFERON-ALPHA THERAPY; RNA QUALITATIVE ASSAY; HCV RNA; VIRUS-RNA; VIROLOGICAL RESPONSE; PEGINTERFERON ALPHA-2A; FOLLOW-UP; RIBAVIRIN; TRIAL; TMA AB The siemens VERSANT (R) transcription-mediated amplification (TMA) assay is extremely sensitive for the detection of hepatitis C virus (HCV) RNA in serum. Eleven of 180 subjects in the Hepatitis C Antiviral Long-term Treatment against cirrhosis (HALT-C) Trial who achieved polymerase chain reaction (PCR)-defined sustained virological response (SVR) at week 72 also had TMA-positive results from the same blood draw; six were positive on repeat testing. We report the follow-up on these 11 patients, and the reproducibility of TMA test results from PCR-negative samples in relationship to antiviral treatment outcome. Peginterferon and ribavirin treatment was initiated in 1145 prior interferon nonresponders with advanced hepatic fibrosis. Treatment was continued for 48 weeks if patients had undetectable HCV RNA by PCR at treatment week 20. Frozen serum samples from weeks 12, 20, 24,48, and 72 were subsequently tested by TMA. Nine of the I I patients returned for testing (median, 30 months after the week 72 visit), and all had undetectable HCV RNA by TMA and PCR. Among 759 PCR-negative samples obtained during treatment that were tested twice by TMA, 17% overall exhibited consistently positive results, and 21% exhibited inconsistently positive results. SVR was more likely if TMA was consistently negative than if consistently or inconsistently positive. With continued treatment, patients with inconsistently positive TMA results were more likely to become TMA-negative than TMA-positive (P < 0.0001). Conclusion; In PCR-negative samples, positive TMA results may indicate the presence of low levels of HCV RNA. However, because patients with positive TMA results may achieve SVR, management decisions during therapy should not be based on a single positive TMA test result. (HEPATOLOGY 2008;48:1412-1419.) C1 [Morishima, Chihiro; Apodaca, Minjun C.; Gretch, David R.] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Wright, Elizabeth C.] NIDDKD, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Shiffman, Mitchell L.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO 80202 USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Lok, Anna S. F.] Univ Michigan, Div Gastroenterol, Med Ctr, Ann Arbor, MI 48109 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA USA. [Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. RP Morishima, C (reprint author), Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. RI Lok, Anna /B-8292-2009; Lopes Lera, Daniele/H-6081-2016; Acorsi, Rayanne/H-6066-2016; Vieira Teixeira, Jorge Juarez/H-6495-2016; MOREIRA NETO, LUIZ JORGE/H-6588-2016; OLIVEIRA, WELLINGTON/H-6591-2016; Borges Padilha Ferreira, Fabiana/H-6597-2016; Beletini, Lucimara Fatima/H-6083-2016; Cristina Ferreira, Erika /H-6607-2016; OI MOREIRA NETO, LUIZ JORGE/0000-0002-7407-4120; Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases [N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328]; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health [M01RR-06192, M01RR-01066, M01RR-00051, M01RR-00827, M01RR-00633, M01RR-00043, M01RR-00042, M01RR-00065]; Hoffmann-La Roche, Inc; Bayer Diagnostics FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases under contract numbers N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327 and N01-DK-9-2328, with supplemental funds from the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers M01RR-06192, M01RR-01066, M01RR-00051, M01RR-00827, M01RR-00633, M01RR-00043, M01RR-00042, and M01RR-00065). Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc. through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. Financial support was also provided by Bayer Diagnostics through a Clinical Trial Agreement with the National Institutes of Health and a Research and Technology Development Agreement with the University of Washington. NR 19 TC 18 Z9 19 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 NOV PY 2008 VL 48 IS 5 BP 1412 EP 1419 DI 10.1002/hep.22487 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368BP UT WOS:000260596600010 PM 18816437 ER PT J AU McGovern, BH Dayyeh, BAK Chung, RT AF McGovern, Barbara H. Dayyeh, Barham K. Abu Chung, Raymond T. TI Avoiding Therapeutic Pitfalls: The Rational Use of Specifically Targeted Agents Against Hepatitis C Infection SO HEPATOLOGY LA English DT Review ID VIRUS SERINE-PROTEASE; NONNUCLEOSIDE POLYMERASE INHIBITOR; MUTATIONS CONFERRING RESISTANCE; ALPHA-2A (40 KD)/RIBAVIRIN; TREATMENT-NAIVE PATIENTS; HCV GENOTYPE-1 PATIENTS; REPLICATION IN-VITRO; ANTIVIRAL ACTIVITY; PEGINTERFERON ALPHA-2A; ANTIRETROVIRAL THERAPY AB The development of specifically targeted antiviral agents against hepatitis C is a major therapeutic advance that promises to markedly improve treatment response rates in patients with chronic infection. However, rapid emergence of drug resistance has already been described, the consequences of which are not yet understood. Although there are important differences between hepatitis C (HCV) and human immunodeficiency virus (HIV) infection, the judicious use of candidate agents against HCV should be guided by principles that have been established in the HIV therapeutic arena. In this review, we attempt to draw useful parallels between the development of antiretroviral therapy for HIV and preliminary data on antiviral agents for hepatitis C virus infection. Applying concepts learned in HIV therapeutics will hopefully lead to a prudent and cautious path in HCV treatment paradigms, particularly with respect to drug resistance. (HEPATOLOGY 2008;48:1700-1712.) C1 [McGovern, Barbara H.] Lemuel Shattuck Hosp, Div Infect Dis, Jamaica Plain, MA USA. [McGovern, Barbara H.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Dayyeh, Barham K. Abu] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Dayyeh, Barham K. Abu] Harvard Univ, Sch Med, Boston, MA USA. RP McGovern, BH (reprint author), Tufts Univ, Sch Med, Lemuel Shattuck Hosp, Medford, MA 02155 USA. EM bmcgovern@tufts-nemc.org; rtchung@partners.org NR 112 TC 17 Z9 18 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 NOV PY 2008 VL 48 IS 5 BP 1700 EP 1712 DI 10.1002/hep.22563 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368BP UT WOS:000260596600039 PM 18972443 ER PT J AU Nosho, K Kawasaki, T Chan, AT Ohnishi, M Suemoto, Y Kirkner, GJ Fuchs, CS Ogino, S AF Nosho, K. Kawasaki, T. Chan, A. T. Ohnishi, M. Suemoto, Y. Kirkner, G. J. Fuchs, C. S. Ogino, S. TI Cyclin D1 is frequently overexpressed in microsatellite unstable colorectal cancer, independent of CpG island methylator phenotype SO HISTOPATHOLOGY LA English DT Article DE CCND1; CDKN1A; CIMP; colon cancer; CpG island methylator phenotype; cyclin; DNA methylation; microsatellite instability; p21 ID POPULATION-BASED SAMPLE; REAL-TIME PCR; AGE-OF-ONSET; BETA-CATENIN; MOLECULAR ALTERATIONS; E-CADHERIN; EXPRESSION; INSTABILITY; PATHWAY; CIMP AB Aims: Cyclin D1 and cyclin-dependent kinases are commonly activated in colorectal cancer. Microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) are important molecular classifiers in colorectal cancer. The aim was to clarify the relationship between cyclin D1, MSI and CIMP. Methods and results: Among 865 colorectal cancers with MSI and CIMP data, 246 tumours (28.4%) showed cyclin D1 overexpression by immunohistochemistry. DNA methylation in p14 and eight CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) was quantified by real-time polymerase chain reaction (MethyLight). Both MSI-high and CIMP-high were associated with cyclin D1 overexpression (P < 0.0001). After tumours were stratified by MSI and CIMP status, the relationship between MSI-high and cyclin D1 persisted (P <= 0.02), whereas the relationship between CIMP-high and cyclin D1 did not. Cyclin D1 overexpression was correlated with BRAF mutation (P = 0.0001), p27 loss (P = 0.0007) and p16 loss (P = 0.02), and inversely with p53 expression (P = 0.0002) and p21 loss (P < 0.0001). After stratification by MSI status, the inverse relationship between cyclin D1 and p21 loss still persisted (P < 0.008). Conclusions: Cyclin D1 activation is associated with MSI and inversely with p21 loss in colorectal cancers. Cyclin D1 may play an important role in the development of MSI-high tumours, independent of CIMP status. C1 [Ogino, S.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Nosho, K.; Kawasaki, T.; Ohnishi, M.; Suemoto, Y.; Fuchs, C. S.; Ogino, S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, A. T.; Kirkner, G. J.; Fuchs, C. S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Chan, A. T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ogino, S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU US National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation (EIF) National Colorectal Cancer Research Alliance (NCCRA); Japanese Society for Promotion of Science FX This work was supported by The US National Institute of Health (NIH) grants P01 CA87969, P01 CA55075, P50 CA127003 and K07 CA122826 (to S.O.), and in part by grants from the Bennett Family Fund and the Entertainment Industry Foundation (EIF) National Colorectal Cancer Research Alliance (NCCRA). K.N. was supported by a fellowship grant from the Japanese Society for Promotion of Science. These funding sponsors had no role or involvement in the study design, the collection, analysis or interpretation of data, or writing and submission of the manuscript. We deeply thank the Nurses' Health Study and Health Professionals Followup Study cohort participants, who have generously agreed to provide us with biological specimens and information through responses to questionnaires. We thank Walter Willett, Sue Hankinson and many other staff members who implemented and have maintained the cohort studies. NR 49 TC 27 Z9 30 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD NOV PY 2008 VL 53 IS 5 BP 588 EP 598 DI 10.1111/j.1365-2559.2008.03161.x PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 364PC UT WOS:000260346600010 PM 18983468 ER PT J AU Bassett, IV Giddy, J Wang, B Lu, Z Losina, E Freedberg, KA Walensky, R AF Bassett, I. V. Giddy, J. Wang, B. Lu, Z. Losina, E. Freedberg, K. A. Walensky, R. P. TI Routine, voluntary HIV testing in Durban, South Africa: correlates of HIV infection SO HIV MEDICINE LA English DT Article DE correlates of HIV infection; HIV testing; routine HIV testing; South Africa ID HEALTH LITERACY; ACCEPTANCE; ATTITUDES; BEHAVIOR; BOTSWANA; UGANDA; AIDS AB Background Routine HIV testing is increasingly recommended in resource-limited settings. Our objective was to evaluate factors associated with a new diagnosis of HIV infection in a routine HIV testing programme in South Africa. Methods We established a routine HIV testing programme in an out-patient department in Durban, South Africa. All registered adults were offered a rapid HIV test; we surveyed a sample of tested patients. Results During the 12-week study, 1414 adults accepted HIV testing. Of those, 463 (32.7%) were HIV-infected. Seven hundred and twenty (50.9%) were surveyed. Compared with married women, unmarried men were at the highest risk of HIV [odds ratio (OR) 6.84; 95% confidence interval (CI) 3.45-23.55], followed by unmarried women (OR 5.90; 95% CI 3.25-10.70) and married men (OR 4.00; 95% CI 2.04-7.83). Age 30-39 years (compared with >= 50 years; OR 5.10; 95% CI 2.86-9.09), no prior HIV test (OR 1.45; 95% CI 1.07-2.27) and an imperfect HIV knowledge score (OR 2.32; 95% CI 1.24-4.35) were also associated with HIV infection. Conclusion In a routine HIV testing programme in South Africa, rates of previously undiagnosed HIV were highest among men, young and unmarried patients, and those with poorer HIV knowledge. Better interventions are needed to improve HIV knowledge and decrease HIV risk behaviour. C1 [Bassett, I. V.; Walensky, R. P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bassett, I. V.; Wang, B.; Lu, Z.; Losina, E.; Freedberg, K. A.; Walensky, R. P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Giddy, J.] McCord Hosp, Durban, South Africa. [Losina, E.; Freedberg, K. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, E.; Freedberg, K. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Walensky, R. P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, E.] Brigham & Womens Hosp, Div Orthoped Surg, Boston, MA 02115 USA. [Freedberg, K. A.; Walensky, R. P.] Harvard Ctr AIDS Res CFAR, Boston, MA USA. RP Bassett, IV (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ibassett@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [T32 AI07433, T32 AI007433, R01 AI058736, K24 AI062476, K23 AI 068458, K23 AI068458, K23 AI068458-03, P30 AI060354] NR 22 TC 12 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD NOV PY 2008 VL 9 IS 10 BP 863 EP 867 DI 10.1111/j.1468-1293.2008.00635.x PG 5 WC Infectious Diseases SC Infectious Diseases GA 366QS UT WOS:000260499100004 PM 18754802 ER PT J AU Robertson, NG Jones, SM Sivakumaran, TA Giersch, ABS Jurado, SA Call, LM Miller, CE Maison, SF Liberman, MC Morton, CC AF Robertson, Nahid G. Jones, Sherri M. Sivakumaran, Theru A. Giersch, Anne B. S. Jurado, Sara A. Call, Linda M. Miller, Constance E. Maison, Stephane F. Liberman, M. Charles Morton, Cynthia C. TI A targeted Coch missense mutation: a knock-in mouse model for DFNA9 late-onset hearing loss and vestibular dysfunction SO HUMAN MOLECULAR GENETICS LA English DT Article ID PRODUCT OTOACOUSTIC EMISSIONS; MENIERES-DISEASE; VWFA2 DOMAIN; LCCL DOMAIN; DEAFNESS; GENE; MICE; IDENTIFICATION; POTENTIALS; FAMILIES AB Mutations in COCH (coagulation factor C homology) are etiologic for the late- onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. We introduced the G88E mutation by gene targeting into the mouse and have created a Coch(G88E/G88E) mouse model for the study of DFNA9 pathogenesis and cochlin function. Vestibular- evoked potential (VsEP) thresholds of Coch(G88E/G88E) mice were elevated at all ages tested compared with wild- type littermates. At the oldest ages, two out of eight Coch(G88E/G88E) mice had no measurable VsEP. Auditory brainstem response (ABR) thresholds of Coch(G88E/G88E) mice were substantially elevated at 21 months but not at younger ages tested. At 21 months, four of eight Coch(G88E/G88E) mice had absent ABRs at all frequencies tested and two of three Coch(G88E/+) mice had absent ABRs at three of four frequencies tested. Distortion product otoacoustic emission amplitudes of Coch(G88E/G88E) mice were substantially lower than Coch(+/+) mice and absent in the same Coch(G88E/G88E) mice with absent ABRs. These results suggest that vestibular function is affected beginning as early as 11 months when cochlear function appears to be normal, and dysfunction increases with age. Hearing loss declines substantially at 21 months of age and progresses to profound hearing loss at some to all frequencies tested. This is the only mouse model developed to date where hearing loss begins at such an advanced age, providing an opportunity to study both progressive age- related hearing loss and possible interventional therapies. C1 [Robertson, Nahid G.; Sivakumaran, Theru A.; Jurado, Sara A.; Call, Linda M.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Sivakumaran, Theru A.; Giersch, Anne B. S.; Call, Linda M.; Maison, Stephane F.; Liberman, M. Charles; Morton, Cynthia C.] Harvard Univ, Sch Med, Boston, MA USA. [Giersch, Anne B. S.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Miller, Constance E.; Maison, Stephane F.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otol & Laryngol, Boston, MA 02114 USA. [Jones, Sherri M.] E Carolina Univ, Dept Commun Sci & Disorders, Greenville, NC USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol, 77 Ave Louis Pasteur,NRB 160, Boston, MA 02115 USA. EM cmorton@partners.org FU NIDCD NIH HHS [P30 DC005209, R01 DC006443-03, DC0118, DC03402, DC006443, R01 DC006443, R01 DC003402]; PHS HHS [P30-05209] NR 30 TC 23 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2008 VL 17 IS 21 BP 3426 EP 3434 DI 10.1093/hmg/ddn236 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 359GI UT WOS:000259974000015 PM 18697796 ER PT J AU Chavarro, JE Toth, TL Sadio, SM Hauser, R AF Chavarro, Jorge E. Toth, Thomas L. Sadio, Sonita M. Hauser, Russ TI Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic SO HUMAN REPRODUCTION LA English DT Article DE soy; isoflavones; semen analysis; sperm concentration; infertility ID ESTROGEN-RECEPTOR-ALPHA; ENVIRONMENTAL ESTROGENS; TESTOSTERONE LEVELS; NEONATAL EXPOSURE; MALE RATS; FREQUENCY QUESTIONNAIRE; MARMOSET MONKEYS; UNITED-STATES; FORMULA MILK; PHYTOESTROGENS AB BACKGROUND: High isoflavone intake has been related to decreased fertility in animal studies, but data in humans are scarce. Thus, we examined the association of soy foods and isoflavones intake with semen quality parameters. METHODS: The intake of 15 soy-based foods in the previous 3 months was assessed for 99 male partners of subfertile couples who presented for semen analyses to the Massachusetts General Hospital Fertility Center. Linear and quantile regression were used to determine the association of soy foods and isoflavones intake with semen quality parameters while adjusting for personal characteristics. RESULTS: There was an inverse association between soy food intake and sperm concentration that remained significant after accounting for age, abstinence time, body mass index, caffeine and alcohol intake and smoking. In the multivariate-adjusted analyses, men in the highest category of soy food intake had 41 million sperm/ml less than men who did not consume soy foods (95% confidence interval = -74, -8; P, trend = 0.02). Results for individual soy isoflavones were similar to the results for soy foods and were strongest for glycitein, but did not reach statistical significance. The inverse relation between soy food intake and sperm concentration was more pronounced in the high end of the distribution (90th and 75th percentile) and among overweight or obese men. Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume. CONCLUSIONS: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. C1 [Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Chavarro, Jorge E.; Toth, Thomas L.; Sadio, Sonita M.; Hauser, Russ] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Toth, Thomas L.; Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Sadio, Sonita M.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chavarro, JE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM jchavarr@hsph.harvard.edu FU National Institute of Environmental Health Sciences (NIEHS) [ES09718, ES00002]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [T32 DK07703]; Yerby Postdoctoral Fellowship FX Supported by National Institute of Environmental Health Sciences (NIEHS) grants ES09718 and ES00002, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) training grant T32 DK07703 and the Yerby Postdoctoral Fellowship Program. NR 48 TC 64 Z9 66 U1 6 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 2008 VL 23 IS 11 BP 2584 EP 2590 DI 10.1093/humrep/den243 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 361QT UT WOS:000260142900024 PM 18650557 ER PT J AU Gong, WS Haburcakova, C Merfeld, DM AF Gong, Wangsong Haburcakova, Csilla Merfeld, Daniel M. TI Vestibulo-Ocular Responses Evoked Via Bilateral Electrical Stimulation of the Lateral Semicircular Canals SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Neural prosthesis; vestibular; vestibulo-ocular response (VOR) ID VESTIBULAR PROSTHESIS; SQUIRREL-MONKEY; VOR AB We investigated the vestibulo-ocular responses (VORs) evoked by bilateral electrical stimulation of the nerves innervating horizontal semicircular canals in squirrel monkeys and compared these responses to those evoked by unilateral stimulation. In response to sinusoidal modulation of the electrical pulse rate, the VOR for bilateral stimulation roughly equals the addition of the responses evoked by unilateral right ear and unilateral left ear stimulation; the VOR time constants were about the same for bilateral and unilateral stimulation and both were much shorter than for normal animals. In response to individual pulse stimulation, the VOR evoked by bilateral stimulation closely matches the point-by-point addition of responses evoked by unilateral right ear and unilateral left ear stimulation. We conclude that, to first order, the VOR responses evoked by bilateral stimulation are the summation of the responses evoked by unilateral stimulation. These findings suggest that-from a physiologic viewpoint-unilateral and bilateral vestibular prostheses are about equally viable. Given these findings, one possible advantage of a bilateral prosthesis is higher gain. However, at least for short-term stimulation such as that studied herein, no inherent advantage in terms of the response time constant ("velocity storage") was found. C1 [Gong, Wangsong; Haburcakova, Csilla; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Gong, Wangsong; Haburcakova, Csilla; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Gong, WS (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. EM wangsong_gong@meei.harvard.edu; csilla_haburcakova@meei.harvard.edu; dan_merfeld@meei.harvard.edu FU National Institutes of Health through National Institute of Deafness and Other Communication Disorders (NIDCD) [R01 DC-03066, R01 DC-008167] FX This work was supported by the National Institutes of Health through National Institute of Deafness and Other Communication Disorders (NIDCD) Grants R01 DC-03066 and R01 DC-008167. NR 17 TC 27 Z9 27 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD NOV PY 2008 VL 55 IS 11 BP 2608 EP 2619 DI 10.1109/TBME.2008.2001294 PG 12 WC Engineering, Biomedical SC Engineering GA 371XI UT WOS:000260865600014 PM 18990631 ER PT J AU Leslie, DS Dascher, CC Cembrola, K Townes, MA Hava, DL Hugendubler, LC Mueller, E Fox, L Roura-Mir, C Moody, DB Vincent, MS Gumperz, JE Illarionov, PA Besra, GS Reynolds, CG Brenner, MB AF Leslie, David S. Dascher, Christopher C. Cembrola, Katherine Townes, Maria A. Hava, David L. Hugendubler, Lynne C. Mueller, Elisabetta Fox, Lisa Roura-Mir, Carme Moody, D. Branch Vincent, Michael S. Gumperz, Jenny E. Illarionov, Petr A. Besra, Gurdyal S. Reynolds, Carol G. Brenner, Michael B. TI Serum lipids regulate dendritic cell CD1 expression and function SO IMMUNOLOGY LA English DT Article DE cell surface molecules; dendritic cells; human; lipid mediators; T cells ID PROLIFERATOR-ACTIVATED RECEPTORS; PPAR-GAMMA; ANTIGEN PRESENTATION; T-CELLS; MOLECULAR-MECHANISMS; LYMPHOCYTES-T; RECOGNITION; MATURATION; RESTRICTS; PATHWAYS AB Dendritic cells (DCs) are highly potent antigen-presenting cells (APCs) and play a vital role in stimulating naive T cells. Treatment of human blood monocytes with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 stimulates them to develop into immature dendritic cells (iDCs) in vitro. DCs generated by this pathway have a high capacity to prime and activate resting T cells and prominently express CD1 antigen-presenting molecules on the cell surface. The presence of human serum during the differentiation of iDCs from monocytes inhibits the expression of CD1a, CD1b and CD1c, but not CD1d. Correspondingly, T cells that are restricted by CD1c showed poor responses to DCs that were generated in the presence of human serum, while the responses of CD1d-restricted T cells were enhanced. We chemically fractionated human serum to isolate the bioactive factors that modulate surface expression of CD1 proteins during monocyte to DC differentiation. The human serum components that affected CD1 expression partitioned with polar organic soluble fractions. Lysophosphatidic acid and cardiolipin were identified as lipids present in normal human serum that potently modulate CD1 expression. Control of CD1 expression was mediated at the level of gene transcription and correlated with activation of the peroxisome proliferator-activated receptor (PPAR) nuclear hormone receptors. These findings indicate that the ability of human DCs to present lipid antigens to T cells through expression of CD1 molecules is sensitively regulated by lysophosphatidic acid and cardiolipin in serum, which are ligands that can activate PPAR transcription factors. C1 [Leslie, David S.; Cembrola, Katherine; Townes, Maria A.; Hava, David L.; Roura-Mir, Carme; Moody, D. Branch; Vincent, Michael S.; Brenner, Michael B.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Leslie, David S.; Cembrola, Katherine; Townes, Maria A.; Hava, David L.; Roura-Mir, Carme; Moody, D. Branch; Vincent, Michael S.; Brenner, Michael B.] Harvard Univ, Sch Med, Boston, MA USA. [Dascher, Christopher C.] Mt Sinai Sch Med, Inst Immunol, New York, NY USA. [Hugendubler, Lynne C.; Mueller, Elisabetta] NIDDK, GDDB, Bethesda, MD USA. [Fox, Lisa; Gumperz, Jenny E.] Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Illarionov, Petr A.; Besra, Gurdyal S.] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. [Reynolds, Carol G.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. RP Dascher, CC (reprint author), 1 Gustave Levy Pl,Box 1630, New York, NY 10029 USA. EM dascher@mssm.edu; mbrenner@rics.bwh.harvard.edu RI Roura-Mir, Carme/D-4538-2013; OI Roura-Mir, Carme/0000-0003-0514-337X; Besra, Gurdyal/0000-0002-5605-0395 FU Arthritis National Research Foundation; Pfizer, Inc.; National Institutes of Health [K08AR02171]; Medical Research Council [G9901077, G0400421]; Wellcome Trust [07221/Z/03/Z] FX This research was supported by the Arthritis National Research Foundation (D. S. L.), an ARA Award to D. S. L. sponsored by Pfizer, Inc., the National Institutes of Health (K08AR02171 to D. S. L.), the Medical Research Council (G9901077 and G0400421 to G. S. B.), and the Wellcome Trust (07221/Z/03/Z to G. S. B.). NR 40 TC 35 Z9 36 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 2008 VL 125 IS 3 BP 289 EP 301 DI 10.1111/j.1365-2567.2008.02842.x PG 13 WC Immunology SC Immunology GA 357RS UT WOS:000259864500002 PM 18445008 ER PT J AU Zahid, MSH Udden, SMN Faruque, ASG Calderwood, SB Mekalanos, JJ Faruque, SM AF Zahid, M. Shamim Hasan Udden, S. M. Nashir Faruque, A. S. G. Calderwood, Stephen B. Mekalanos, John J. Faruque, Shah M. TI Effect of Phage on the Infectivity of Vibrio cholerae and Emergence of Genetic Variants SO INFECTION AND IMMUNITY LA English DT Article ID COLONIZATION; ENVIRONMENT; EPIDEMICS; STOOL; WATER AB Seasonal epidemics of cholera in Bangladesh are self-limited in nature, presumably due to phage predation of the causative Vibrio cholerae during the late stage of an epidemic, when cholera patients excrete large quantities of phage in their stools. To further understand the mechanisms involved, we studied the effect of phage on the infectivity and survival of V. cholerae shed in stools. The 50% infectious dose of stool vibrios in infant mice was similar to 10-fold higher when the stools contained a phage (1.8 x 10(3) to 5.7 x 10(6) PFU/ml) than when stools did not contain a detectable phage. In competition assays in mice using a reference strain and phage-negative cholera stools, the infectivity of biofilm-like clumped cells was 3.9- to 115.9-fold higher than that of the corresponding planktonic cells. However, the difference in infectivity of these two cell populations in phage-positive stools was significantly less than that in phage-negative stools (P = 0.0006). Coculture of a phage and V. cholerae or dilutions of phage-positive cholera stools in nutrient medium, but not in environmental water, caused rapid emergence of phage-resistant derivatives of the bacteria, and these derivatives lost their O1 antigen. In cholera stools and in intestinal contents of mice prechallenged with a mixture of V. cholerae and phage, the bacteria remained completely phage susceptible, suggesting that the intestinal environment did not favor the emergence of phage-resistant derivatives that lost the O1 antigen. Our results indicate that phages lead to the collapse of epidemics by modulating the required infectious dose of the bacteria. Furthermore, the dominance of phage-resistant variants due to the bactericidal selective mechanism occurs rarely in natural settings, and the emerging variants are thus unable to sustain the ongoing epidemic. C1 [Zahid, M. Shamim Hasan; Udden, S. M. Nashir; Faruque, A. S. G.; Faruque, Shah M.] ICDDR B, Mol Genet Lab, Dhaka 1212, Bangladesh. [Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Mekalanos, John J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Faruque, SM (reprint author), ICDDR B, Mol Genet Lab, Dhaka 1212, Bangladesh. EM faruque@icddrb.org FU National Institutes of Health [2RO1-GM068851-5, AI070963-01A1, U01-AI58935] FX This research was funded in part by National Institutes of Health grants 2RO1-GM068851-5, AI070963-01A1, and U01-AI58935 under different subagreements between the Harvard Medical School, Massachusetts General Hospital, and the ICDDR, B. The ICDDR, B is supported by countries and agencies which share its concern for the health problems of developing countries. NR 22 TC 33 Z9 33 U1 0 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 NOV PY 2008 VL 76 IS 11 BP 5266 EP 5273 DI 10.1128/IAI.00578-08 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 361YW UT WOS:000260165500052 PM 18794293 ER PT J AU Finfer, S Ranieri, VM Thompson, BT Barie, PS Dhainaut, JF Douglas, IS Gardlund, B Marshall, JC Rhodes, A AF Finfer, Simon Ranieri, V. Marco Thompson, B. Taylor Barie, Philip S. Dhainaut, Jean-Francois Douglas, Ivor S. Gardlund, Bengt Marshall, John C. Rhodes, Andrew TI Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock SO INTENSIVE CARE MEDICINE LA English DT Article DE Severe sepsis; Septic shock; Drotrecogin alfa (activated); Clinical trial methodology; Drug industry-ethics ID INTENSIVE-CARE UNITS; SEVERE SEPSIS; EPIDEMIOLOGY; MULTICENTER; BENEFIT; STATES; MANAGEMENT; HOSPITALS; SAFETY; ADULTS AB The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data. C1 [Finfer, Simon] Univ Sydney, George Inst Int Hlth, Sydney, NSW 2050, Australia. [Ranieri, V. Marco] Univ Turin, Osped S Giovanni Battista Molinette, Turin, Italy. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Barie, Philip S.] Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA. [Dhainaut, Jean-Francois] Paris Descartes Univ, Cochin Port Royal Hosp, Paris, France. [Douglas, Ivor S.] Denver Hlth, Denver, CO USA. [Douglas, Ivor S.] Univ Colorado, Denver, CO 80202 USA. [Gardlund, Bengt] Karolinska Univ Hosp, Dept Infect Dis, S-14186 Stockholm, Sweden. [Marshall, John C.] St Michaels Hosp, Dept Surg, Toronto, ON M5B 1W8, Canada. [Marshall, John C.] St Michaels Hosp, Dept Crit Care Med, Toronto, ON M5B 1W8, Canada. [Rhodes, Andrew] Univ London St Georges Hosp, Dept Intens Care Med & Anaesthesia, London SW17 0QT, England. RP Finfer, S (reprint author), Univ Sydney, George Inst Int Hlth, POB M201,Missenden Rd, Sydney, NSW 2050, Australia. EM sfinfer@george.org.au OI Douglas, Ivor/0000-0002-4541-1431 NR 46 TC 69 Z9 70 U1 0 U2 7 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 NOV PY 2008 VL 34 IS 11 BP 1935 EP 1947 DI 10.1007/s00134-008-1266-6 PG 13 WC Critical Care Medicine SC General & Internal Medicine GA 364AN UT WOS:000260308700001 PM 18839141 ER PT J AU Esteban, A Frutos-Vivar, F Anzueto, A AF Esteban, Andres Frutos-Vivar, Fernando Anzueto, Antonio TI Impact of body weight on critically ill patients: a heavy load!! SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID OBESITY C1 [Esteban, Andres; Frutos-Vivar, Fernando] Hosp Univ Getafe, Inst Salud Carlos III, Serv Cuidados Intens, CIBER Enfermedades Resp, Madrid 28905, Spain. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Mem VA Hosp, San Antonio, TX 78229 USA. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Esteban, A (reprint author), Hosp Univ Getafe, Inst Salud Carlos III, Serv Cuidados Intens, CIBER Enfermedades Resp, Carretera Toledo Km 12,500, Madrid 28905, Spain. EM aesteban@ucigetafe.com OI Frutos-Vivar, Fernando/0000-0002-4648-9636 NR 10 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 2008 VL 34 IS 11 BP 1964 EP 1965 DI 10.1007/s00134-008-1244-z PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 364AN UT WOS:000260308700006 PM 18670755 ER PT J AU Subramanian, B Kuo, F Ada, E Kotyla, T Wilson, T Yoganathan, S Nicolosi, R AF Subramanian, Balajikarthick Kuo, Fonghsu Ada, Earl Kotyla, Tim Wilson, Thomas Yoganathan, Subbiah Nicolosi, Robert TI Enhancement of anti-inflammatory property of aspirin in mice by a nano-emulsion preparation SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Aspirin; Nano-emulsion; Nanotechnology; Anti-inflammatory; Croton oil; Inflammation ID DRUG-DELIVERY; TRANSDERMAL DELIVERY; PARTICLE-SIZE; MOUSE SKIN; CROTON-OIL; EMU OIL; INFLAMMATION; FORMULATION; NANOPARTICLES; NANOEMULSIONS AB Aspirin, a non-steroidal anti-inflammatory drug, widely used for its anti-inflammatory properties is associated with several systemic side effects including gastro-intestinal discomfort. Inflammation can be mediated by pro-inflammatory cytokines and, along with various other host factors eventually give rise to edema at the inflamed site. Because of the adverse side effects oftentimes associated with systemic exposure to aspirin, the aim of the present study was to investigate whether the anti-inflammatory property of aspirin would enhance if delivered as nano-emulsion preparation. Nano-emulsion preparations of aspirin prepared with a Microfluidizer (R) Processor were evaluated in the croton-oil-induced ear edema CD-1 mouse model using ear lobe thickness and the accumulation of specific in situ cytokines as biomarkers of inflammation. The results showed that particle size (90 nm) populations of nano-emulsion preparations of aspirin compared to an aspirin suspension (363 nm), significantly decreased (p<0. 05) ear lobe thickness approximately 2 fold greater than the aspirin suspension. In addition, the aspirin nano-emulsion further reduced the auricular levels of IL-1 alpha (-37%) and TNF alpha (-69%) compared to the aspirin suspension preparation (p<0.05). The reductions in ear lobe thickness were also significantly associated with accumulated tissue levels of IL-l alpha (r=0.5, p<0.009) and TNF alpha (r=0.7, p<0.0004), respectively. In conclusion, these studies indicate that a nano-emulsion preparation of aspirin significantly improved the anti-inflammatory properties of an aspirin suspension in a CD-1 mouse model of induced inflammation. (C) 2008 Elsevier B.V. All rights reserved. C1 [Subramanian, Balajikarthick; Kuo, Fonghsu; Kotyla, Tim; Wilson, Thomas; Nicolosi, Robert] Univ Massachusetts, Ctr Hlth & Dis Res, Lowell, MA 01854 USA. [Subramanian, Balajikarthick; Kuo, Fonghsu; Nicolosi, Robert] Univ Massachusetts, Biomed Engn & Biotechnol Program, Lowell, MA 01854 USA. [Ada, Earl] Univ Massachusetts, Mat Characterizat Lab, Lowell, MA 01854 USA. [Yoganathan, Subbiah] Forsyth Inst, Boston, MA USA. RP Nicolosi, R (reprint author), Univ Massachusetts, Ctr Hlth & Dis Res, 3 Solomt Way, Lowell, MA 01854 USA. EM Robert_Nicolosi@uml.edu OI Wilson, Thomas/0000-0001-8363-4356 NR 48 TC 18 Z9 20 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD NOV PY 2008 VL 8 IS 11 BP 1533 EP 1539 DI 10.1016/j.intimp.2008.06.009 PG 7 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 361KF UT WOS:000260125800006 PM 18625344 ER PT J AU Miao, JY Mu, D Ergel, B Singavarapu, R Duan, ZF Powers, S Oliva, E Orsulic, S AF Miao, Jiangyong Mu, David Ergel, Burce Singavarapu, Rajasekhar Duan, Zhenfeng Powers, Scott Oliva, Esther Orsulic, Sandra TI Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE desmosome; hepsin; ovarian cancer; serine protease ID HEPATOCYTE GROWTH-FACTOR; TRANSMEMBRANE SERINE-PROTEASE; DIFFERENTIALLY EXPRESSED GENE-14; BENIGN PROSTATIC HYPERPLASIA; RENAL-CELL CARCINOMA; MICE DEFICIENT; INTERMEDIATE-FILAMENTS; FACTOR-VII; CLONING; LIVER AB Hepsin is a serine protease that is widely expressed in different tissues and cell types, most prominently in the normal liver and kidney. Overexpression of hepsin has been associated with prostate cancers, ovarian cancers and renal cell carcinomas. The physiological functions of hepsin in normal tissues and tumors are poorly understood. To gain insight into its function in ovarian cancer, we analyzed the expression and subcellular localization of hepsin protein in ovarian cancer cell lines and tumors. We showed that the membrane-associated hepsin protein is present at desmosomal junctions, where it colocalizes with its putative proteolytic substrate hepatocyte growth factor. Consistent with the growing evidence that desmosomal junctions and their constituents play a role in cancer progression, we demonstrated that overexpression of hepsin promotes ovarian tumor growth in a mouse model. The ability of ectopic hepsin to induce tumor growth in mice is abrogated by the mutation of 3 critical residues in the catalytic domain, thus implicating the enzymatic activity of hepsin in promoting tumor progression. (c) 2008 Wiley-Liss, Inc. C1 [Miao, Jiangyong; Ergel, Burce; Singavarapu, Rajasekhar; Orsulic, Sandra] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Miao, Jiangyong; Ergel, Burce; Singavarapu, Rajasekhar; Orsulic, Sandra] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Miao, Jiangyong; Oliva, Esther; Orsulic, Sandra] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Mu, David; Powers, Scott] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Duan, Zhenfeng] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Oliva, Esther; Orsulic, Sandra] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Orsulic, S (reprint author), Cedars Sinai Med Ctr, Womens Canc Res Inst, 8700 Beverly Blvd,Suite 290W, Los Angeles, CA 90048 USA. EM orsulics@cshs.org RI Mu, David/E-8933-2011 OI Mu, David/0000-0002-7762-0182 FU Department of Defense OCRP Training Program Award [DAMD17-03-1-0161]; Joan's Legacy Foundation; NIH [RO1CA103924]; Ovarian Cancer Research Fund (OCRF) Program Project Development Grant FX Department of Defense OCRP Training Program Award; Grant number: DAMD17-03-1-0161; Grant sponsor: Joan's Legacy Foundation; Grant sponsor: NIH; Grant number: RO1CA103924; Grant sponsor: Ovarian Cancer Research Fund (OCRF) Program Project Development Grant. NR 48 TC 21 Z9 23 U1 1 U2 1 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 NOV 1 PY 2008 VL 123 IS 9 BP 2041 EP 2047 DI 10.1002/ijc.23726 PG 7 WC Oncology SC Oncology GA 357HE UT WOS:000259836100008 PM 18726901 ER PT J AU Mendez, MF Licht, EA Saul, RE AF Mendez, Mario F. Licht, Eliot A. Saul, Ronald E. TI The Frontal Systems Behavior Scale in the evaluation of dementia SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID FRONTOTEMPORAL DEMENTIA C1 [Mendez, Mario F.; Licht, Eliot A.; Saul, Ronald E.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu NR 5 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD NOV PY 2008 VL 23 IS 11 BP 1203 EP 1204 DI 10.1002/gps.2019 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 371OS UT WOS:000260841300016 PM 18395885 ER PT J AU Matulonis, UA Kornblith, A Lee, H Bryan, J Gibson, C Wells, C Lee, J Sullivan, L Penson, R AF Matulonis, U. A. Kornblith, A. Lee, H. Bryan, J. Gibson, C. Wells, C. Lee, J. Sullivan, L. Penson, R. TI Long-term adjustment of early-stage ovarian cancer survivors SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE cancer survivor; early-stage ovarian cancer ID QUALITY-OF-LIFE; ADVANCED MULLERIAN MALIGNANCIES; CLINICAL-TRIALS; BREAST-CANCER; HOPELESSNESS; ONCOLOGY; HEALTH; CHEMOTHERAPY; PREDICTORS; DISTRESS AB Matulonis UA, Kornblith A, Lee H, Bryan J, Gibson C, Wells C, Lee J, Sullivan L, Penson R. Long-term adjustment of early-stage ovarian cancer survivors. Int J Gynecol Cancer 2008;18:1183-1193. The objectives of this study were to describe the quality of life (QOL), consequences of treatment, complementary therapy use, and factors correlating with psychologic state in 58 survivors of early-stage ovarian cancer since little is known about the QOL of early-stage ovarian cancer survivors. Survivors were interviewed using standardized measures to assess physical, psychologic, social, and sexual functioning; impact of cancer on socioeconomic status; and complementary therapy use. Survivors reported good physical QOL scores and few unmet needs. However, menopausal symptoms and negative impact on sexuality were reported. Less than 10% of survivors reported either an interest in sex or were sexually active. Psychologic assessment yielded a subset of 26% of patients with scores suggestive of posttraumatic stress disorder (PTSD) and 40% of survivors scored below the norm on the Mental Health Inventory-17 Survey. One third of patients required treatment for family/personal problems and took antianxiety medications. About 56% of survivors reported fear of cancer recurrence and 59% reported anxiety when their CA125 is tested. Better mental health was significantly related to less fatigue (Functional Assessment of Cancer Therapy [FACT]-fatigue, r = 0.61, P < 0.0001), less pain (European Organisation for Research and Treatment of Cancer [EORTC], r = -0.54, P < 0.0001), fewer stressful life events (Life Event Scale, r = -0.44, P > 0.001), and greater social support (MOS Social Support Survey, r = 0.41, P < 0.01). Early-stage ovarian cancer survivors had few physical complaints and unmet needs, but psychologic distress was evident in a subset of survivors; the majority of survivors reported sexual dysfunction. These results indicate the need for intervention and improved distress screening in the early-stage ovarian cancer population. C1 [Matulonis, U. A.; Kornblith, A.; Bryan, J.; Lee, J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lee, H.; Gibson, C.; Wells, C.; Sullivan, L.; Penson, R.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ursula_matulonis@dfci.harvard.edu NR 38 TC 52 Z9 52 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV-DEC PY 2008 VL 18 IS 6 BP 1183 EP 1193 DI 10.1111/j.1525-1438.2007.01167.x PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 371HX UT WOS:000260823500004 PM 18217977 ER PT J AU Andronesi, OC Blekas, KD Mintzopoulos, D Astrakas, L Black, PM Tzika, AA AF Andronesi, Ovidiu C. Blekas, Konstantinos D. Mintzopoulos, Dionyssios Astrakas, Loukas Black, Peter M. Tzika, A. Aria TI Molecular classification of brain tumor biopsies using solid-state magic angle spinning proton magnetic resonance spectroscopy and robust classifiers SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE brain/CNS cancers; tumor biomarkers; ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy; support vector machines; neural networks ID H-1 MR SPECTRA; PRIMITIVE NEUROECTODERMAL TUMOR; GENE-EXPRESSION SIGNATURES; ARTIFICIAL NEURAL-NETWORKS; SUPPORT-VECTOR-MACHINES; SHORT ECHO TIME; IN-VIVO; EX-VIVO; PATTERN-RECOGNITION; NMR-SPECTROSCOPY AB Brain tumors are one of the leading causes of death in adults with cancer; however, molecular classification of these tumors with in vivo magnetic resonance spectroscopy (MRS) is limited because of the small number of metabolites detected. In vitro MRS provides highly informative biomarker profiles at higher fields, but also consumes the sample so that it is unavailable for subsequent analysis. In contrast, ex vivo high-resolution magic angle spinning (HRMAS) MRS conserves the sample but requires large samples and can pose technical challenges for producing accurate data, depending on the sample testing temperature. We developed a novel approach that combines a two-dimensional (213), solid-state, HRMAS proton ((1)H) NMR method, TOBSY (total through-bond spectroscopy), which maximizes the advantages of HRMAS and a robust classification strategy. We used similar to 2 mg of tissue at -8 degrees C from each of 55 brain biopsies, and reliably detected 16 different biologically relevant molecular species. We compared two classification strategies, the support vector machine (SVM) classifier and a feed-forward neural network using the Levenberg-Marquardt back-propagation algorithm. We used the minimum redundancy/maximum relevance (MRMR) method as a powerful feature-selection scheme along with the SVM classifier. We suggest that molecular characterization of brain tumors based on highly informative 2D MRS should enable us to type and prognose even inoperable patients with high accuracy in vivo. C1 [Tzika, A. Aria] Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Astrakas, Loukas; Tzika, A. Aria] Harvard Univ, Dept Surg, NMR Surg Lab, Sch Med, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Tzika, A. Aria] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Blekas, Konstantinos D.] Univ Ioannina, Dept Comp Sci, GR-45110 Ioannina, Greece. [Astrakas, Loukas] Univ Ioannina, Dept Med Phys, GR-45110 Ioannina, Greece. [Black, Peter M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP Andronesi, OC (reprint author), Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu RI Astrakas, Loukas/F-5918-2011 FU Departments of Surgery and Radiology FX The study was supported in part by discretional funds to A. Aria Tzika. The authors thank the Departments of Surgery and Radiology at Massachusetts General Hospital, as well as Neurosurgery and Pathology at Brigham and Women's Hospital Boston for supporting this study. We also thank Drs Ann Power Smith and Kathryn Edmondson of Write Science Right for editorial assistance. NR 72 TC 13 Z9 13 U1 1 U2 11 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 2008 VL 33 IS 5 BP 1017 EP 1025 DI 10.3892/ijo_00000090 PG 9 WC Oncology SC Oncology GA 367JG UT WOS:000260547700012 PM 18949365 ER PT J AU Halpin, C Sims, K AF Halpin, Chris Sims, Katherine TI Twenty years of audiology in a patient with Norrie disease SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Norrie disease; Hearing loss; Hearing aids ID MODEL AB Objective: To describe disease progression and treatment outcomes over a 20-year period (ages 5-25) in a young man with Norrie disease (occuloacousticocerebral dysplasia), ND; OMIM #310600. Affected individuals are born blind and develop progressive sensory loss with onset in adolescence. This disease is X-linked and has been associated with mutations of the NDP gene (Xp11.4). Methods: The patient was followed using repeated audiograms, as well as reports of educational progress and hearing aid use. The specific mutation was found by molecular analysis. Results: The patient demonstrated progressive sensory toss with good preservation of word recognition. The toss was initially high frequency and asymmetric in adolescence and became more severe, more symmetric and affected practically all frequencies by the end of childhood. Educational progress was affected by the cognitive effects of the syndrome, and hearing aid use was very effective. Conclusions: A bilateral progressive sensory loss with good preservation of word recognition was documented in detail. The residual word recognition supported good use of hearing aids in this case. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Halpin, Chris] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Sims, Katherine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Halpin, C (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. EM cfhalpin@meei.harvard.edu NR 15 TC 6 Z9 6 U1 0 U2 0 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 NOV PY 2008 VL 72 IS 11 BP 1705 EP 1710 DI 10.1016/j.ijporl.2008.08.007 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 367JR UT WOS:000260548800015 PM 18817988 ER PT J AU Hurwitz, MD Halabi, S Ou, SS McGinnis, LS Keuttel, MR DiBiase, SJ Small, EJ AF Hurwitz, Mark D. Halabi, Susan Ou, San-San McGinnis, Lamar S. Keuttel, Michael R. DiBiase, Steven J. Small, Eric J. TI Combination external beam radiation and brachytherapy boost with androgen suppression for treatment of intermediate-risk prostate cancer: An initial report of CALGB 99809 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation; brachytherapy; prostate; clinical trial; brachytherapy boost ID CLINICALLY LOCALIZED ADENOCARCINOMA; GASTROINTESTINAL TOXICITY; RECTAL COMPLICATIONS; DOSE-ESCALATION; RADIOTHERAPY; THERAPY; TRIAL; IMPLANTATION; MORBIDITY; CARCINOMA AB Purpose:Transperineal prostate brachytherapy (TPPB) can be used with external beam radiation therapy (EBRT) to provide a high-dose conformal boost to the prostate. The results of a multicenter Phase 11 trial assessing safety of combination of EBRT and TPPB boost with androgen suppression (AST) in treatment of intermediate-risk prostate cancer are present here. Materials and Methods: Patients had intermediate-risk prostate cancer. Six months of AST was administered. ERRT to the prostate and seminal vesicles was administered to 45Gy followed by TPPB using either I-125 or Pd-103 to deliver an additional 100Gy or 90Gy. Toxicity was graded using the National Cancer Institute CTC version. 2 and the Radiation Therapy Oncology Group late radiation morbidity scoring systems. Results: Sixty-three patients were enrolled. Median follow-up was 38 months. Side effects of AST including sexual dysfunction and vasomotor symptoms were commonly observed. Apart from erectile dysfunction, short-term Grade 2 and 3 toxicity was noted in 21 % and 7%, primarily genitourinary related. Long-term Grade 2 and 3 toxicities were noted in 13% and 3 %. Two patients had Grade 3 dysuria that resolved with longer follow-up. The most common Grade 2 long-term toxicity was urinary frequency (5%). No biochemical or clinical evidence of progression was noted for the entire cohort. Conclusions: In a cooperative group setting, combination EBRT and TPPB with 6 months of AST was generally well tolerated with expected genitourinary and gastrointestinal toxicities. Further follow-up will be required to fully assess long-term toxicity and cancer control. (C) 2008 Elsevier Inc. C1 [Hurwitz, Mark D.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Halabi, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Ou, San-San] Duke Univ, Med Ctr Durham, CALGB Stat Ctr, Durham, NC 27706 USA. [McGinnis, Lamar S.] SE Canc Control Consortium, Winston Salem, NC USA. [Keuttel, Michael R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [DiBiase, Steven J.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Small, Eric J.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Hurwitz, MD (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI,L2, Boston, MA 02115 USA. EM mhurwitz@lroc.harvard.edu FU NCI [CA33601] FX Supported by NCI Grant CA33601. NR 20 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2008 VL 72 IS 3 BP 814 EP 819 DI 10.1016/j.ijrobp.2008.01.010 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 358CN UT WOS:000259894300026 PM 18407435 ER PT J AU Stewart, AJ Cormack, RA Lee, H Xiong, L Hansen, JL O'Farrell, DA Viswanathan, AN AF Stewart, Alexandra J. Cormack, Robert A. Lee, Hang Xiong, Li Hansen, Jorgen L. O'Farrell, Desmond A. Viswanathan, Akila N. TI Prospective clinical trial of bladder filling and three-dimensional dosimetry in high-dose-rate vaginal cuff brachytherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE vaginal cuff brachytherapy; Computed tomography bladder dosimetry ID RATE INTRACAVITARY BRACHYTHERAPY; CERVIX CANCER BRACHYTHERAPY; IC ENDOMETRIAL CANCER; COMPUTED-TOMOGRAPHY; PROSTATE-CANCER; INTRAVAGINAL BRACHYTHERAPY; VAULT BRACHYTHERAPY; VOLUME PARAMETERS; REFERENCE-POINT; CARCINOMA AB Purpose: To investigate the effect of bladder filling on dosimetry and to determine the best bladder dosimetric parameter for vaginal cuff brachytherapy. Methods and Materials: In this prospective clinical trial, a total of 20 women underwent vaginal cylinder high-dose-rate brachytherapy. The bladder was full for Fraction 2 and empty for Fraction 3. Dose-volume histogram and dose-surface histogram values were generated for the bladder, rectum, and urethra. The midline maximal bladder point (MBP) and the midline maximal rectal point were recorded. Paired t tests, Pearson correlations, and regression analyses were performed. Results: The volume and surface area of the irradiated bladder were significantly smaller when the bladder was empty than when full. Of the several dose-volume histogram and dose-surface histogram parameters evaluated, the bladder maximal dose received by 2 cm(3) of tissue, volume of bladder receiving >= 50% of the dose, volume of bladder receiving >= 70% of the dose, and surface area of bladder receiving >= 50% of the dose significantly predicted for the difference between the empty vs. full filling state. The volume of bladder receiving >= 70% of the dose and the maximal dose received by 2 cm(3) of tissue correlated significantly with the MBP Bladder filling did not after the volume or surface area of the rectum irradiated. However, an empty bladder did result in the nearest point of bowel being significantly closer to the vaginal cylinder than when the bladder was full. Conclusions: Patients undergoing vaginal cuff brachytherapy treated with an empty bladder have a lower bladder dose than those treated with a full bladder. The MBP correlated well with the volumetric assessments of bladder dose and provided a noninvasive method for reporting the MBP dose using three-dimensional imaging. The MBP can therefore be used as a surrogate for complex dosimetry in the clinic. (C) 2008 Elsevier Inc. C1 [Stewart, Alexandra J.; Cormack, Robert A.; Xiong, Li; Hansen, Jorgen L.; O'Farrell, Desmond A.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat Sci, Boston, MA USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu OI Viswanathan, Akila/0000-0002-2003-0392; Cormack, Robert/0000-0001-5553-9984 FU NCI NIH HHS [K07 CA117979-01, K07 CA117979-04, K07 CA117979-02, K07 CA117979, K07 CA117979-03] NR 37 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2008 VL 72 IS 3 BP 843 EP 848 DI 10.1016/j.ijrobp.2008.01.041 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 358CN UT WOS:000259894300030 PM 18395360 ER PT J AU Wong, JLS Taghian, AG Bellon, JR Keshaviah, A Smith, BL Winer, EP Silver, B Harris, JR AF Wong, Julia S. Taghian, Alphonse G. Bellon, Jennifer R. Keshaviah, Aparna Smith, Barbara L. Winer, Eric P. Silver, Barbara Harris, Jay R. TI Tangential radiotherapy without axillary surgery in early-stage breast cancer: Results of a prospective trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast cancer; radiotherapy; axillary nodes; high tangents ID LYMPH-NODE BIOPSY; LUMPECTOMY PLUS TAMOXIFEN; WOMEN 70 YEARS; RADIATION-THERAPY; FOLLOW-UP; CONSERVATIVE SURGERY; SENTINEL; IRRADIATION; DISSECTION; OLDER AB Purpose: To determine the risk of regional-nodal recurrence in patients with early-stage, invasive breast cancer, e axillary nodes, who were treated with breast-conserving surgery "high tangential" breast with clinically negative radiotherapy, and hormonal therapy, without axillary surgery or the use of a separate nodal radiation field. Methods and Materials: Between September 1998 and November 2(K)3,74 patients who were >= 55 years of age with Stag I-II clinically node-negative, hormone-receptor-positive breast cancer underwent tumor excision to negative margins without axillary surgery as a part of a multi-institutional prospective study. Postoperatively, all underwent high-tangential, whole-breast radiotherapy with a boost to the tumor bed, followed by 5 years of hormonal therapy. Results: For the 74 patients enrolled, the median age was 74.5 years, and the median pathologic tumor size was 1.2 cm. Lymphatic vessel invasion was present in 5 patients (7%). At it median follow-up of 52 months, no regional-nodal failures or ipsilateral breast recurrences had been identified (95% confidence interval, Eight patients died, one of metastatic disease and seven of other causes. Conclusion: In this select group of mainly older patients with early-stage hormone-responsive breast cancer and clinically negative axillary nodes, treatment with high-tangential breast radiotherapy and hormonal therapy, without axillary surgery, yielded a low regional recurrence rate. Such patients might he spared more extensive axillary treatment (axillary surgery, including sentinel node biopsy, or a separate nodal radiation field), with its associated time, expense, and morbidity. (C) 2008 Elsevier Inc. C1 [Wong, Julia S.; Bellon, Jennifer R.; Silver, Barbara; Harris, Jay R.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Keshaviah, Aparna] Dana Farber Brigham & Womens Canc Ctr, Dept Biostat & Computat Biol, Boston, MA USA. [Winer, Eric P.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA USA. [Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Smith, Barbara L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Wong, JLS (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM jwong@lroc.harvard.edu NR 16 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2008 VL 72 IS 3 BP 866 EP 870 DI 10.1016/j.ijrobp.2008.01.031 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 358CN UT WOS:000259894300033 PM 18394815 ER PT J AU She, HC Nakazawa, T Matsubara, A Connolly, E Hisatomi, T Noda, K Kim, I Gragoudas, ES Miller, JW AF She, Haicheng Nakazawa, Toru Matsubara, Akihisa Connolly, Edward Hisatomi, Toshio Noda, Kousuke Kim, Ivana Gragoudas, Evangelos S. Miller, Joan W. TI Photoreceptor Protection after Photodynamic Therapy Using Dexamethasone in a Rat Model of Choroidal Neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; RANDOMIZED CLINICAL-TRIAL; MACULAR DEGENERATION; VERTEPORFIN THERAPY; TUMOR-GROWTH; IN-VIVO; BENZOPORPHYRIN; ANGIOGENESIS; RETINA; INJECTION AB PURPOSE. To study whether corticosteroids protect photoreceptors when combined with photodynamic therapy (PDT) in a laser-induced model of choroidal neovascularization (CNV). METHODS. PDT was performed in 36 Brown-Norway rats 2 weeks after laser induction of CNV. The expressional change of several cytokines and chemokines in the CNV lesions after PDT was measured by real-time PCR in combination with laser-capture microdissection. Immunostaining for monocyte chemoattractant protein (MCP)-1, C-C chemokine receptor 2(CCR2), interleukin (IL)-1 beta, and myeloperoxidase(MPO) were performed. To study the effect of corticosteroids in combination with PDT, either dexamethasone (100 mg/kg) or control was injected intraperitoneally 1 hour before PDT. Animals were killed 24 hours or 1 week after PDT. CNV was examined by fluorescein angiography and choroidal flatmount. Photoreceptor degeneration was evaluated by TUNEL assay. RESULTS. MCP-1 and IL-1 beta was increased in CNV lesions 24 hours after PDT. CCR2 was also expressed in laser-induced CNV but did not increase after PDT. Twenty-four hours after PDT, MPO-positive cells were noted in the CNV lesions. Dexamethasone-treated animals had significantly fewer TUNEL-positive cells in the photoreceptor layer than did the control animals (P < 0.05) after PDT. Fluorescein angiographic grading of CNV closure 6 days after PDT showed a closure rate in the dexamethasone-treated group of 31% (15/48 lesions) compared to 10% (4/42 lesions) in the control group (P < 0.05). CNV size was significantly smaller in the dexamethasonetreated group 1 week after PDT compared with the control (P < 0.05). CONCLUSIONS. Systemic administration of dexamethasone combined with PDT reduces photoreceptor apoptosis, increases angiographic closure, and reduces CNV size compared with PDT alone in a rat model. (Invest Ophthalmol Vis Sci. 2008;49:5008-5014) DOI: 10.1167/iovs.07-1154 C1 [She, Haicheng; Nakazawa, Toru; Matsubara, Akihisa; Connolly, Edward; Hisatomi, Toshio; Noda, Kousuke; Kim, Ivana; Gragoudas, Evangelos S.; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis & Laser Labs,Dept Ophthalmol, Boston, MA 02114 USA. [She, Haicheng] Capital Med Univ, Beijing Tongren Eye Ctr, Beijing Tongren Hosp, Beijing, Peoples R China. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis & Laser Labs,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu OI Hisatomi, Toshio/0000-0003-2552-9595 FU Neovascular Research Fund; National Eye Institute [P30 EY014104]; National Institute on Aging [AI050775]; Alcon Research Institute Award; Massachusetts Lions Eye Research Foundation; AMD Fund FX Supported by the Neovascular Research Fund; National Eye Institute Core Grant P30 EY014104; National Institute on Aging Grant AI050775; Alcon Research Institute Award; Massachusetts Lions Eye Research Foundation; Research to Prevent Blindness; Marion W. and Edward F. Knight AMD Fund. NR 41 TC 10 Z9 10 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 NOV PY 2008 VL 49 IS 11 BP 5008 EP 5014 DI 10.1167/iovs.07-1154 PG 7 WC Ophthalmology SC Ophthalmology GA 366RX UT WOS:000260502200043 PM 18421085 ER PT J AU Gangnon, RE Davis, MD Hubbard, LD Aiello, LM Chew, EY Ferris, FL Fisher, MR AF Gangnon, Ronald E. Davis, Matthew D. Hubbard, Larry D. Aiello, Lloyd M. Chew, Emily Y. Ferris, Frederick L., III Fisher, Marian R. CA Early Treatment Diabetic Retinopa TI A Severity Scale for Diabetic Macular Edema Developed from ETDRS Data SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; RETINOPATHY AB PURPOSE. To develop a severity scale for diabetic macular edema (DME) and to assess relationships between severity and duration of DME and visual acuity (VA). METHODS. From the Early Treatment Diabetic Retinopathy Study (ETDRS), mean baseline VA scores were tabulated for 7422 eyes cross-classified by (1) location of retinal thickening (RT) and its area within 1 disc diameter of the macular center, and (2) degree of RT at the center. Adjacent (row, column, and off-diagonal) cells with the greatest similarity in baseline VA (mean and SD) based on a Gaussian (normal) likelihood were merged. An initial eight-step scale was chosen using the Schwarz criterion (Bayesian information criterion; BIC) and was revised based on clinical judgment to nine steps. Relationships between baseline VA and other photographic and fluorescein angiographic characteristics were examined singly and in combination with the scale. RESULTS. Modeling baseline VA as a function of the nine-step scale yielded an R-2 of 38.0%, compared with 38.4% using the full cross-classification of these variables. Addition of each of the other baseline characteristics changed the adjusted R2 for the combination very little. Between scale levels 1A and 5B mean (SD) VA decreased from 86.8 (5.8) letters to 59.8 (13.6) letters. In a model of change in VA as a function of time spent at each DME severity level, VA loss increased progressively from 1 letter per year at level 2 to 17 letters per year at level 5B. CONCLUSIONS. The scale facilitates documentation of the relationship of severity and duration of DME with VA. (Invest Ophthalmol Vis Sci. 2008;49:5041-5047) DOI:10.1167/iovs.08-2231 C1 [Davis, Matthew D.; Hubbard, Larry D.] Univ Wisconsin, FPRC, Dept Ophthalmol & Visual Sci, Madison, WI 53711 USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53711 USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Stat, Madison, WI 53711 USA. [Fisher, Marian R.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53711 USA. [Aiello, Lloyd M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Chew, Emily Y.; Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA. RP Hubbard, LD (reprint author), Univ Wisconsin, FPRC, Dept Ophthalmol & Visual Sci, Pk W 1, Madison, WI 53711 USA. EM hubbard@rc.ophth.wisc.edu FU National Eye Institute [R03 EY1029-01] FX Supported by Grant R03 EY1029-01 from the National Eye Institute. NR 13 TC 19 Z9 20 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 NOV PY 2008 VL 49 IS 11 BP 5041 EP 5047 DI 10.1167/iovs.08-2231 PG 7 WC Ophthalmology SC Ophthalmology GA 366RX UT WOS:000260502200047 PM 18539929 ER PT J AU Feuchtner, GM Dichtl, W Bonatti, JO Jodocy, D Muller, S Hintringer, F Gradl, J Klauser, A Cury, RC AF Feuchtner, Gudrun M. Dichtl, Wolfgang Bonatti, Johannes O. Jodocy, Daniel Mueller, Silvana Hintringer, Florian Gradl, Johannes Klauser, Andrea Cury, Ricardo C. TI Diagnostic Accuracy of Cardiac 64-Slice Computed Tomography in Detecting Atrial Thrombi Comparative Study With Transesophageal Echocardiography and Cardiac Surgery SO INVESTIGATIVE RADIOLOGY LA English DT Article DE cardiac multidetector computed tomography; CT; MDCT; left atrial thrombi; echocardiography; atrial fibrillation ID APPENDAGE FILLING DEFECTS; SPONTANEOUS ECHO CONTRAST; CORONARY-ARTERY-DISEASE; DUAL-SOURCE CT; HELICAL CT; FIBRILLATION; ANGIOGRAPHY; MANAGEMENT; REDUCTION; ABLATION AB Objectives: Atrial thrombi are a potential source for cerebral and peripheral emboli. Objective of this study was to evaluate the diagnostic accuracy of 64-slice cardiac computed tomography (CT) for detection of atrial thrombi in comparison with transesophageal echocardiography (TEE) and cardiac surgery. Material and Methods: Sixty-four patients were examined with ECG-gated multidetector CT coronary or pulmonary vein angiography. All patients underwent TEE. Cardiac surgery was performed in 31 patients. The Hounsfield units (HU) of atrial lesions were measured. Results: The diagnostic accuracy of 64-slice CT for the detection of atrial thrombi was 77%: sensitivity 100% (9/9), specificity 73% (40/55), positive predictive value (PPV) 38% (9/24), and negative predictive value (NPV) 100% (40/40). All 15 false positive (FP) findings by CT were located in the left atrial appendage (LAA). Four characteristic imaging features suggesting incomplete filling of the LAA were noted in FP: "hypostatic layering," 5115 (33%); "flow phenomenon," 9/15 (60%); "HU-run-off," 8/15 (53%); higher intralesional HU in FP when compared with thrombi (153.8 HU +/- 71 vs. 46.6 HU +/- 10; P < 0.0001). The diagnostic accuracy of CT in detecting atrial thrombi improved significantly (P = 0.03) to 86% after defining "typical filling defects" as "flow phenomenon/> 180 HU" (sensitivity 100%; specificity 84%; PPV 50%; NPV 100%). On receiver operating curve (ROC) analysis, a threshold of 60.7 HU showed a specificity of 100% and a sensitivity of 86.7% to distinguish between FP and thrombi. Conclusions: Cardiac ECG-gated 64-slice CT is accurate to exclude atrial thrombi, which can be applied eg, in patients before radiofrequency (RF) ablation. Left atrial appendage "filling defects" cause a high number of false positive findings, and there are radiologic features, which are helpful to differentiate them from true thrombi. C1 [Feuchtner, Gudrun M.; Gradl, Johannes; Klauser, Andrea] Innsbruck Med Univ, Clin Dept Radiol 2, A-6020 Innsbruck, Austria. [Dichtl, Wolfgang; Jodocy, Daniel; Mueller, Silvana; Hintringer, Florian] Innsbruck Med Univ, Dept Clin Cardiol, A-6020 Innsbruck, Austria. [Bonatti, Johannes O.] Innsbruck Med Univ, Clin Dept Cardiac Surg, A-6020 Innsbruck, Austria. [Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Feuchtner, GM (reprint author), Innsbruck Med Univ, Clin Dept Radiol 2, Anichstr 35, A-6020 Innsbruck, Austria. EM Gudrun.Feuchtner@i-med.ac.at NR 34 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 2008 VL 43 IS 11 BP 794 EP 801 DI 10.1097/RLI.0b013e318184cd6c PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364SF UT WOS:000260354900006 PM 18923259 ER PT J AU Tearney, GJ Waxman, S Shishkov, M Vakoc, BJ Suter, MJ Freilich, MI Desjardins, AE Oh, WY Bartlett, LA Rosenberg, M Bouma, BE AF Tearney, Guillermo J. Waxman, Sergio Shishkov, Milen Vakoc, Benjamin J. Suter, Melissa J. Freilich, Mark I. Desjardins, Adrien E. Oh, Wang-Yul Bartlett, Lisa A. Rosenberg, Mireille Bouma, Brett E. TI Three-Dimensional Coronary Artery Microscopy by Intracoronary Optical Frequency Domain Imaging SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE intravascular imaging; coronary imaging; optical coherence tomography; stents AB OBJECTIVES We present the first clinical experience with intracoronary optical frequency domain imaging (OFDI) in human patients. BACKGROUND Intracoronary optical coherence tomography (OCT) is a catheter-based optical imaging modality that is capable of providing microscopic (similar to 7-mu m axial resolution, similar to 30-mu m transverse resolution), cross-sectional images of the coronary wall. Although the use of OCT has shown substantial promise for imaging coronary microstructure, blood attenuates the OCT signal, necessitating prolonged, proximal occlusion to screen long arterial segments. OFDI is a second-generation form of OCT that is capable of acquiring images at much higher frame rates. The increased speed of OFDI enables rapid, 3-dimensional imaging of long coronary segments after a brief, nonocclusive saline purge. METHODS Volumetric OFDI images were obtained in 3 patients after intracoronary stent deployment. Imaging was performed in the left anterior descending and right coronary arteries with the use of a nonocclusive saline purge rates ranging from 3 to 4 ml/s and for purge durations of 3 to 4 s. After imaging, the OFDI datasets were segmented using previously documented criteria and volume rendered. RESULTS Good visualization of the artery wall was obtained in all cases, with clear viewing lengths ranging from 3.0 to 7.0 cm at pullback rates ranging from 5 to 20 mm/s. A diverse range of microscopic features were identified in 2 and 3 dimensions, including thin-capped fibroatheromas, calcium, macrophages, cholesterol crystals, bare stent struts, and stents with neointimal hyperplasia. There were no complications of the OFDI procedure. CONCLUSIONS Our results demonstrate that OFDI is a viable method for imaging the microstructure of long coronary segments in patients. Given its ability to provide microscopic information in a practical manner, this technology may be useful for studying human coronary pathophysiology in vivo and as a clinical tool for guiding the management of coronary artery disease. (J Am Coll Cardiol Img 2008; 1:752-61) (C) 2008 by the American College of Cardiology Foundation C1 [Tearney, Guillermo J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Shishkov, Milen; Vakoc, Benjamin J.; Suter, Melissa J.; Desjardins, Adrien E.; Oh, Wang-Yul; Bartlett, Lisa A.; Bouma, Brett E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Waxman, Sergio; Freilich, Mark I.] Lahey Clin Fdn, Dept Cardiol, Burlington, MA USA. [Tearney, Guillermo J.; Desjardins, Adrien E.; Bouma, Brett E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Waxman, Sergio] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,BAR 703, Boston, MA 02114 USA. EM gtearney@partners.org RI Oh, Wang-Yuhl/C-2055-2011 FU NIH [5R01HL076398]; Terumo Corporation FX This study was funded by the NIH contract 5R01HL076398. Terumo Corporation sponsors nonclinical OFDI research in the laboratory of Drs. Tearney and Bouma and has a technology-licensing arrangement with Massachusetts General Hospital. NR 43 TC 160 Z9 165 U1 0 U2 17 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 NOV PY 2008 VL 1 IS 6 BP 752 EP 761 DI 10.1016/j.jcmg.2008.06.007 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V13EM UT WOS:000207650100008 PM 19356512 ER PT J AU Truong, QA Singh, JP Cannon, CP Sarwar, A Nasir, K Auricchio, A Faletra, FF Sorgente, A Conca, C Moccetti, T Handschumacher, M Brady, TJ Hoffmann, U AF Truong, Quynh A. Singh, Jagmeet P. Cannon, Christopher P. Sarwar, Ammar Nasir, Khurram Auricchio, Angelo Faletra, Francesco F. Sorgente, Antonio Conca, Cristina Moccetti, Tiziano Handschumacher, Mark Brady, Thomas J. Hoffmann, Udo TI Quantitative Analysis of Intraventricular Dyssynchrony Using Wall Thickness by Multidetector Computed Tomography SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE imaging; tomography; heart failure; pacing; dyssynchrony AB OBJECTIVES We sought to determine the feasibility of cardiac computed tomography (CT) to detect significant differences in the extent of left ventricular dyssynchrony in heart failure (HF) patients with wide QRS, HF patients with narrow QRS, and age-matched controls. BACKGROUND The degree of mechanical dyssynchrony has been suggested as a predictor of response to cardiac resynchronization therapy. There have been no published reports of dyssynchrony assessment with the use of CT. METHODS Thirty-eight subjects underwent electrocardiogram-gated contrast-enhanced 64-slice multidetector CT. The left ventricular endocardial and epicardial boundaries were delineated from short-axis images reconstructed at 10% phase increments of the cardiac cycle. Global and segmental CT dyssynchrony metrics that used changes in wall thickness, wall motion, and volume over time were assessed for reproducibility. We defined a global metric using changes in wall thickness as the dyssynchrony index (DI). RESULTS The DI was the most reproducible metric (interobserver and intraobserver intraclass correlation coefficients >= 0.94, p < 0.0001) and was used to determine differences between the 3 groups: HF-wide QRS group (ejection fraction [EF] 22 +/- 8%, QRS 163 +/- 28 ms), HF-narrow QRS (EF 26 +/- 7%, QRS 96 +/- 11 ms), and age-matched control subjects (EF 64 +/- 5%, QRS 87 +/- 9 ms). Mean DI was significantly different between the 3 groups (HF-wide QRS: 152 +/- 44 ms, HF-narrow QRS: 121 +/- 58 ms, and control subjects: 65 +/- 12 ms; p < 0.0001) and greater in the HF-wide QRS (p < 0.0001) and HF-narrow QRS (p = 0.005) groups compared with control subjects. We found that DI had a good correlation with 2-dimensional (r = 0.65, p = 0.012) and 3-dimensional (r = 0.68, p = 0.008) echocardiographic dyssynchrony. CONCLUSIONS Quantitative assessment of global CT-derived DI, based on changes in wall thickness over time, is highly reproducible and renders significant differences between subjects most likely to have dyssynchrony and age-matched control subjects. (J Am Coll Cardiol Img 2008; 1:772-81) (C) 2008 by the American College of Cardiology Foundation C1 [Truong, Quynh A.; Sarwar, Ammar; Nasir, Khurram; Brady, Thomas J.; Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Singh, Jagmeet P.; Handschumacher, Mark] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02114 USA. [Auricchio, Angelo; Faletra, Francesco F.; Sorgente, Antonio; Conca, Cristina; Moccetti, Tiziano] Cardioctr Ticino, Lugano, Switzerland. RP Truong, QA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU NIH [T32HL076136] FX Drs. Truong and Nasir received support from NIH grant T32HL076136. Dr. Auricchio is a consultant for GE Healthcare. NR 32 TC 25 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD NOV PY 2008 VL 1 IS 6 BP 772 EP 781 DI 10.1016/j.jcmg.2008.07.014 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V13EM UT WOS:000207650100011 PM 19212461 ER PT J AU Lehman, SJ Schlett, CL Bamberg, F Nieman, K Abbara, S Hoffmann, U AF Lehman, Sam J. Schlett, Christopher L. Bamberg, Fabian Nieman, Koen Abbara, Suhny Hoffmann, Udo TI Appearance of Acute and Chronic Coronary Occlusions in Contrast-Enhanced Cardiac Computed Tomography SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material C1 [Lehman, Sam J.; Schlett, Christopher L.; Bamberg, Fabian; Nieman, Koen; Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Bamberg, Fabian; Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hoffmann, U (reprint author), 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 0 TC 3 Z9 3 U1 1 U2 1 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 NOV PY 2008 VL 1 IS 6 BP 809 EP 811 DI 10.1016/j.jcmg.2008.07.016 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V13EM UT WOS:000207650100015 PM 19356518 ER PT J AU Adler, LA Spencer, TJ Williams, DW Moore, RJ Michelson, D AF Adler, Lenard A. Spencer, Thomas J. Williams, David W. Moore, Rodney J. Michelson, David TI Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults With ADHD Final Report of a 4-Year Study SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE atomoxetine; attention deficit/hyperactivity disorder; adult; long-term treatment AB Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial since the interim report), receiving up to 221 weeks of treatment. Primary efficacy measure was the Conners'Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv: SV) Total ADHD Symptom score. Adverse events and vital signs were assessed. Results: CAARS-Inv: SV Total ADHD Symptom scores decreased 30.2% (p < .001) during treatment. Similar, significant decreases were noted for the secondary efficacy measures, including the Sheehan Disability Scale Total score, which improved 25.3% (p < .001). Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects. Conclusions: Results of this open-label study support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD. (J. of Att. Dis. 2008; 12(3) 248-253) C1 [Adler, Lenard A.] NYU, Sch Med, New York, NY 10016 USA. [Adler, Lenard A.] New York VA Harbor Healthcare Syst, New York, NY USA. [Spencer, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adler, LA (reprint author), NYU, Sch Med, 530 1st Ave,Suite 7D, New York, NY 10016 USA. EM lenard.adler@med.nyu.edu OI Adler, Len/0000-0002-9812-8234 FU Eli Lilly and Company FX Research funded by Eli Lilly and Company. Correspondence concerning this article should be addressed to Lenard A. Adler, MD, New York University School of Medicine, 530 1st Avenue, Suite 7D, New York, NY 10016; e-mail: lenard. adler@med.nyu.edu. NR 19 TC 50 Z9 51 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD NOV PY 2008 VL 12 IS 3 BP 248 EP 253 DI 10.1177/1087054708316250 PG 6 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GU UT WOS:000207520900007 PM 18448861 ER PT J AU Ding, YP Onodera, Y Lee, JC Hooper, DC AF Ding, Yanpeng Onodera, Yoshikuni Lee, Jean C. Hooper, David C. TI NorB, an Efflux Pump in Staphylococcus aureus Strain MW2, Contributes to Bacterial Fitness in Abscesses SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MEDIATED RESISTANCE; EXPRESSION; MODEL; MGRA; PROTEIN; GENES; FLUOROQUINOLONES; INFECTIONS; REGULATOR; SEQUENCES AB While remaining a major problem in hospitals, Staphylococcus aureus is now spreading in communities. Strain MW2 (USA400 lineage) and other community methicillin-resistant S. aureus strains most commonly cause skin infections with abscess formation. Multidrug resistance (MDR) efflux pumps contribute to antimicrobial resistance but may also contribute to bacterial survival by removal of environmental toxins. In S. aureus, NorA, NorB, NorC, and Tet38 are chromosomally encoded efflux pumps whose overexpression can confer MDR to quinolones and other compounds (Nor pumps) or tetracyclines alone (Tet38), but the natural substrates of these pumps are not known. To determine the role of these efflux pumps in a natural environment in the absence of antibiotics, we used strain MW2 in a mouse subcutaneous abscess model and compared pump gene expression as determined by reverse transcription-PCR in the abscesses and in vitro. norB and tet38 were selectively upregulated in vivo more than 171- and 24-fold, respectively, whereas norA and norC were down-regulated. These changes were associated with an increase in expression of mgrA, which encodes a transcriptional regulator known to affect pump gene expression. In competition experiments using equal inocula of a norB or tet38 mutant and parent strain MW2, each mutant exhibited growth defects of about two- to threefold in vivo. In complementation experiments, a single-copy insertion of norB (but not a single-copy insertion of tet38) in the attB site within geh restored the growth fitness of the norB mutant in vivo. Our findings indicate that some MDR pumps, like NorB, can facilitate bacterial survival when they are overexpressed in a staphylococcal abscess and may contribute to the relative resistance of abscesses to antimicrobial therapy, thus linking bacterial fitness and resistance in vivo. C1 [Ding, Yanpeng; Onodera, Yoshikuni; Hooper, David C.] Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Jean C.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU National Institutes of Health [AI093288] FX This work was supported in part by Public Health Service grant AI093288 from the National Institutes of Health (to D. C. H).; We thank Chia Y. Lee for providing plasmid pYL112 Delta 19 and technical assistance. NR 31 TC 55 Z9 59 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2008 VL 190 IS 21 BP 7123 EP 7129 DI 10.1128/JB.00655-08 PG 7 WC Microbiology SC Microbiology GA 361ZF UT WOS:000260166900021 PM 18723624 ER PT J AU Truong-Bolduc, QC Ding, YP Hooper, DC AF Truong-Bolduc, Que Chi Ding, Yanpeng Hooper, David C. TI Posttranslational Modification Influences the Effects of MgrA on norA Expression in Staphylococcus aureus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE TRANSPORTER; SIGMA(B) REGULON; SIGB OPERON; REGULATOR; AUTOLYSIS; TRANSCRIPTION; SHOCK; GENE; RSBU; SAR AB MgrA is a global regulator in Staphylococcus aureus. Differences in the effects of MgrA on norA expression have been reported for different strains, which varied in rsbU, a gene that affects the expression of sigB, which encodes an alternative sigma factor involved in stress responses. We hypothesized that MgrA was modified by sigB-dependent factors that affected its ability to control the expression of the norA efflux pump. Heterologously expressed MgrA purified from Escherichia coli was incubated with crude extracts (CE) from strains RN6390 (rsbU) and SH1000 (rsbU(+)) and tested for binding to the norA promoter. Purified MgrA exhibited greater binding to norA promoter DNA after being incubated with SH1000 CE than MgrA incubated with the RN6390 CE. Phosphorylation of MgrA occurring in cell extracts caused it to lose the ability to bind norA promoter DNA. Overexpression of pknB, encoding a candidate serine/threonine kinase, produced increased phospho-MgrA and led to a fivefold increase in the transcript level of norA for both RN6390 and SH1000, as well as a fourfold increase in the MICs of norfloxacin and ciprofloxacin for these two strains. The levels of expression of pknB in RN6390 and SH1000, however, indicated that additional factors related to rsbU or sigB contribute to the differential regulatory effects of MgrA on norA expression. C1 [Truong-Bolduc, Que Chi; Ding, Yanpeng; Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis & Med Serv, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU U.S. Public Health Service [R37 AI023988]; National Institutes of Health FX This work was supported in part by grant R37 AI023988 from the U.S. Public Health Service, National Institutes of Health (to D.C.H.). NR 29 TC 42 Z9 43 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2008 VL 190 IS 22 BP 7375 EP 7381 DI 10.1128/JB.01068-08 PG 7 WC Microbiology SC Microbiology GA 365TC UT WOS:000260429700007 PM 18805983 ER PT J AU Ruddock, MW Stein, A Landaker, E Park, J Cooksey, RC McClain, D Patti, ME AF Ruddock, Mark W. Stein, Andrew Landaker, Edwin Park, Jun Cooksey, Robert C. McClain, Donald Patti, Mary-Elizabeth TI Saturated Fatty Acids Inhibit Hepatic Insulin Action by Modulating Insulin Receptor Expression and Post-receptor Signalling SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE beta-oxidation; insulin signalling; insulin resistance; liver; palmitate ID PROTEIN-KINASE-C; PROLIFERATOR-ACTIVATED RECEPTORS; SKELETAL-MUSCLE; PERIPHERAL INSULIN; GLUCOSE-PRODUCTION; DIABETES MELLITUS; GENE-EXPRESSION; IGF-1 RECEPTORS; RESISTANCE; HEPATOCYTES AB Free fatty acids (FFAs) are proposed to play a pathogenic role in both peripheral and hepatic insulin resistance. We have examined the effect of saturated FFA on insulin signalling (100 nM) in two hepatocyte cell lines. Fao hepatoma cells were treated with physiological concentrations of sodium palmitate (0.25 mM) (16:0) for 0.25-48 h. Palmitate decreased insulin receptor (IR) protein and mRNA expression in a dose- and time-dependent manner (35% decrease at 12 h). Palmitate also reduced insulin-stimulated IR and IRS-2 tyrosine phosphorylation, IRS-2-associated PI 3-kinase activity, and phosphorylation of Akt, p70 S6 kinase, GSK-3 and FOXO1A. Palmitate also inhibited insulin action in hepatocytes derived from wild-type IR (+/+) mice, but was ineffective in IR-deficient (-/-) cells. The effects of palmitate were reversed by triacsin C, an inhibitor of fatty acyl CoA synthases, indicating that palmitoyl CoA ester formation is critical. Neither the non-metabolized bromopalmitate alone nor the medium chain fatty acid octanoate (8:0) produced similar effects. However, the CPT-1 inhibitor (+/-)-etomoxir and bromopalmitate (in molar excess) reversed the effects of palmitate. Thus, the inhibition of insulin signalling by palmitate in hepatoma cells is dependent upon oxidation of fatty acyl-CoA species and requires intact insulin receptor expression. C1 [Ruddock, Mark W.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Ruddock, MW (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.ruddock@randox.com FU National Institutes of Health [DK02526, DK62948]; Markey Charitable Trust; Joslin Diabetes Center FX National Institutes of Health (DK02526 and DK62948); the Markey Charitable Trust, and Joslin Diabetes Center. NR 49 TC 43 Z9 49 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0021-924X J9 J BIOCHEM JI J. Biochem. PD NOV PY 2008 VL 144 IS 5 BP 599 EP 607 DI 10.1093/jb/mvn105 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 367NQ UT WOS:000260559100006 PM 18713797 ER PT J AU Gaige, TA Kwon, HS Dai, GP Cabral, VC Wang, RP Nam, YS Engelward, BP Wedeen, VJ So, PTC Gilbert, RJ AF Gaige, Terry A. Kwon, Hyuk Sang Dai, Guangping Cabral, Victor C. Wang, Ruopeng Nam, Yoon Sung Engelward, Bevin P. Wedeen, Van J. So, Peter T. C. Gilbert, Richard J. TI Multiscale structural analysis of mouse lingual myoarchitecture employing diffusion spectrum magnetic resonance imaging and multiphoton microscopy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE multiscale imaging; biomedical optics; multiphoton microscopy; diffusion weighted magnetic resonance imaging; second-harmonic generation; tissue morphology ID 3-DIMENSIONAL MYOARCHITECTURE; BOVINE TONGUE; 2ND-HARMONIC GENERATION; 2-PHOTON MICROSCOPY; FIBER ARCHITECTURE; IN-VIVO; TRACTOGRAPHY; DEFORMATION; MECHANICS; MYOCYTES AB The tongue consists of a complex, multiscale array of myofibers that comprise the anatomical underpinning of lingual mechanical function. 3-D myoarchitecture was imaged in mouse tongues with diffusion spectrum magnetic resonance imaging (DSI) at 9.4 T (b(max) 7000 s/mm, 150-mu m isotropic voxels), a method that derives the preferential diffusion of water/voxel, and high-throughput (10 fps) two-photon microscope (TPM). Net fiber alignment was represented for each method in terms of the local maxima of an orientational distribution function (ODF) derived from the local diffusion (DSI) and 3-D structural autocorrelation (TPM), respectively. Mesoscale myofiber tracts were generated by alignment of the principal orientation vectors of the ODFs. These data revealed a consistent relationship between the properties of the respective ODFs and the virtual superimposition of the distributed mesoscale myofiber tracts. The identification of a mesoscale anatomical construct, which specifically links the microscopic and macroscopic spatial scales, provides a method for relating the orientation and distribution of cells and subcellular components with overall tissue morphology, thus contributing to the development of multiscale methods for mechanical analysis. (C) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3046724] C1 MIT, Dept Mech & Biol Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rgilbert@mit.edu RI Nam, Yoon Sung/G-2713-2011 OI Nam, Yoon Sung/0000-0002-7302-6928 NR 30 TC 6 Z9 7 U1 0 U2 2 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2008 VL 13 IS 6 AR 064005 DI 10.1117/1.3046724 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 403RY UT WOS:000263100900011 PM 19123652 ER PT J AU Lee, S Vu, DH Hinds, MF Davis, SJ Liang, A Hasan, T AF Lee, Seonkyung Vu, Danthu H. Hinds, Michael F. Davis, Steven J. Liang, Alvin Hasan, Tayyaba TI Pulsed diode laser-based singlet oxygen monitor for photodynamic therapy: in vivo studies of tumor-laden rats SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE photodynamic therapy; singlet oxygen; light dosimetry ID BASAL-CELL CARCINOMAS; PROSTATE-CANCER; DOSIMETRY; ACID; INACTIVATION; GROWTH AB Photodynamic therapy (PDT) is a promising cancer treatment that involves optical excitation of photosensitizers that promote oxygen molecules to the metastable O-2(a(1)Delta) state (singlet oxygen). This species is believed to be responsible for the destruction of cancerous cells during PDT. We describe a fiber optic-coupled, pulsed diode laser-based diagnostic for singlet oxygen. We use both temporal and spectral filtering to enhance the detection of the weak O-2(a -> X) emission near 1.27 mu m. We present data that demonstrate real-time singlet oxygen production in tumor-laden rats with chlorin e6 and 5-aminolevulinic acid-induced protoporphyrin photosensitizers. We also observe a positive correlation between post-PDT treatment regression of the tumors and the relative amount of singlet oxygen measured. These results are promising for the development of the sensor as a real-time dosimeter for PDT. (c) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3042265] C1 [Lee, Seonkyung; Vu, Danthu H.; Hinds, Michael F.; Davis, Steven J.] Phys Sci Inc, Andover, MA 01810 USA. [Liang, Alvin; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Lee, S (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM lee@psicorp.com FU NCI NIH HHS [5 R44 CA096243-03, R44 CA096243, R44 CA096243-03] NR 24 TC 21 Z9 21 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2008 VL 13 IS 6 AR 064035 DI 10.1117/1.3042265 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 403RY UT WOS:000263100900040 PM 19123681 ER PT J AU Mcgee, S Mirkovic, J Mardirossian, V Elackattu, A Yu, CC Kabani, S Gallagher, G Pistey, R Galindo, L Badizadegan, K Wang, Z Dasari, R Feld, MS Grillone, G AF McGee, Sasha Mirkovic, Jelena Mardirossian, Vartan Elackattu, Alphi Yu, Chung-Chieh Kabani, Sadru Gallagher, George Pistey, Robert Galindo, Luis Badizadegan, Kamran Wang, Zimmern Dasari, Ramachandra Feld, Michael S. Grillone, Gregory TI Model-based spectroscopic analysis of the oral cavity: impact of anatomy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE spectroscopy; reflectance; fluorescence ID DIFFUSE-REFLECTANCE SPECTROSCOPY; ARTIFICIAL NEURAL-NETWORK; FLUORESCENCE SPECTROSCOPY; IN-VIVO; AUTOFLUORESCENCE SPECTROSCOPY; LIGHT-SCATTERING; TURBID MEDIA; TISSUE; CLASSIFICATION; DIAGNOSIS AB In order to evaluate the impact of anatomy on the spectral properties of oral tissue, we used reflectance and fluorescence spectroscopy to characterize nine different anatomic sites. All spectra were collected in vivo from healthy oral mucosa. We analyzed 710 spectra collected from the oral cavity of 79 healthy volunteers. From the spectra, we extracted spectral parameters related to the morphological and biochemical properties of the tissue. The parameter distributions for the nine sites were compared, and we also related the parameters to the physical properties of the tissue site. k-Means cluster analysis was performed to identify sites or groups of sites that showed similar or distinct spectral properties. For the majority of the spectral parameters, certain sites or groups of sites exhibited distinct parameter distributions. Sites that are normally keratinized, most notably the hard palate and gingiva, were distinct from nonkeratinized sites for a number of parameters and frequently clustered together. The considerable degree of spectral contrast (differences in the spectral properties) between anatomic sites was also demonstrated by successfully discriminating between several pairs of sites using only two spectral parameters. We tested whether the 95% confidence interval for the distribution for each parameter, extracted from a subset of the tissue data could correctly characterize a second set of validation data. Excellent classification accuracy was demonstrated. Our results reveal that intrinsic differences in the anatomy of the oral cavity produce significant spectral contrasts between various sites, as reflected in the extracted spectral parameters. This work provides an important foundation for guiding the development of spectroscopic-based diagnostic algorithms for oral cancer. c 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.2992139] C1 [McGee, Sasha; Mirkovic, Jelena; Yu, Chung-Chieh; Galindo, Luis; Dasari, Ramachandra; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Mardirossian, Vartan; Elackattu, Alphi; Pistey, Robert; Wang, Zimmern; Grillone, Gregory] Boston Med Ctr, Boston, MA 02118 USA. [Kabani, Sadru; Gallagher, George] Boston Univ, Sch Dent Med, Dept Oral & Maxillofacial Pathol, Boston, MA 02118 USA. [Badizadegan, Kamran] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mcgee, S (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave,Bldg 6-218M, Cambridge, MA 02139 USA. EM samcgee@mit.edu RI Mirkovic, Jelena/A-6253-2013 FU NCI NIH HHS [R01 CA097966, R01 CA097966-03]; NCRR NIH HHS [P41 RR002594, P41 RR002594-21, P41 RR02594-21] NR 39 TC 25 Z9 25 U1 0 U2 5 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2008 VL 13 IS 6 AR 064034 DI 10.1117/1.2992139 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 403RY UT WOS:000263100900039 PM 19123680 ER PT J AU Stoothoff, WH Bacskai, BJ Hyman, BT AF Stoothoff, William H. Bacskai, Brian J. Hyman, Bradley T. TI Monitoring tau-tubulin interactions utilizing second harmonic generation in living neurons SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE second harmonic generation; microtubule; Alzheimer's disease; tau protein; neuron; axon ID PROGRESSIVE SUPRANUCLEAR PALSY; INHERITED DEMENTIA FTDP-17; EXON 10; ALZHEIMERS-DISEASE; PROTEIN-TAU; DIFFERENTIAL EXPRESSION; PICKS-DISEASE; IN-VITRO; MICROTUBULES; BINDING AB Tau is a microtubule associated protein that is localized to the axon in neurons. During pathological conditions, including frontotemporal dementia (FTD), a shift in tau isoforms occurs that leads to enhanced expression of a form of tau with four (rather than three) microtubule binding repeats; this has been postulated to alter microtubule structure. Second harmonic generation (SHG) is a technique that allows the visualization of intact microtubules in axons of living neurons without the need for labeling or fixing. We examined how the presence of exogenous tau influences SHG in living neurons. Our results show that the presence of tau significantly enhances SHG, specifically in neuronal axons, despite the presence of tau throughout the entire cell. Our data also suggest that the presence or absence of the fourth microtubule binding repeat does not significantly alter tau's ability to enhance SHG. These results provide evidence that SHG is a useful, noninvasive tool to study tau-microtubule interactions in axons; further, it appears that tau overexpression, rather than specific isoforms, is the major contributor to tau-induced changes in axonal microtubule SHG signal. (c) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3050422] C1 [Stoothoff, William H.; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org FU NIA NIH HHS [AG 026249, P50 AG 05134, P50 AG005134, R01 AG026249, R01 AG026249-05]; NIBIB NIH HHS [EB000768, R01 EB000768] NR 40 TC 11 Z9 11 U1 1 U2 9 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2008 VL 13 IS 6 AR 064039 DI 10.1117/1.3050422 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 403RY UT WOS:000263100900044 PM 19123685 ER PT J AU Okike, K Kocher, MS Mehlman, CT Heckman, JD Bhandari, M AF Okike, Kanu Kocher, Mininder S. Mehlman, Charles T. Heckman, James D. Bhandari, Mohit TI Nonscientific Factors Associated with Acceptance for Publication in The Journal of Bone and Joint Surgery (American Volume) SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BIAS; OUTCOMES AB Background: While it is widely accepted that scientific factors may render a study more likely to be accepted for publication, it is less clear whether nonscientific factors may also be associated with publication. The purpose of this study was to identify the nonscientific factors associated with acceptance for publication by The Journal of Bone and Joint Surgery (American Volume). Methods: A total of 1173 manuscripts submitted to The Journal of Bone and Joint Surgery between January 1, 2004, and June 30, 2005, for publication as scientific articles were analyzed as part of a study on publication bias in the editorial decision-making process. Information was collected on nonscientific factors plausibly associated with acceptance for publication, including study location, conflict-of-interest disclosure, sex of the author, primary language, and the number of prior publications by the corresponding author in frequently cited orthopaedic journals. The final disposition term (acceptance or rejection) was recorded, and logistic regression was used to identify factors associated with acceptance for publication. Results: Manuscripts from countries other than the United States or Canada were significantly less likely to be accepted (odds ratio, 0.51; 95% confidence interval, 0.28 to 0.92; p = 0.026). Factors positively associated with acceptance for publication were conflict-of-interest disclosure involving a nonprofit entity (odds ratio, 1.92; 95% confidence interval, 1.35 to 2.73; p < 0.001) and ten or more prior publications in frequently cited orthopaedic journals by the corresponding author (odds ratio, 2.01; 95% confidence interval, 1.33 to 3.05; p = 0.001). We did not find a significant association between acceptance and conflict-of-interest disclosure involving a for-profit company, sex of the corresponding author, or primary language. Conclusions: Manuscripts submitted to The Journal of Bone and Joint Surgery were more likely to be accepted if they were from the United States or Canada, reported a conflict of interest related to a nonprofit entity, or were authored by an individual with ten or more prior publications in frequently cited orthopaedic journals. C1 [Kocher, Mininder S.] Harvard Univ, Childrens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Mehlman, Charles T.] Univ Cincinnati, Cincinnati Childrens Hosp, Coll Med, Med Ctr,Div Pediat Orthopaed Surg, Cincinnati, OH 45229 USA. [Bhandari, Mohit] McMaster Univ, Hamilton Gen Hosp, Dept Orthopaed Surg, Hamilton, ON L8L 2X2, Canada. RP Okike, K (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM okike@post.harvard.edu OI Okike, Kanu/0000-0001-9310-9969 FU Department of Orthopaedic Surgery; National Institutes of Health; Canadian Institutes of Health Research; U.S. Department of Defense; Orthopaedic Trauma Association; Stryker; Smith and Nephew FX In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants of less than $10,000 from the Department of Orthopaedic Surgery at Children's Hospital Boston. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from a commercial entity (The Journal of Bone and Joint Surgery). One author received research funding in excess of $10,000 from the National Institutes of Health, the Canadian Institutes of Health Research, the U.S. Department of Defense, the Orthopaedic Trauma Association, Stryker, and Smith and Nephew. Also, a commercial entity (DePuy Spine) paid or directed in any one year, or agreed to pay or direct, benefits in excess of $10,000 to a research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which one or more of the authors, or a member of his or her immediate family, is affiliated or associated. NR 9 TC 21 Z9 21 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2008 VL 90A IS 11 BP 2432 EP 2437 DI 10.2106/JBJS.G.01687 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 372NA UT WOS:000260907100014 PM 18978412 ER PT J AU Pham, TN Klein, MB Gibran, NS Arnoldo, BD Gamelli, RL Silver, GM Jeschke, MG Finnerty, CC Tompkins, RG Herndon, DN AF Pham, Tam N. Klein, Matthew B. Gibran, Nicole S. Arnoldo, Brett D. Gamelli, Richard L. Silver, Geoffrey M. Jeschke, Marc G. Finnerty, Celeste C. Tompkins, Ronald G. Herndon, David N. TI Impact of Oxandrolone Treatment on Acute Outcomes After Severe Burn Injury SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID ALCOHOLIC HEPATITIS; HOST RESPONSE; CHILDREN; PHASE; INFLAMMATION; MULTICENTER; RECOVERY; INSULIN; WEIGHT; TRIAL AB Pharmacologic modulation of hypermetabolism clearly benefits children with major burns, however, its role in adult burns remains to be defined. Oxandrolone appears to be a promising anabolic agent although few outcome data are as yet available. We examined whether early oxandrolone treatment in severely burned adults was associated with improved outcomes during acute hospitalization. We evaluated for potential associations between oxandrolone treatment and outcomes in a large cohort of severely burned adults in the context of a multicenter observational study. Patients were dichotomized with respect to oxandrolone treatment, defined as administration within 7 days after admission, with duration of at least 7 days. Acute hospitalization outcomes were compared with univariate and multivariate analyses. One hundred seventeen patients were included in this analysis. Mean patient age was 42.6 years (range, 18-86); 77% were male, with an average TBSA of 44.1%. Baseline and injury characteristics were similar among treatment and nontreatment cohorts. Oxandrolone treatment (N = 59) did not impact length of stay but was associated with a lower mortality rate (P = .01) by univariate analysis. Oxandrolone treatment was independently associated with higher survival by adjusted analyses (P = .02). Examination of early oxandrolone treatment in this cohort of severely burned adults suggests that this therapy is safe and may be associated with improved survival. Further studies are necessary to define the exact mechanisms by which oxandrolone is beneficial during inpatient treatment. (J Burn Care Res 2008;29:902-906) C1 [Pham, Tam N.; Klein, Matthew B.; Gibran, Nicole S.] Univ Washington, Harborview Med Ctr, Burn Ctr, Seattle, WA 98104 USA. [Arnoldo, Brett D.] Univ Texas SW, Parkland Mem Hosp, Dept Surg, Dallas, TX USA. [Gamelli, Richard L.; Silver, Geoffrey M.] Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. [Jeschke, Marc G.; Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX USA. [Jeschke, Marc G.; Finnerty, Celeste C.; Herndon, David N.] Shriners Hosp Crippled Children, Galveston, TX USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Pham, TN (reprint author), Univ Washington, Harborview Med Ctr, Burn Ctr, Box 359796,325 9th Ave, Seattle, WA 98104 USA. FU National Institute of General Medical Sciences FX The Inflammation and the Host Response to Injury "Glue Grant' program is supported by the National Institute of General Medical Sciences. NR 23 TC 10 Z9 10 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2008 VL 29 IS 6 BP 902 EP 906 DI 10.1097/BCR.0b013e31818ba14d PG 5 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 372ZD UT WOS:000260939900010 PM 18849836 ER PT J AU Boisot, S Beede, J Isakson, S Chiu, A Clopton, P Januzzi, J Maisel, AS Fitzgerald, RL AF Boisot, Saskia Beede, Jennifer Isakson, Susan Chiu, Albert Clopton, Paul Januzzi, James Maisel, Alan S. Fitzgerald, Robert L. TI Serial Sampling of ST2 Predicts 90-Day Mortality Following Destabilized Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE ST2; B-type natriuretic peptide; Pro-B-type natriuretic peptide; heart failure ID RECEPTOR FAMILY-MEMBER; MYOCARDIAL-INFARCTION; PROMOTER USAGE; IL-1 RECEPTOR; EXPRESSION; GENE; CYTOKINES; BNP AB Background: To prospectively determine the prognostic utility of serial sampling of the interleukin-1 receptor family member. ST2, for predicting 90-day mortality in patients with heart failure (HF) admitted to a Veteran Affairs Medical Center. Methods and Results: A total 150 patients hospitalized with acutely destabilized HE were followed at the Veteran Affairs Healthcare System in San Diego, CA. Multiple cardiac-related parameters were measured including ST2. B-type natriuretic peptide (BNP), NT-proBNP, and blood urea nitrogen (BUN). Plasma samples were collected ill 6 time points between admission and discharge. Biomarker concentrations were correlated to survival at 90 days. Uni- and multivariate analyses Were used to identify prognostic variables. Front admission to discharge, percent change in ST2 was strongly predictive of 90-day mortality: those patients whose ST2 values decreased by 15.5% or more during the study period had a 7% chance of death. whereas patients whose ST2 levels failed to decrease by 15.5% ill this time interval had a 33% chance of dying. Conclusions: Percent change in ST2 concentrations during acute HF treatment is predictive of 90-day mortality and wits independent of BNP or NT-proBNP levels. ST2 may provide clinicians with an additional 1001 for guiding treatment in patients With acute destabilized HE (J Cardiac Fail 2008:14:732-738) C1 [Boisot, Saskia; Beede, Jennifer; Isakson, Susan; Chiu, Albert; Clopton, Paul; Maisel, Alan S.; Fitzgerald, Robert L.] Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA. [Boisot, Saskia; Fitzgerald, Robert L.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Januzzi, James] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Boisot, S (reprint author), VASDHS Chem, 113-3350 La Jolla Village Dr, San Diego, CA 92161 USA. NR 27 TC 77 Z9 85 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD NOV PY 2008 VL 14 IS 9 BP 732 EP 738 DI 10.1016/j.cardfail.2008.06.415 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 377SB UT WOS:000261269800004 PM 18995177 ER PT J AU Goldman, S McCarren, M Morkin, E Ladenson, P Edson, R Warren, S Ohm, J Thai, H Churby, L Barnhill, J O'Brien, T Anand, I Warner, A Dunlap, M Hattle, B Erikson, J Shih, MC Lavori, P AF Goldman, Steven McCarren, Madeline Morkin, Eugene Ladenson, Paul Edson, Robert Warren, Stuart Ohm, Janet Thai, Hoang Churby, Lori Barnhill, Jamie O'Brien, Terrence Anand, Inder Warner, Alberta Dunlap, Mark Hattle, Brack Erikson, John Shih, Mei-Chung Lavori, Phil TI DITPA, a Thyroid Hormone Analog to Treat Heart Failure: Phase II Trial VA Cooperative Study SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 12th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 21-24, 2008 CL Toronto, CANADA SP Heart Failure Soc Amer C1 [Goldman, Steven; Ohm, Janet; Thai, Hoang] So Arizona VA Hlth Care Syst, Tucson, AZ USA. [McCarren, Madeline] VA Ctr Medicat Safety, Hines, IL USA. [Morkin, Eugene] Univ Arizona Hlth Sci, Tucson, AZ USA. [Ladenson, Paul] Johns Hopkins Univ, Baltimore, MD USA. [Edson, Robert; Shih, Mei-Chung; Lavori, Phil] Palo Alto CSP Coordinating Ctr, Palo Alto, CA USA. [Warren, Stuart; Barnhill, Jamie] CSP Clin Res Pharm Coordinat Ctr, Albuquerque, NM USA. [O'Brien, Terrence] VA Med Ctr, Charleston, SC USA. [Anand, Inder] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Warner, Alberta] Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dunlap, Mark] Louis Stokes VA Healthcare Syst, Cleveland, OH USA. [Hattle, Brack] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Erikson, John] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD NOV PY 2008 VL 14 IS 9 BP 796 EP 796 DI 10.1016/j.cardfail.2008.10.008 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 377SB UT WOS:000261269800013 ER PT J AU Harissi-Dagher, M Todani, A Melki, SA AF Harissi-Dagher, Mona Todani, Arnit Melki, Samir A. TI Laser in situ keratomileusis buttonhole: Classification and management algorithm SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT 108th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 23-26, 2004 CL New Orleans, LA SP Amer Acad Ophthalmol ID MITOMYCIN-C; PHOTOREFRACTIVE KERATECTOMY; EPITHELIAL INGROWTH; LASIK FLAP; COMPLICATIONS; ETIOLOGY; SURGERY; MYOPIA AB PURPOSE: To report the classification, management, and visual outcomes after laser in situ keratomileusis (LASIK) flap buttonhole caused by a microkeratome cut. SETTING: Private practice, Boston, Massachusefts, USA. METHODS: This retrospective observational case series comprised 15 patients with an intraoperative LASIK flap buttonhole or near buttonhole. In all cases, the flap was left in place or repositioned without excimer laser treatment. Buttonholes were classified by stage, and a treatment algorithm based on the stage was devised to determine the timing and type of intervention. The uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), and complications associated with the laser vision correction surgery were reported. RESULTS: Postoperative follow-up ranged from 1 week to 23 months. All 9 patients who were retreated had a postoperative UCVA of 20/25 or better. No retreated patient lost BSCVA. Before retreatment, the median UCVA was 20/80 (range 20/40(-1) to counting fingers), the median BSCVA was 20/20(-2) (range 20/15(-1) to 20/70), and the spherical equivalent (SE) refractive errors ranged from -1.00 to -6.62 diopters (D). After retreatment, the median UCVA was 20/20(-2) (range 20/15(-1) to 20/25(-1)), the median BSCVA was 20/20 (range 20/15 to 20/20(-3)), and the SE refractive errors ranged from +0.50 to -0.75 D. Complications after laser correction treatment included overcorrection in 3 patients and corneal haze in 2 patients. CONCLUSIONS: Classification of buttonholes was helpful in guiding treatment. Good UCVA and BSCVA were achieved by following a simple treatment algorithm based on surface ablation. C1 [Melki, Samir A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. [Harissi-Dagher, Mona] Univ Montreal, Montreal, PQ, Canada. RP Melki, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu NR 24 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD NOV PY 2008 VL 34 IS 11 BP 1892 EP 1899 DI 10.1016/j.jcrs.2008.08.013 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 375OI UT WOS:000261122800021 PM 19006735 ER PT J AU Zhao, R Daley, GQ AF Zhao, Rui Daley, George Q. TI From Fibroblasts to iPS Cells: Induced Pluripotency by Defined Factors SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE PLURIPOTENCY; REPROGRAMMING; EMBRYONIC STEM CELLS; iPS CELLS ID EMBRYONIC STEM-CELLS; REGULATES SELF-RENEWAL; HUMAN SOMATIC-CELLS; GENE-THERAPY; CANCER CELLS; C-MYC; MOUSE; DIFFERENTIATION; IMMORTALIZATION; GENERATION AB Patient-specific pluripotent cells may serve as a limitless source of transplantable tissue to treat a number of human blood and degenerative diseases without causing immune rejection. Recently, isolation of patient-specific induced pluripotent stem (iPS) cells was achieved by transducing fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc. However, the use of oncogenes and retrovirus in the current iPS cell establishment protocol raises safety concerns. To generate clinical quality iPS cells, the development of novel reprogramming methods that avoid permanent genetic modification is highly desired. The molecular mechanisms that mediate reprogramming are essentially unknown. We argue that establishment of a stable and self-sustainable ES-specific transcriptional regulatory network is essential for reprogramming. Such a system should include expression of Oct4, Sox2, Nanog and probably other pluripotenty-promoting factors from endogenous loci and establishment of a permissive epigenetic state to maintain such expression. In addition, though not yet proven experimentally, overcoming cellular senescence of fibroblasts by inactivating Rb and p53 pathways and up-regulating telomerase activity may also be required. J. Cell. Biochem. 105: 949-955, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Zhao, Rui; Daley, George Q.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA. [Zhao, Rui; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhao, Rui; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhao, Rui; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Zhao, Rui; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Karp 7214, Boston, MA 02215 USA. EM george.daley@childrens.harvard.edu FU Institutes of Health; NIH Director's Pioneer Award; Burroughs Wellcome Fund; Leukemia and Lymphoma Society; Harvard Stem Cell Institute; Children's Hospital Stem Cell Porgram; Howard Hughes Medical Institute FX Grant sponsors: Institutes of Health; NIH Director's Pioneer Award; Burroughs Wellcome Fund; Leukemia and Lymphoma Society; Harvard Stem Cell Institute; Children's Hospital Stem Cell Porgram; Howard Hughes Medical Institute. NR 54 TC 74 Z9 79 U1 3 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 2008 VL 105 IS 4 BP 949 EP 955 DI 10.1002/jcb.21871 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 374ZX UT WOS:000261083300003 PM 18668528 ER PT J AU Fragoza, K Alston, TA AF Fragoza, Keith Alston, Theodore A. TI Liquor made quicker: alcohol as a synthetic reagent for molecules in anesthesia SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Claude Bernard; Alfred Einhorn; Emil Fischer; Isabella Herb; Albert Hofmann; August Kekule; Charles Richet; Eduard Ritsert ID AGENTS AB Ethanol was an early anesthetic, and chemists transformed it into better ones. Hypnotic/anesthetic/analgesic molecules prepared from ethanol include barbiturates, benzocaine, chloral hydrate, chloroform, diethyl ether, ethyl chloride, ethylene, etomidate, meperidine, paraldehyde, phenacetin, procaine, tribromoethanol, and urethane. Ethanol was sometimes mixed deliberately with the other anesthetics, and John Snows inhaled amylene came from the fusel oil fraction of rotgut whisky. (C) 2008 Elsevier Inc. All rights reserved. C1 [Fragoza, Keith; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM talston@partners.org NR 43 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD NOV PY 2008 VL 20 IS 7 BP 556 EP 559 DI 10.1016/j.jclinane.2008.07.002 PG 4 WC Anesthesiology SC Anesthesiology GA 383XX UT WOS:000261708800015 PM 19019661 ER PT J AU Seminara, SB AF Seminara, Stephanie B. TI Lack of Association of Hypogonadotropic Genes with Age at Menarche: Prospects for the Future SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID HUMAN HEIGHT; VARIANTS; LOCI C1 Massachusetts Gen Hosp, Reprod Endocrinol Unit, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrinol Unit, Boston, MA 02114 USA. EM sseminara@partners.org NR 5 TC 2 Z9 2 U1 0 U2 0 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 NOV PY 2008 VL 93 IS 11 BP 4224 EP 4225 DI 10.1210/jc.2008-2010 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368ZI UT WOS:000260661900008 PM 18987281 ER PT J AU Wexler, DJ Nathan, DM Grant, RW Regan, S Van Leuvan, AL Cagliero, E AF Wexler, Deborah J. Nathan, David M. Grant, Richard W. Regan, Susan Van Leuvan, Allison L. Cagliero, Enrico TI Prevalence of Elevated Hemoglobin A1c among Patients Admitted to the Hospital without a Diagnosis of Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL PATIENTS; BLOOD-GLUCOSE CONTROL; US POPULATION; RISK-FACTORS; LIFE-STYLE; HYPERGLYCEMIA; MORTALITY; COMPLICATIONS; METFORMIN AB Context: One in four hospitalized patients has diagnosed diabetes. The prevalence of unrecognized, or undiagnosed, diabetes among hospitalized patients is not well established. Objective: Our objective was to determine the prevalence of unrecognized probable diabetes in this patient population determined by elevated hemoglobin A1c (HbA1c) level. Design: We conducted a prospective observational cohort trial with retrospective follow-up of patients with elevated HbA1c levels and no diagnosis of diabetes. HbA1c levels were obtained for all patients. Setting: The study was conducted at an acute care general hospital. Patients: Patients included 695 adult, nonobstetric patients admitted on 11 d in 2006. Main Outcome Measures: Outcome measures included rate of unrecognized probable diabetes, defined as admission HbA1c of more than 6.1% and no diagnosis of diabetes or treatment with antidiabetic medications before or during their admission and rate of unrecognized diabetes 1 yr after discharge. Results: Eighteen percent of hospitalized patients had elevated HbA1c levels without a diagnosis of diabetes. Random glucose levels poorly predicted elevated HbA1c levels (area under receiver operating characteristic curve, 0.60). Neither diagnosed diabetes nor HbA1c level was associated with length of stay or costs (P > 0.1 for all comparisons). Only 15% of patients with elevated HbA1c levels who continued to receive care within the system studied had diabetes diagnosed in the year after the index admission. Conclusions: Nearly one in five adult patients admitted to a large general hospital had unrecognized probable diabetes, based on elevated HbA1c levels. Random glucose levels during the hospital stay were poorly predictive of this condition. Few hospitalized patients with elevated HbA1c levels were diagnosed within the year after admission. (J Clin Endocrinol Metab 93: 4238-4244, 2008) C1 [Wexler, Deborah J.] Massachusetts Gen Hosp, Diabet Unit, Ctr Diabet, Boston, MA 02114 USA. [Grant, Richard W.; Regan, Susan] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, Diabet Unit, Ctr Diabet, Bulfinch 408,55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org OI Grant, Richard/0000-0002-6164-8025 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Career Development Award [K23 DK 080 228]; Earl Charlton Fund for Innovative Diabetes Research; NIDDK Career Development Award [K23 DK067452] FX D.J.W. is supported by a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Career Development Award (K23 DK 080 228). D.M.N. is supported in part by the Earl Charlton Fund for Innovative Diabetes Research. R. W. G. is supported by an NIDDK Career Development Award (K23 DK067452). NR 42 TC 33 Z9 34 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2008 VL 93 IS 11 BP 4238 EP 4244 DI 10.1210/jc.2008-1090 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368ZI UT WOS:000260661900012 PM 18697862 ER PT J AU Makimura, H Stanley, T Mun, D You, SM Grinspoon, S AF Makimura, Hideo Stanley, Takara Mun, David You, Sung Min Grinspoon, Steven TI The Effects of Central Adiposity on Growth Hormone (GH) Response to GH-Releasing Hormone-Arginine Stimulation Testing in Men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR RISK; ABDOMINAL OBESITY; FAT DISTRIBUTION; ENDOGENOUS GH; DEFICIENCY; INSULIN; SECRETION; WEIGHT AB Context: The relative contribution of central adiposity vs. weight on GH response to stimulation testing in obesity is not known. Objective: We aimed to assess the contribution of weight and specific measures of central and peripheral adiposity to GH response to GHRH-arginine testing in lean, overweight, and obese men. Design: A total of 75 men [mean age, 44.3 +/- 1.1 yr; body mass index (BMI), 28.8 +/- 0.7 kg/m(2)] were investigated. Subjects were classified as lean (BMI < 25 kg/m(2); n = 23), overweight (BMI >= 25 and <30 kg/m(2); n = 28), or obese (BMI >= 30 kg/m(2); n = 24). Subjects were also stratified by waist circumference (WC) (<102 cm, n = 47; >= 102 cm, n = 28). Body composition and regional adiposity were assessed by anthropometrics, dual-energy x-ray absorptiometry (DEXA), and abdominal computed tomography (CT) scans. Results: Peak stimulated GH was 36.4 +/- 5.4, 16.6 +/- 2.9, and 7.6 +/- 0.9 mu g/liter among lean, overweight, and obese subjects, respectively (P < 0.001 for all comparisons). Peak stimulated GH was 26.9 +/- 3.4 mu g/liter among subjects with WC less than 102 cm compared to 7.9 +/- 0.9 mu g/liter among subjects with WC of 102 cm or greater (P < 0.0001). Separate multivariate models using anthropometric, DEXA, and CT-derived measures of central adiposity demonstrated strong associations between peak stimulated GH and measures of central adiposity including WC, trunk fat by DEXA, and visceral adiposity by CT, controlling for age, BMI, and more general measures of adiposity. WC was independently associated with peak GH response to GHRH-arginine in a model including age, BMI, and hip circumference. In this model, BMI was no longer significant, and peak GH was reduced 1.02 mu g/liter for each 1 cm increase in WC (P = 0.02). Conclusions: GH response to GHRH-arginine testing is reduced in both overweight and obese subjects and negatively associated with indices of central abdominal obesity including WC, trunk fat, and visceral adipose tissue. The use of waist circumference, as a surrogate for central adiposity, adds predictive information to the determination of GH response, independent of BMI. (J Clin Endocrinol Metab 93: 4254-4260, 2008) C1 [Makimura, Hideo] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 211, Boston, MA 02114 USA. EM hmakimura@partners.org FU National Institutes of Health [HL085268-01A1]; National Center for Research Resources, National Institutes of Health [M01 RR-01066] FX This work was supported by National Institutes of Health Grant 1 R01 HL085268-01A1 (to S. G.). The studies were conducted at the General Clinical Research Center at the Massachusetts Institute of Technology and funded by a grant (M01 RR-01066) from the National Center for Research Resources, National Institutes of Health. NR 29 TC 55 Z9 56 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2008 VL 93 IS 11 BP 4254 EP 4260 DI 10.1210/jc.2008-1333 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368ZI UT WOS:000260661900014 PM 18765508 ER PT J AU Korzenik, JR AF Korzenik, Joshua R. TI Diverticulitis: New Frontiers for an Old Country Risk Factors and Pathogenesis SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 1st Meeting of the National-Diverticulitis-Study-Group CY DEC 02, 2005 CL New York, NY SP Natl Diverticulitis Study Grp DE diverticulitis; epidemilogy; intestinal microbiome ID NATURAL-HISTORY; DISEASE; COLON; DIET; FIBER; MEN AB The understanding of diverticulitis has advanced little beyond the initial postulates of Burkitt and Painter who proposed that diverticular disease results from a deficiency of dietary fiber. Diverticular disease and diverticulitis are viewed simply as a consequence of a diet which takes in relatively little fiber. Our understanding of diverticulitis has not advanced beyond these basic concepts. As many as two-thirds of individuals in the West have diverticular disease by the age of 85 years but only 10% to 25% will manifest any related clinical symptoms. Other than age several risk factors have been identified for the development of diverticular disease and diverticulitis. In particular obesity and red meat intake are risk factors. Smoking is more controversial and alcohol, coffee, and caffeine have not shown to be risk factors. Vegetable intake a strict vegetable diet and increased fiber intake decreases the risk of development of diverticular disease as well as diverticulitis. Physical activity also seems protective. Despite these evidence the risk factors and pathophysiology progression from asymptomatic diverticular disease to diverticulitis have been inadequately studies. This subject is reviewed in more detail in this manuscript. C1 Massachusetts Gen Hosp, Dept Internal Med, Crohns & Colitis Ctr, Dept Internal Med, Boston, MA 02114 USA. RP Korzenik, JR (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Crohns & Colitis Ctr, Dept Internal Med, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM jkorzenik@partners.org NR 15 TC 9 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2008 VL 42 IS 10 BP 1128 EP 1129 DI 10.1097/MCG.0b013e318188adb1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365IK UT WOS:000260399000016 PM 18936649 ER PT J AU Apostolou, I Verginis, P Kretschmer, K Polansky, J Huhn, J von Boehmer, H AF Apostolou, Irina Verginis, Panos Kretschmer, Karsten Polansky, Julia Huehn, Jochen von Boehmer, Harald TI Peripherally Induced Treg: Mode, Stability, and Role in Specific Tolerance SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Tregs; costimulation; immunosuppression ID REGULATORY T-CELLS; IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; THYMIC EPITHELIAL-CELLS; RETINOIC-ACID; IN-VIVO; GENE-EXPRESSION; REG-CELLS; ANTIGEN; DIFFERENTIATION AB Foxp3-expressing regulatory T cells (Treg) have an essential function of preventing autoimmune disease in man and mouse. Foxp3 binds to forkhead motifs of about 1,100 genes and the strength of binding increases upon phorbol 12-myristate 13-acetate/ionomycin stimulation. In Foxp3-expressing T cell hybridomas, Foxp3 promoter binding does not lead to activation or suppression of genes which becomes only visible after T cell activation. These findings are in line with observations by others that Foxp3 exerts important functions in collaboration with T cell receptor (TCR)-dependent transcription factors in a DNA-binding complex. Tregs can be generated when developing T cells encounter TCR agonist ligands in the thymus. This process apparently depends on costimulatory signals. In contrast. extrathymic conversion of naive T cells into Tregs appears to depend on transforming growth factor (TGF)-beta and is inhibited by costimulation. In fact, dendritic cell-derived retinoic acid helps the conversion process by counteracting the negative impact of costimulation. Tregs induced by subimmunogenic antigen delivery in vivo are much more stable than Tregs induced by antigenic stimulation in the presence of TGF-beta in vitro which correlates with the extent of demethylation of the Foxp3 locus. Tregs can be induced by conversion of antigen-specific T cells that occur with a very low frequency in wt mice. Conversion of naive cluster of differentiation (CD)4 T cells into Tregs by a single peptide of HY antigens results in complete antigen-specific tolerance to an entire set of HY epitopes recognized by CD4 as well as CD8 T cells when presented with male skin or hemopoietic grafts. C1 [Apostolou, Irina; Verginis, Panos; Kretschmer, Karsten; Polansky, Julia; Huehn, Jochen; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Harald_von_Boehmer@dfci.harvard.edu RI Kretschmer, Karsten/E-8174-2010; OI Polansky, Julia K./0000-0003-4727-2540 NR 39 TC 51 Z9 52 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2008 VL 28 IS 6 BP 619 EP 624 DI 10.1007/s10875-008-9254-8 PG 6 WC Immunology SC Immunology GA 399XW UT WOS:000262833600002 PM 18841451 ER PT J AU Smith, KA Griffin, JD AF Smith, Kendall A. Griffin, James D. TI Following the cytokine signaling pathway to leukemogenesis: a chronology SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID CELL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; DEPENDENT DNA POLYMERASE; PROTEIN-TYROSINE KINASES; MATERNAL MESSENGER-RNA; JAK-3 JANUS KINASE; TRANSCRIPTION FACTOR; INTERFERON-ALPHA; MYELOID-LEUKEMIA; ABELSON VIRUS AB Studies over the past 50 years revealing the molecular events that promote normal T lymphocyte cycle competence and progression led to a detailed understanding of how cytokines function to regulate normal hematopoietic cell proliferation. During that same period, the molecular and genetic changes introduced by the Philadelphia chromosome in chronic myelogenous leukemia were unraveled, and these have led to an understanding of how mutations that constitutively activate normal cytokine signaling pathways can cause unregulated cell proliferation and malignant transformation. Based on the paradigm established by these data, it is inescapable that going forward, investigators will operate under the hypothesis that transformation of additional cells and tissues will have a similar pathogenesis. C1 [Smith, Kendall A.] Cornell Univ, Div Immunol, Dept Med, Weill Med Coll, New York, NY 10065 USA. [Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Smith, KA (reprint author), Cornell Univ, Div Immunol, Dept Med, Weill Med Coll, 1300 York Ave, New York, NY 10065 USA. EM kasmith@med.cornell.edu NR 126 TC 4 Z9 4 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 NOV PY 2008 VL 118 IS 11 BP 3564 EP 3573 DI 10.1172/JCI35819 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 368LM UT WOS:000260622600009 PM 18982163 ER PT J AU Ausiello, DA AF Ausiello, Dennis A. TI Introduction of Samuel O. Thier, MD SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Ausiello, DA (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM dausiello@partners.org NR 1 TC 1 Z9 1 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 NOV PY 2008 VL 118 IS 11 BP 3805 EP 3810 DI 10.1172/JCI37666 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 368LM UT WOS:000260622600034 ER PT J AU Thier, SO AF Thier, Samuel O. TI Wandering SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thier, SO (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM sthier@partners.org 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 NOV PY 2008 VL 118 IS 11 BP 3810 EP 3811 DI 10.1172/JCI37560 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 368LM UT WOS:000260622600035 ER PT J AU Samii, A Carleton, BC Etminan, M AF Samii, Ali Carleton, Bruce C. Etminan, Mahyar TI Statin use and the risk of Parkinson disease: a nested case control study SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Coenzyme Q10; Inflammation; Neuroprotection; Parkinson disease; Statin ID CHOLESTEROL LEVELS; COENZYME Q(10) AB Using the British Columbia Linked Health Databases, we explored the association between the use of statin drugs and the risk of developind Parkinson disease (PD). We followed a cohort of older adults in the Province of British Columbia from 1997 to 2003. Using a study design of nested case control (case-control study within a cohort), the relative risk of developing PD for statin users was 0.94 (0.82-1.09). Our study did not show a statistically significant effect on the risk of PD with statin use. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Samii, Ali] Univ Washington, Dept Neurol, Seattle VA Parkinson Dis Res Educ & Clin Ctr PADR, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Carleton, Bruce C.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada. [Etminan, Mahyar] Vancouver Hosp, Ctr Clin Epidemiol & Eraluat, Vancouver, BC, Canada. RP Samii, A (reprint author), Univ Washington, Dept Neurol, Seattle VA Parkinson Dis Res Educ & Clin Ctr PADR, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,MS-127, Seattle, WA 98108 USA. EM asamii@u.washington.edu OI /0000-0002-4485-4054 FU American Parkinson Disease Association; William N. and Myriam Pennington Foundation FX This study was funded by the Washington State Chapter of the American Parkinson Disease Association and the William N. and Myriam Pennington Foundation. NR 8 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD NOV PY 2008 VL 15 IS 11 BP 1272 EP 1273 DI 10.1016/j.jocn.2008.01.016 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 367NR UT WOS:000260559200015 PM 18823780 ER PT J AU LaCasce, AS Kho, ME Friedberg, JW Niland, JC Abel, GA Rodriguez, MA Czuczman, MS Millenson, MM Zelenetz, AD Weeks, JC AF LaCasce, Ann S. Kho, Michelle E. Friedberg, Jonathan W. Niland, Joyce C. Abel, Gregory A. Rodriguez, Maria Alma Czuczman, Myron S. Millenson, Michael M. Zelenetz, Andrew D. Weeks, Jane C. TI Comparison of Referring and Final Pathology for Patients With Non-Hodgkin's Lymphoma in the National Comprehensive Cancer Network SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol ID ONCOLOGY-GROUP EXPERIENCE; CLASSIFICATION AB Purpose Before the implementation of the WHO lymphoma classification system, disagreement about pathologic diagnosis was common. We sought to estimate the impact of expert review in the modern era by comparing final pathologic diagnoses at five comprehensive cancer centers with diagnoses assigned at referring centers. Patients and Methods Patients in the National Comprehensive Cancer Network (NCCN) non-Hodgkin's lymphoma (NHL) database with a documented pathologic diagnosis before presentation and a final pathologic diagnosis of any of five common B-cell NHLs were eligible. After central review of discordant cases, we estimated the rate of pathologic concordance, then investigated the etiology of discordance as well its potential impact on prognosis and treatment. Results The overall pathologic discordance rate was 6% (43 of 731 patients; 95% CI, 4% to 8%). For the majority of cases in which the referring diagnosis was apparently final, no additional studies were conducted at the NCCN center, and the change in diagnosis reflected a different interpretation of existing data. Concordance was highest for diffuse large B-cell lymphoma (95%) and follicular lymphoma (FL; grades 1, 2, and not otherwise specified, 95%) and lowest for grade 3 FL (88%). Of the 43 pathologically discordant cases, 81% (35 patients) might have experienced a change in treatment as a result of the pathologic reclassification. Conclusion In the era of the WHO lymphoma classification system, the majority of common B-cell NHLs diagnosed in the community were unchanged by second opinion review by an expert hematopathologist. However, for one patient in 20, there was a discordance in diagnosis that could have altered therapy. J Clin Oncol 26: 5107-5112. (C) 2008 by American Society of Clinical Oncology C1 [LaCasce, Ann S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. Wilmot Canc Ctr, Rochester, NY USA. Roswell Pk Canc Inst, Dept Med, Lymphoma Myeloma Serv, Buffalo, NY 14263 USA. Sloan Kettering Inst, Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, Lymphoma Serv, New York, NY USA. City Hope Natl Med Ctr, Dept Informat Sci, Duarte, CA 91010 USA. Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP LaCasce, AS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ann_lacasce@dfci.harvard.edu OI Zelenetz, Andrew/0000-0003-1403-6883 FU NCI NIH HHS [CA-102216, T32 CA009172] NR 9 TC 46 Z9 47 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2008 VL 26 IS 31 BP 5107 EP 5112 DI 10.1200/JCO.2008.16.4061 PG 6 WC Oncology SC Oncology GA 367FJ UT WOS:000260537600019 PM 18768434 ER PT J AU Culhane, MA Schoenfeld, DA Barr, RS Cather, C Deckersbach, T Freudenreich, O Goff, DC Rigotti, NA Evins, AE AF Culhane, Melissa A. Schoenfeld, David A. Barr, Ruth S. Cather, Corinne Deckersbach, Thilo Freudenreich, Oliver Goff, Donald C. Rigotti, Nancy A. Evins, A. Eden TI Predictors of Early Abstinence in Smokers With Schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SUSTAINED-RELEASE BUPROPION; NICOTINE NASAL SPRAY; SMOKING-CESSATION; DOUBLE-BLIND; TRANSDERMAL NICOTINE; COGNITIVE FUNCTION; CIGARETTE-SMOKING AB Background: In patients with schizophrenia, the smoking cessation rate is low and the burden of smoking-related morbidity and mortality is high. Identification of factors associated with abstinence may allow clinicians to optimize treatment prior to a smoking cessation attempt. Method: To identify factors associated with successful smoking cessation in patients with a DSM-IV diagnosis of schizophrenia, we analyzed baseline data from 114 stable outpatient smokers with schizophrenia who participated in I of 2 smoking cessation trials. The outcome of interest was 4 weeks' continuous abstinence at the end of a 12-week nicotine dependence treatment intervention. Baseline factors associated with abstinence were identified with univariate methods and entered into a manual, forward-selection multivariable regression model to identify independent predictors of abstinence. The study was conducted from March 1999 to February 2004. Results: Fourteen of 114 participants (12%) had biochemically verified 4 weeks' continuous abstinence at week 12. We included 10 non-correlated variables with a univariate association with abstinence in a multivariable model, controlling for pharmacotherapy, age, and gender. Age at initiation of smoking and baseline variability in attentiveness, as measured by Continuous Performance Test-AX (CPT-AX) hit reaction time standard error, were independently associated with abstinence. For every year increase in age at initiation of smoking, the OR for abstinence was 1.36 (95% CI = 1.01 to 1.83), p = .048. For every millisecond decrease in the variability of the reaction time of CPT-AX the OR for achieving abstinence was 1.55 (95% CI = 1.07 to 2.24), p = .021. Conclusion: Later initiation of smoking was associated with increased and baseline attentional impairment with reduced odds of abstinence. Additional research to further our understanding of the relationship between attentional impairment and cigarette smoking in schizophrenia may lead to improved nicotine dependence treatments for this group. C1 [Evins, A. Eden] Massachusetts Gen Hosp, Schizophrenia Res Program, Addict Res Program, Freedom Trail Clin, Boston, MA 02114 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Deckersbach, Thilo] Massachusetts Gen Hosp, Psychiat Neurosci Div, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Schizophrenia Res Program, Addict Res Program, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU Department of Health and Human Services Substance Abuse Mental Health Services Administration [05BIMACMHS-04]; National Institute oil Drug Abuse [K23 DA00510]; National Institute of Mental Health [K24 MH02025]; National Heart, Lung, and Blood Institute [K24 HL04440]; German Academic Exchange Service; Tourette Syndrome Association; Obsessive Compulsive Foundation; National Alliance for Research on Schizophrenia and Depression; Clinical Research and Training Program, Janssen; National Institute of Mental Health; Primedia and Reed Elsevier; Pfizer; Xenoport; Dainippon Sumitomo; Solvay-Wyeth; Bristol-Myers Squibb; VerusMed; Letters and Science; SG Cowen; Vista Research; Organon; Proteus; Genactics; Forest; Xytis; MedReviews; Eli Lilly; Vanda Pharmaceuticals; Sanofi-Aventis; Nabi Biopharmaceuticals FX This work was supported by Department of Health and Human Services Substance Abuse and Mental Health Services Administration grant 05BIMACMHS-04 (Dr. Evins), National Institute oil Drug Abuse grant K23 DA00510 (Dr, Evins), National Institute of Mental Health grant K24 MH02025 (Dr. Goff), and National Heart, Lung, and Blood Institute grant K24 HL04440 (Dr. Rigotti).; Financial disclosure: Dr. Deckersbach is an employee of Massachusetts General Hospital; is a consultant to MEDACorp; and has received research support from the German Academic Exchange Service, Tourette Syndrome Association, Obsessive Compulsive Foundation, National Alliance for Research on Schizophrenia and Depression, Clinical Research and Training Program, Janssen, National Institute of Mental Health, and Forest. Dr. Freudenreich has received grant/research support from Cephalon and has received honoraria from Primedia and Reed Elsevier. Dr. Goff has received honoraria or research support from Pfizer, Cephalon. and Janssen and has received honoraria from Xenoport., Dainippon Sumitomo, Solvay-Wyeth, Bristol-Myers Squibb, VerusMed, Letters and Science, Primedia, SG Cowen, Vista Research, Organon, Proteus, Genactics, Forest, Xytis, MedReviews, Eli Lilly, and Vanda Pharmaceuticals. Dr. Rigotti has been a consultant to Pfizer and has received grant/research support from Pfizer, Sanofi-Aventis, and Nabi Biopharmaceuticals. Dr. Evins has received grant/research support from National Institute on Drug Abuse and research product support from Pfizer and has received honoraria from Primedia and Reed Elsevier. Drs. Schoenfeld, Barr, and Cather and Ms. Culhane report no additional financial or other relationships relevant to the subject of this article. NR 83 TC 22 Z9 22 U1 7 U2 8 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 NOV PY 2008 VL 69 IS 11 BP 1743 EP 1750 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 378VE UT WOS:000261351800009 PM 19026259 ER PT J AU Spencer, TJ Landgraf, JM Adler, LA Weisler, RH Anderson, CS Youcha, SH AF Spencer, Thomas J. Landgraf, Jeanne M. Adler, Lenard A. Weisler, Richard H. Anderson, Colleen S. Youcha, Sharon H. TI Attention-Deficit/Hyperactivity Disorder-Specific Quality of Life With Triple-Bead Mixed Amphetamine Salts (SPD465) in Adults: Results of a Randomized, Double-Blind, Placebo-Controlled Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID EXTENDED-RELEASE; SCALE AAQOL; ADHD; ATOMOXETINE; ADOLESCENTS; CHILDREN; MULTICENTER AB Objective: To assess the quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) given triple-bead mixed amphetamine salts (MAS), a long-acting amphetamine formulation designed for a duration of action of up to 16 hours. Method: 274 adults with ADHD (DSM-IV-TR criteria) were randomly assigned to 7 weeks of double-blind treatment with an optimal dose of triple-bead MAS (12.5 mg to 75 mg) (N = 137) or placebo (N = 137). As a secondary objective of this study, QOL was assessed on the basis of self-reported Adult ADHD Impact Module (AIM-A) scores, describing ADHD-specific QOL in 6 domains and global QOL (questions 1-4). To assess safety, data were collected on adverse events, vital signs, electrocardiograms, laboratory tests, and sleep quality. The trial was conducted from January 2005 to June 2005. Results: Statistically significant improvement between triple-bead MAS and placebo was observed in all 6 ADHD-specific AIM-A subscales. In addition, statistically significant improvement in global QOL between triple-bead MAS and placebo was seen, based on AIM-A question 1 (p = .0006) and question 4 (p = .0001). Patients' age, gender, race, and prior use of stimulant medication were not found to significantly affect AIM-A subscale scores. The most common treatment-emergent adverse events with triple-bead MAS (insomnia, dry mouth, decreased appetite, headache, and weight decreased) were consistent with amphetamine treatment. and their incidence generally decreased with time. Conclusions: Adults with ADHD showed significantly improved QOL for both ADHD-specific and global measures with triple-bead MAS in comparison to placebo, based on AIM-A scores. Treatment-emergent adverse events were mostly mild to moderate in intensity and were consistent with amphetamine treatment. Trial Registration: clinicaltrials.gov Identifier: NCT00150579 C1 [Spencer, Thomas J.] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Dept Psychiat, Boston, MA 02114 USA. [Spencer, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Landgraf, Jeanne M.] HealthAciCHQ Inc, Boston, MA USA. [Adler, Lenard A.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Weisler, Richard H.] Duke Univ, Dept Psychiat, Raleigh, NC USA. [Weisler, Richard H.] Univ N Carolina, Dept Psychiat, Raleigh, NC USA. [Anderson, Colleen S.; Youcha, Sharon H.] Shire Dev Inc, Wayne, PA USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Dept Psychiat, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM spencer@helix.mgh.harvard.edu FU Shire Development Inc.; Shire; Eli Lilly; GlaxoSmithKline; Pfizer; McNeil; Cephalon; Janssen; Novartis; National Institute of Mental Health (NIMH); Cortex; Ortho-McNeil/Janssen/Johnson Johnson; Abbott; Merck; Bristol-Myers Squibb; National Institute on Drug Abuse; New River; Sanofi-Aventis; Psychogenics; AstraZeneca; Biovail; Burroughs Wellcome; Ciba Geigy; CoMentis; Corcept; Eisai; Forest; Lundbeck; Medicinova; Neurochem; Organon; Otsuka; Pharmacia; Saegis; Sanofi; Sanofi-Synthelabo; Schwabe/Ingenix; Solvay; Synaptic; TAP; UCB Pharma; Vela; Wyeth FX Supported by funding from Shire Development Inc.; Financial disclosure: Dr. Spencer has received research support from, is a speaker for, or is on the advisory board of Shire, Eli Lilly, GlaxoSmithKline, Pfizer, McNeil, Cephalon, Janssen, Novartis. and the National Institute of Mental Health (NIMH). Dr. Adler has received research support from Eli Lilly, Cortex. Cephalon, Pfizer, Novartis, Ortho-McNeil/Janssen/Johnson & Johnson. Abbott, Merck, Bristol-Myers Squibb, National Institute on Drug Abuse, New River, and Shire; is a member of the speakers bureaus for Eli Lilly and Shire: and is a member of the speakers/advisory boards and a consultant for Eli Lilly, Cortex. Cephalon, Pfizer, Novartis, Ortho-McNeil/Janssen/Johnson & Johnson, Abbott, Merck, New River, Organon, Sanofi-Aventis, Psychogenics. Mindsite. and Shire. Dr. Weisler is or has been a consultant to, oil the speakers bureaus of, and/or received research support from NIMH. Abbott, AstraZeneca, Biovail, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Ciba Geigy, CoMentis, Corcept, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson. Lundbeck, McNeil, Medicinova, Merck, Neurochem, New River, Novartis. Organon. Otsuka, Pfizer, Pharmacia, Saegis, Sanofi, Sanofi-Synthelabo, Schwabe/Ingenix, Shire, Solvay, Synaptic, TAP. UCB Pharma, Vela, and Wyeth and is or has been a stock shareholder of Merck, Pfizer, Cortex, and Bristol-Myers Squibb. Ms. Anderson and Dr. Youcha are employees of Shire and report no additional financial or other relationships relevant to the subject of this article. Ms. Landgraf reports no additional financial or other relationships relevant to the subject of this article. NR 26 TC 19 Z9 19 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2008 VL 69 IS 11 BP 1766 EP 1775 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 378VE UT WOS:000261351800012 PM 19026251 ER PT J AU Sitnikova, T Holcomb, PJ Kiyonaga, KA Kuperberg, GR AF Sitnikova, Tatiana Holcomb, Phillip J. Kiyonaga, Kristi A. Kuperberg, Gina R. TI Two Neurocognitive Mechanisms of Semantic Integration during the Comprehension of Visual Real-world Events SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID PRIMATE PREFRONTAL CORTEX; BRAIN POTENTIALS; RIGHT-HEMISPHERE; ELECTROPHYSIOLOGICAL EVIDENCE; LANGUAGE COMPREHENSION; SENTENCE COMPREHENSION; THEMATIC RELATIONSHIPS; DISCOURSE; CONTEXT; MEMORY AB How do comprehenders build up overall meaning representations of visual real-world events? This question was examined by recording event-related potentials (ERPs) while participants viewed short, silent movie clips depicting everyday events. In two experiments, it was demonstrated that presentation of the contextually inappropriate information in the movie endings evoked an anterior negativity. This effect was similar to the N400 component whose amplitude has been previously reported to inversely correlate with the strength of semantic relationship between the context and the eliciting stimulus in word and static picture paradigms. However, a second, somewhat later, ERP component-a posterior late positivity-was evoked specifically when target objects presented in the movie endings violated goal-related requirements of the action constrained by the scenario context (e. g., an electric iron that does not have a sharp-enough edge was used in place of a knife in a cutting bread scenario context). These findings suggest that comprehension of the visual real world might be mediated by two neurophysiologically distinct semantic integration mechanisms. The first mechanism, reflected by the anterior N400-like negativity, maps the incoming information onto the connections of various strengths between concepts in semantic memory. The second mechanism, reflected by the posterior late positivity, evaluates the incoming information against the discrete requirements of real-world actions. We suggest that there may be a tradeoff between these mechanisms in their utility for integrating across people, objects, and actions during event comprehension, in which the first mechanism is better suited for familiar situations, and the second mechanism is better suited for novel situations. C1 [Sitnikova, Tatiana] Massachusetts Gen Hosp, Dept Psychiat, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sitnikova, Tatiana] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Holcomb, Phillip J.; Kiyonaga, Kristi A.; Kuperberg, Gina R.] Tufts Univ, Medford, MA 02155 USA. RP Sitnikova, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149 2301,13th St, Charlestown, MA 02129 USA. EM tatiana@nmr.mgh.harvard.edu FU MGH Fund for Medical Discovery; Sidney R. Baer, Jr., Foundation [MH02034, MH071635]; Institute for Mental Illness and Neuroscience Discovery ( MIND); [HD25889] FX This research was conducted in partial fulfillment of the requirements for the PhD degree at Tufts University, August 2003. Tatiana Sitnikova thanks the dissertation committee chair, Phillip J. Holcomb, as well as the other members of the dissertation committee, W. Caroline West, Gina Kuperberg, and Lisa Shin for their stimulating contributions. We thank David R. Hughes and Sonya Jairaj for their assistance in preparing the materials and collecting the data. This research was supported by a grant HD25889 to P. J. H., a grant from the MGH Fund for Medical Discovery to T. S., NARSAD (with the Sidney R. Baer, Jr., Foundation) grants to T. S. and G. K., grants MH02034 and MH071635 to G. K., and by the Institute for Mental Illness and Neuroscience Discovery (MIND). NR 63 TC 69 Z9 71 U1 1 U2 13 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD NOV PY 2008 VL 20 IS 11 BP 2037 EP 2057 DI 10.1162/jocn.2008.20143 PG 21 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 360GM UT WOS:000260046000010 PM 18416681 ER PT J AU Prasad, SR Sahani, DV Mino-Kenudson, M Narra, VR Menias, C Wang, HL Middleton, WD Chintapalli, KN AF Prasad, Srinivasa R. Sahani, Dushyant V. Mino-Kenudson, Mari Narra, Vamsi R. Menias, Christine Wang, Hanlin L. Middleton, Willian D. Chintapalli, Kedar N. TI Benign Hepatic Neoplasms: An Update on Cross-Sectional Imaging Spectrum SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Review DE liver; neoplasms; CT scan; magnetic resonance imaging; ultrasound ID FOCAL NODULAR HYPERPLASIA; RADIOLOGIC-PATHOLOGICAL CORRELATION; CONTRAST-ENHANCED MRI; FLUID-FLUID LEVELS; BILE-DUCT ADENOMA; HEPATOCELLULAR ADENOMA; LIVER-LESIONS; MANGAFODIPIR-TRISODIUM; BILIARY PAPILLOMATOSIS; SPIRAL CT AB Benign hepatic neoplasms constitute a heterogeneous group of neoplasms with characteristic histology and variable tumor biology. Based on the cell of origin, benign hepatic neoplasms are classified into epithelial, nonepithelial, and miscellaneous categories according to the 2000 World Health Organization classification system. Benign hepatic neoplasms demonstrate a wide spectrum of imaging findings that reflect the histomorphologic changes. Some neoplasms show pathognomic imaging findings that permit accurate characterization and optimal management. C1 [Prasad, Srinivasa R.; Chintapalli, Kedar N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Narra, Vamsi R.; Menias, Christine; Middleton, Willian D.] Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO USA. [Wang, Hanlin L.] Washington Univ, Dept Pathol, St Louis, MO 63130 USA. RP Prasad, SR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM prasads@uthscsa.edu NR 71 TC 4 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2008 VL 32 IS 6 BP 829 EP 840 DI 10.1097/RCT.0b013e31815a5748 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 379MB UT WOS:000261399300001 PM 19204440 ER PT J AU Kantaputra, P Miletich, I Ludecke, HJ Suzuki, EY Praphanphoj, V Shivdasani, R Wuelling, M Vortkamp, A Napierala, D Sharpe, PT AF Kantaputra, P. Miletich, I. Luedecke, H.-J. Suzuki, E. Y. Praphanphoj, V. Shivdasani, R. Wuelling, M. Vortkamp, A. Napierala, D. Sharpe, P. T. TI Tricho-Rhino-Phalangeal Syndrome with Supernumerary Teeth SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE Tricho-rhino-phalangeal syndrome; TRPS1; tooth development; supernumerary teeth ID RHINO-PHALANGEAL-SYNDROME; LANGER-GIEDION-SYNDROME; SYNDROME TYPE-I; SYNDROME TYPE-III; MENTAL-RETARDATION; MUTATIONS; DELETION; PROTEIN; TRPS1; EXOSTOSES AB Tricho-rhino-phalangeal syndromes (TRPS) are caused by mutation or deletion of TRPS1, a gene encoding a GATA transcription factor. These disorders are characterized by abnormalities of the hair, face, and selected bones. Rare cases of individuals with TRPS displaying supernumerary teeth have been reported, but none of these has been examined molecularly. We used two different approaches to investigate a possible role of TRPS1 during tooth development. We looked at the expression of Tprs1 during mouse tooth development and analyzed the craniofacial defects of Trps1 mutant mice. In parallel, we investigated whether a 17-year-old Thai boy with clinical features of TRPS and 5 supernumerary teeth had mutation in TRPS1. We report here that Trps1 is expressed during mouse tooth development, and that an individual with TRPS with supernumerary teeth has the amino acid substitution A919V in the GATA zinc finger of TRPS1. These results suggest a role for TRPS1 in tooth morphogenesis. C1 [Miletich, I.; Sharpe, P. T.] Kings Coll London, Biomed Res Ctr, Inst Dent, Dept Craniofacial Dev, London WC2R 2LS, England. [Kantaputra, P.] Chiang Mai Univ, Fac Dent, Dept Pediat Dent, Chiang Mai, Thailand. [Luedecke, H.-J.] Univ Klinikum Essen, Inst Humangenet, Essen, Germany. [Suzuki, E. Y.] Chiang Mai Univ, Fac Dent, Dept Orthodont, Chiang Mai, Thailand. [Praphanphoj, V.] Rajanukul Inst, Genet Lab, Bangkok, Thailand. [Shivdasani, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wuelling, M.; Vortkamp, A.] Univ Duisburg Essen, Ctr Med Biotechnol, Dept Dev Biol, Essen, Germany. [Napierala, D.] Baylor Coll Med, Houston, TX 77030 USA. RP Sharpe, PT (reprint author), Kings Coll London, Biomed Res Ctr, Inst Dent, Dept Craniofacial Dev, London WC2R 2LS, England. EM paul.sharpe@kcl.ac.uk FU Thailand Research Fund (TRF); Research Councils UK (RCUK); Deutsche Forschungsgemeinschaft (DFG) FX We are grateful to the participant and his family for allowing us to use his medical and dental information for publication. The research is supported by The Thailand Research Fund (TRF) to P. K., Research Councils UK (RCUK) to I. M., and the Deutsche Forschungsgemeinschaft (DFG) to H.-J.L. NR 30 TC 10 Z9 13 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2008 VL 87 IS 11 BP 1027 EP 1031 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 363HU UT WOS:000260259200006 PM 18946009 ER PT J AU Tsuchiya, M Tye, CE Sharma, R Smith, CE Bartlett, JD AF Tsuchiya, M. Tye, C. E. Sharma, R. Smith, C. E. Bartlett, J. D. TI XBP1 May Determine the Size of the Ameloblast Endoplasmic Reticulum SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE X-box-binding-protein-1; enamel development; organelle volume ID UNFOLDED PROTEIN RESPONSE; PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1; DENTAL ENAMEL FORMATION; MESSENGER-RNA; PHOSPHOLIPID BIOSYNTHESIS; RAT INCISOR; ER STRESS; BIOGENESIS; IRE1 AB Ameloblasts progress through defined stages of development as enamel forms on teeth. Pre-secretory ameloblasts give rise to tall columnar secretory ameloblasts that direct the enamel to achieve its full thickness. During the maturation stage, the ameloblasts shorten and direct the enamel to achieve its final hardened form. Here we ask how the volume of selected ameloblast organelles changes (percent volume per ameloblast) as ameloblasts progress through six defined developmental stages. We demonstrate that mitochondria volume peaks during late maturation, indicating that maturation-stage ameloblasts maintain a high level of metabolic activity. Also, the endoplasmic reticulum (ER) volume changes significantly as a function of developmental stage. This prompted us to ask if X-box-binding protein-1 (XBP1) plays a role in regulating ameloblast ER volume, as has been previously demonstrated for secretory acinar cells and for plasma cell differentiation. We demonstrate that Xbp1 expression correlates positively with percent volume of ameloblast ER. C1 [Tsuchiya, M.; Tye, C. E.; Sharma, R.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. [Tsuchiya, M.; Tye, C. E.; Sharma, R.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Tsuchiya, M.] Tohoku Univ, Grad Sch Dent, Div Aging & Geriatr Dent, Sendai, Miyagi 9808575, Japan. [Smith, C. E.] Univ Montreal, Fac Med Dent, Lab Study Calcified Tissues & Biomat, Montreal, PQ H3C 3J7, Canada. RP Bartlett, JD (reprint author), Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Sharma, Ramaswamy/F-8401-2012; Testes, Olga/E-8912-2013; OI Tsuchiya, Masahiro/0000-0002-7000-4547 FU NIDCR [DE016276] FX We thank Dr. Fumihiko Urano for providing anti-phospho IRE1 antisera. This work was supported by NIDCR grant DE016276 (to JDB). NR 25 TC 3 Z9 4 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2008 VL 87 IS 11 BP 1058 EP 1062 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 363HU UT WOS:000260259200012 PM 18946015 ER PT J AU Kabrhel, C AF Kabrhel, Christopher TI OUTCOMES OF HIGH PRETEST PROBABILITY PATIENTS UNDERGOING D-DIMER TESTING FOR PULMONARY EMBOLISM: A PILOT STUDY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE pulmonary embolism; venous thromboembolism; D-dimer; ELISA; pretest probability ID EMERGENCY-DEPARTMENT PATIENTS; VENOUS THROMBOSIS; CLINICAL-MODEL; MANAGEMENT; UTILITY; SCORE AB ELISA (enzyme-linked immunosorbent assay) D-dimer testing is commonly used in the evaluation of possible pulmonary embolism (PE) in the emergency department, but is not recommended in high pretest probability patients. Whether a negative ELISA D-dimer can safely rule out PE in these patients is not known, as there have been no large studies comparing ELISA D-dimer results and outcomes in high pretest probability patients. This was a prospective observational pilot study of emergency department patients evaluated for PE. Patients evaluated for PE had pretest probability assessed by the Wells PE Score. High pretest probability was defined as: dichotomized Wells Score > 4 points and patients with trichotomized Wells Score > 6 points. Patients had an ELISA D-dimer ordered by the treating physician. Pulmonary embolism was defined as: positive computed tomography scan, high probability ventillation/perfusion scan, positive pulmonary angiogram, or PE on 3-month follow-up. We calculated sensitivity, specificity, positive and negative predictive value, and likelihood ratios for the ELISA D-dimer. We prospectively enrolled 541 patients who underwent D-dimer testing for PE, of whom 130 patients had Wells Score > 4 and 33 patients bad Wells Score > 6 (not mutually exclusive). Of subjects with Wells Score > 4, 23 (18%) were diagnosed with PE and 40 (31%) had a negative D-dimer. No patient with Wells Score > 4 (sensitivity 100%, 95% confidence interval [CI] 82%-100%; specificity 37%, 95% CI 28%-47%) or Wells Score > 6 (sensitivity 100%, 95% CI 63%-100%; specificity 56%, 95% CI 35%-76%) who had a negative D-dimer was diagnosed with PE. The likelihood ratio for a negative D-dimer was 0 fort both the Wells > 4, and Wells > 6 groups, however, the upper limits of the confidence interval around the post-test probability for PE were 16% and 33%, respectively, for these high probability groups. In this pilot study, the rapid ELISA D-dimer had high sensitivity and negative predictive value even when applied to patients with high pretest probability for PE. However, with the post-test probability of PE still as high as 16-33% in the negative D-dimer groups, this precludes applying the results to patient care at present. Further testing is warranted to determine whether these findings can be safely incorporated into practice. (C) 2008 Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Kabrhel, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. OI Kabrhel, Christopher/0000-0002-8699-7176 NR 23 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2008 VL 35 IS 4 BP 373 EP 377 DI 10.1016/j.jemermed.2007.08.070 PG 5 WC Emergency Medicine SC Emergency Medicine GA 373PJ UT WOS:000260983900005 PM 18343077 ER PT J AU Almawi, W Tamim, H Al-Sayed, N Arekat, MR Al-Khateeb, GM Baqer, A Tutanji, H Kamel, C AF Almawi, W. Tamim, H. Al-Sayed, N. Arekat, M. R. Al-Khateeb, G. M. Baqer, A. Tutanji, H. Kamel, C. TI Association of comorbid depression, anxiety, and stress disorders with Type 2 diabetes in Bahrain, a country with a very high prevalence of Type 2 diabetes SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE Anxiety; Bahrain; DASS-21; depression; stress; Type 2 diabetes ID RISK-FACTOR; INSULIN-RESISTANCE; AFRICAN-AMERICANS; GLYCEMIC CONTROL; SCALES DASS; ADULTS; METAANALYSIS; POPULATION; SYMPTOMS; COMPLICATIONS AB This study examined the association of depression, anxiety, and stress with Type 2 diabetes (T2DM) in Bahrain, an island-country with a very high prevalence of T2DM. This was a cross-sectional study involving administering Depression Anxiety Stress Scales (DASS)-21 structured depression, anxiety, and stress scale to 143 T2DM patients and 132 healthy controls. Higher proportion of T2DM patients were found in the mild-moderate and severe-extremely severe depression (p=0.002), anxiety (p<0.001), and stress (p<0.001) groups. Chronic disease and disease duration were significantly associated with the 3 disturbances, while employment status was associated with anxiety and depression. Logistic regression analysis showed that anxiety, depression, and stress were associated with T2DM after adjusting for all variables, while age was the only significant variable associated with stress. These results suggest a positive contribution of T2DM to increased depressive and/or anxiety and/or stress disorders among the patients examined, thereby recommending counseling for T2DM patients. (J. Endocrinol. Invest. 31: 1020-1024, 2008) (C) 2008, Editrice Kurtis C1 [Almawi, W.] Arabian Gulf Univ, Coll Med & Med Sci, Dept Med Biochem, Manama, Bahrain. [Tamim, H.] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada. [Al-Sayed, N.; Arekat, M. R.; Tutanji, H.] Joslin Diabet Ctr, Manama, Bahrain. RP Almawi, W (reprint author), Arabian Gulf Univ, Coll Med & Med Sci, Dept Med Biochem, POB 22979, Manama, Bahrain. EM wassim@agu.edu.bh NR 45 TC 29 Z9 31 U1 4 U2 15 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD NOV PY 2008 VL 31 IS 11 BP 1020 EP 1024 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 401CQ UT WOS:000262916300014 PM 19169060 ER PT J AU Chae, DH Takeuchi, DT Barbeau, EM Bennett, GG Lindsey, JC Stoddard, AM Krieger, N AF Chae, D. H. Takeuchi, D. T. Barbeau, E. M. Bennett, G. G. Lindsey, J. C. Stoddard, A. M. Krieger, N. TI Alcohol disorders among Asian Americans: associations with unfair treatment, racial/ethnic discrimination, and ethnic identification (the national Latino and Asian Americans study, 2002-2003) SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID WORLD-HEALTH-ORGANIZATION; MENTAL-HEALTH; PERCEIVED DISCRIMINATION; ALDEHYDE DEHYDROGENASE; RACIAL-DISCRIMINATION; DRINKING PATTERNS; UNITED-STATES; IDENTITY; STRESS; ABUSE AB Study objective: To examine history of alcohol abuse/dependence disorder in relation to unfair treatment, racial/ethnic discrimination, and ethnic identification among Asian Americans. Design: Weighted multivariate analyses of cross-sectional national survey data predicting lifetime history of alcohol abuse/dependence disorders. Setting: USA, Asian Americans. Participants: 2007 Asian American adults recruited to the National Latino and Asian American Study (NLAAS; 2002-2003). Results: Controlling for sociodemographic characteristics, Asian Americans who reported experiencing unfair treatment had higher odds of history of alcohol abuse/dependence disorder (OR 5.26, 95% CI 1.90 to 14.56). Participants who reported high levels of ethnic identification had lower odds of history of alcohol abuse/dependence disorders (OR 0.46, 95% CI 0.23 to 0.90). Ethnic identification moderated the influence of racial/ethnic discrimination (p = 0.097). Among participants with low levels of ethnic identification, racial/ethnic discrimination was associated with greater odds of having a history of alcohol disorder compared with those with high levels of ethnic identification. Conclusions: Social hazards such as unfair treatment and racial/ethnic discrimination should be considered in the development of programmes addressing alcohol disorders among Asian Americans. Interventions that promote ethnic identification in this population may be particularly relevant in mitigating the negative influence of racial/ethnic discrimination on alcohol disorders. C1 [Chae, D. H.] Univ Calif San Francisco, Ctr Hlth & Community, San Francisco, CA 94118 USA. [Chae, D. H.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Takeuchi, D. T.] Univ Washington, Seattle, WA 98195 USA. [Barbeau, E. M.; Bennett, G. G.; Krieger, N.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Barbeau, E. M.; Bennett, G. G.] Dana Farber Canc Inst, Hlth Ctr Community Based Res, Boston, MA 02115 USA. [Lindsey, J. C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Stoddard, A. M.] New England Res Inst, Watertown, MA 02172 USA. RP Chae, DH (reprint author), Univ Calif San Francisco, Ctr Hlth & Community, 3333 Calif St,Suite 465,Campus Box 0844, San Francisco, CA 94118 USA. EM dhchae@post.harvard.edu RI Chae, David/F-6956-2015 FU National Institute of Mental Health (NIMH [U01 MH062209, U01 MH 62207]; Office of Behavioral and Social Sciences Research; Substance Abuse and Mental Health Services Agency; W. K. Kellogg Doctoral Fellowship in Health Policy FX The National Latino and Asian American Study is supported by the National Institute of Mental Health (NIMH; grant U01 MH062209 for M Alegria, PI, and U01 MH 62207 for DTT, PI) with supplemental support from the Office of Behavioral and Social Sciences Research, Substance Abuse and Mental Health Services Agency, and the Latino Research Program Project P01 MH059876. DHC was also supported by the W. K. Kellogg Doctoral Fellowship in Health Policy. NR 50 TC 51 Z9 52 U1 3 U2 5 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 NOV PY 2008 VL 62 IS 11 BP 973 EP 979 DI 10.1136/jech.2007.066811 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 359VV UT WOS:000260017100009 PM 18854501 ER PT J AU Sonnenberg, A AF Sonnenberg, A. TI Environmental influence in ulcerative colitis starts in early childhood SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID CROHNS-DISEASE; TIME TRENDS; PEPTIC-ULCER; MORTALITY; COHORT; PERIOD AB Aims: The present analysis served to address the question at what age environmental factors start to exert their influence on the occurrence of ulcerative colitis. Methods: Mortality data from 21 different countries were accumulated between 1941 and 2004 to analyse the variation of age-specific death rates during consecutive time periods and among different countries. Results: Between 1941 and 2004 the trends of mortality from ulcerative colitis among different age groups formed a fan-like pattern with a progressively steeper decline of mortality among increasingly younger age groups. This general pattern included mortality in all age groups older than 5 years, but was absent in the youngest age group, 0-4 years. In countries with frequent occurrence of ulcerative colitis, high mortality from ulcerative colitis affected different age groups alike. This pattern was reflected by a set of statistically significant correlations between the mortality of each two consecutive age groups from different countries. The progression of significant correlations among consecutive age groups broke off only when the geographic variations of the age groups 0-4 and 5-9 years were compared. Conclusions: The analysis suggests that environmental factors responsible for the temporal and geographic variations of ulcerative colitis start to exert their influence during early childhood. C1 Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 11 TC 7 Z9 7 U1 0 U2 1 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 NOV PY 2008 VL 62 IS 11 BP 992 EP 994 DI 10.1136/jech.2007.067256 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 359VV UT WOS:000260017100012 PM 18854504 ER PT J AU Bilimoria, KY Bentrem, DJ Merkow, RP Nelson, H Wang, E Ko, CY Soper, NJ AF Bilimoria, Karl Y. Bentrem, David J. Merkow, Ryan P. Nelson, Heidi Wang, Edward Ko, Clifford Y. Soper, Nathaniel J. TI Laparoscopic-assisted vs. Open Colectomy for Cancer: Comparison of Short-term Outcomes from 121 Hospitals SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract/Digestive Disease Week CY MAY 17-21, 2008 CL San Diego, CA SP Soc Surg Alimentary Tract DE Colon cancer; Colectomy; Laparoscopy; Cancer; Surgery; National Surgical Quality Improvement Program ID RANDOMIZED CONTROLLED-TRIAL; SEGMENTAL COLON RESECTION; COLORECTAL-CANCER; PATIENT OUTCOMES; SURGERY; CERTIFICATION; METAANALYSIS; EXPERIENCE; CARCINOMA AB Background Overall postoperative morbidity and mortality after laparoscopic-assisted colectomy (LAC) and open colectomy (OC) have been shown to be generally comparable; however, differences in the occurrence of specific complications are unknown. The objective of this study was to determine whether certain complications occurred more frequently after LAC vs. OC for colon cancer. Methods Using the American College of Surgeons-National Surgical Quality Improvement Project's (ACS-NSQIP) participant-use file, patients were identified who underwent colectomy for cancer at 121 participating hospitals in 2005-2006. Multiple logistic regression models including propensity scores were developed to assess the risk-adjusted association between surgical approach (LAC vs. OC) and 30-day outcomes. Patients were excluded if they underwent emergent procedures, were ASA class 5, or had metastatic disease. Results Of the 3,059 patients who underwent elective colectomy for cancer, 837 (27.4%) underwent LAC and 2,222 (72.6%) underwent OC. There were no significant differences in age, comorbidities, ASA class, or body mass index (BMI) between patients undergoing LAC vs. OC. Patients undergoing LAC had a lower likelihood of developing any adverse event compared to OC (14.6% vs. 21.7%; OR 0.64, 95% CI 0.51-0.81, P<0.0001), specifically surgical site infections, urinary tract infections, and pneumonias. Mean length of stay was significantly shorter after LAC vs. OC (6.2 vs. 8.7 days, P<0.0001). There were no differences between LAC and OC in the reoperation rate (5.5% vs. 5.8%, P=0.79) or 30-day mortality (1.4% vs. 1.8%, P=0.53). Conclusions Laparoscopic-assisted colectomy was associated with lower morbidity compared to OC in select patients, specifically for infectious complications. C1 [Bilimoria, Karl Y.; Bentrem, David J.; Wang, Edward; Soper, Nathaniel J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Colorado, Sch Med, Dept Surg, Denver, CO 80202 USA. [Nelson, Heidi] Mayo Clin, Dept Surg, Rochester, MN USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Dept Surg, Feinberg Sch Med, 251 E Huron St,Galter 3-150, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu NR 33 TC 67 Z9 70 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD NOV PY 2008 VL 12 IS 11 BP 2001 EP 2009 DI 10.1007/s11605-008-0568-x PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 363QQ UT WOS:000260282200032 PM 18575941 ER PT J AU Werner, RM Chang, VW AF Werner, Rachel M. Chang, Virginia W. TI The Relationship Between Measured Performance and Satisfaction with Care Among Clinically Complex Patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE measured performance; patient satisfaction; clinically complex patients ID QUALITY-OF-CARE; MENTAL-HEALTH-CARE; TECHNICAL QUALITY; UNINTENDED CONSEQUENCES; PSYCHOMETRIC PROPERTIES; MEDICAL-CARE; GUIDELINES; SERVICES; OUTCOMES; RISK AB BACKGROUND: Recent work has shown that clinically complex patients are more likely to receive recommended care, but it is unknown whether higher achievement on individual performance goals results in improved care for complex patients or detracts from other important but unmeasured aspects of care, resulting in unmet needs and lower satisfaction with care. OBJECTIVE: To examine the relationship between measured performance and satisfaction with care among clinically complex patients DESIGN AND PARTICIPANTS: An observational analysis of a national sample of 35,927 veterans included in the External Peer Review Program in fiscal years 2003 and 2004. MEASUREMENTS: First, compliance with individual performance measures (breast cancer screening with mammography, colorectal cancer screening, influenza vaccination, pneumococcal vaccination, lipid monitoring, use of ACE inhibitor in heart failure, and diabetic eye examination), as well as overall receipt of recommended care, was estimated as a function of each patient's clinical complexity. Second, global satisfaction with care was estimated as a function of clinical complexity and compliance with performance measures. MAIN RESULTS: Higher clinical complexity was predictive of slightly higher overall performance (OR 1.13, 95% CI 1.09 to 1.18) and higher performance on most individual performance measures, an effect that was mediated by increased visit frequency. High measured performance was associated with higher satisfaction with care among patients with high clinical complexity. In fact, as complexity increased, the effect of achieving high performance on the odds of being satisfied with care also increased CONCLUSIONS: Not only was measured performance higher in clinically complex patients, but satisfaction with care was also higher among clinically complex patients with high measured performance, suggesting that compliance with performance measures in clinically complex patients does not crowd out unmeasured care. C1 [Werner, Rachel M.; Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.; Chang, Virginia W.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.; Chang, Virginia W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. RP Werner, RM (reprint author), 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@mail.med.upenn.edu FU Center for Health Equity Research and Promotion, Philadelphia VA; Atlantic Philanthropies, SGIM/ACGIM; John A. Hartford Foundation; VA HSR&D Career Development Award. Virginia Chang; NIH/NICHD [K12-HD043459] FX Funding for the study was provided by the Center for Health Equity Research and Promotion, Philadelphia VA and by the Atlantic Philanthropies, SGIM/ACGIM, the John A. Hartford Foundation, and ASP. Rachel Werner is supported in part by a VA HSR&D Career Development Award. Virginia Chang is supported in part by grant K12-HD043459 from the NIH/NICHD. NR 43 TC 13 Z9 13 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2008 VL 23 IS 11 BP 1729 EP 1735 DI 10.1007/s11606-008-0734-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 379VI UT WOS:000261423900001 PM 18649107 ER PT J AU Schane, RE Woodruff, PG Dinno, A Covinsky, KE Walter, LC AF Schane, Rebecca E. Woodruff, Prescott G. Dinno, Alexis Covinsky, Ken E. Walter, Louise C. TI Prevalence and Risk Factors for Depressive Symptoms in Persons with Chronic Obstructive Pulmonary Disease SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic obstructive pulmonary disease (COPD); depressive symptoms; risk factors ID QUALITY-OF-LIFE; ACUTE EXACERBATION; HEALTH-STATUS; OLDER WOMEN; SELF-REPORT; COPD; MORTALITY; ANXIETY; IMPACT; ASSOCIATION AB BACKGROUND: Although depression is a risk factor for adverse outcomes in chronic illness, little is known about the prevalence or risk factors for depressive symptoms in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine the prevalence of depressive symptoms in COPD as compared to other chronic illnesses and to identify risk factors for depressive symptoms in COPD. DESIGN AND PATIENTS: Cross-sectional study of 18,588 persons (1,736 subjects with self-reported COPD), representing a sample of the US population aged >= 50 years who participated in the 2004 Health and Retirement Survey. MEASUREMENTS: Presence of COPD and other chronic conditions was defined by self-report. Presence of depressive symptoms was assessed using the CES-D8 scale. Participants with a score >= 3 on CES-D8 were classified as having clinically significant depressive symptoms. MAIN RESULTS: Of 1,736 participants with COPD, 40% had >= 3 depressive symptoms. Depressive symptoms were more common in COPD than in coronary heart disease, stroke, diabetes, arthritis, hypertension, and cancer. Risk factors for >= 3 depressive symptoms in COPD: younger age (OR 1.02/per year younger, 95% CI[1.02-1.03]), female gender (1.2[1.1-1.3]), current smoking (1.5[1.3-1.7]), marital status[divorced/separated (1.8[1.6-2.1]), widowed (1.8[1.6-2]), never married (1.4[1.1-1.8]), <= high school degree (1.6[1.5-1.8]), dyspnea (2.3[2.1-2.6]), difficulty walking (2.8[2.5-3.2]), and co-morbid diabetes (1.2[1.1-1.4]), arthritis (1.3[1.2-1.5]) or cancer (1.2[1.1-1.4]). CONCLUSIONS: Depressive symptoms are common in COPD and are more likely to occur in COPD than in other common chronic illnesses. The risk factors identified may be used for targeted depression screening in COPD patients. C1 [Schane, Rebecca E.; Woodruff, Prescott G.] Univ Calif San Francisco, Dept Med, Div Pulm Crit Care Med, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Covinsky, Ken E.; Walter, Louise C.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Schane, Rebecca E.; Dinno, Alexis] Univ Calif San Francisco, Dept Med, Ctr Tobacco Control Res & Educ, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Schane, RE (reprint author), Univ Calif San Francisco, Dept Med, Div Pulm Crit Care Med, Cardiovasc Res Inst, 530 Parnassus Ave,Suite 366, San Francisco, CA 94143 USA. EM rschane@medsfgh.ucsf.edu FU NIH [T32 HL007185, HL074431, 1 R25 CA113710-02]; National Institute on Aging [R01AG023626] FX Dr. Dinno is a recipient of an NIH Training Grant 1 R25 CA113710-02. NR 45 TC 53 Z9 56 U1 1 U2 4 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 NOV PY 2008 VL 23 IS 11 BP 1757 EP 1762 DI 10.1007/s11606-008-0749-z PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 379VI UT WOS:000261423900005 PM 18690488 ER PT J AU Lu-Yao, G Albertsen, PC Stanford, JL Stukel, TA Walker-Corkery, E Barry, MJ AF Lu-Yao, Grace Albertsen, Peter C. Stanford, Janet L. Stukel, Therese A. Walker-Corkery, Elizabeth Barry, Michael J. TI Screening, Treatment, and Prostate Cancer Mortality in the Seattle Area and Connecticut: Fifteen-year Follow-up SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE prostate cancer; cancer screening; men's health; outcomes; practice variation ID UNITED-STATES; INTERPRETING TRENDS; SURVEILLANCE SERIES; REGRESSION; IMPACT; RATES; DEATH AB BACKGROUND: Prior to introduction of the prostate-specific antigen (PSA) test, the Seattle-Puget Sound and Connecticut Surveillance, Epidemiology and End Results (SEER) areas had similar prostate cancer mortality rates. Early in the PSA era (1987-1990), men in the Seattle area were screened and treated more intensively for prostate cancer than men in Connecticut. OBJECTIVE: We previously reported more intensive screening and treatment early in the PSA era did not lower prostate cancer mortality through 11 years and now extend follow-up to 15 years. DESIGN: Natural experiment comparing two fixed population-based cohorts. SUBJECTS: Male Medicare beneficiaries ages 65-79 from the Seattle (N = 94,900) and Connecticut (N = 120,621) SEER areas, followed from 1987-2001. MEASUREMENTS: Rates of prostate cancer screening; treatment with radical prostatectomy, external beam radiotherapy, and androgen deprivation therapy; and prostate cancer-specific mortality. MAIN RESULTS: The 15-year cumulative incidences of radical prostatectomy and radiotherapy through 2001 were 2.84% and 6.02%, respectively, for Seattle cohort members, compared to 0.56% and 5.07% for Connecticut cohort members (odds ratio 5.20, 95% confidence interval 3.22 to 8.42 for surgery and odds ratio 1.24, 95% confidence interval 0.98 to 1.58 for radiation). The cumulative incidence of androgen deprivation therapy from 1991-2001 was 4.78% for Seattle compared to 6.13% for Connecticut (odds ratio 0.77, 95% confidence interval 0.67 to 0.87). The adjusted rate ratio of prostate cancer mortality through 2001 was 1.02 (95% C.I. 0.96 to 1.09) in Seattle versus Connecticut. CONCLUSION: Among men aged 65 or older, more intensive prostate cancer screening early in the PSA era and more intensive treatment particularly with radical prostatectomy over 15 years of follow-up were not associated with lower prostate cancer-specific mortality. C1 [Walker-Corkery, Elizabeth; Barry, Michael J.] Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. [Lu-Yao, Grace] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Albertsen, Peter C.] Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Programs Epidemiol & Prostate Canc, Seattle, WA 98104 USA. [Stukel, Therese A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, 50 Stanford St,9th Floor, Boston, MA 02114 USA. EM mbarry@partners.org FU Agency for Health Care Research and Quality [HS 08397, HS 10278] FX This research was funded by grants from the Agency for Health Care Research and Quality (HS 08397, HS 10278). NR 21 TC 28 Z9 29 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2008 VL 23 IS 11 BP 1809 EP 1814 DI 10.1007/s11606-008-0785-8 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 379VI UT WOS:000261423900013 PM 18795372 ER PT J AU Sudore, RL Landefeld, CS Pantilat, SZ Noyes, KM Schillinger, D AF Sudore, Rebecca L. Landefeld, C. Seth Pantilat, Steven Z. Noyes, Kathryn M. Schillinger, Dean TI Reach and Impact of a Mass Media Event Among Vulnerable Patients: The Terri Schiavo Story SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE mass media; public health; advance care planning; health literacy; vulnerable populations ID HEALTH-CARE; NEWS MEDIA; LITERACY; LIFE; COMMUNICATION; COVERAGE; CANCER; ADULTS; TRIAL; END AB BACKGROUND: It is unknown whether health-related media stories reach diverse older adults and influence advance care planning (ACP). OBJECTIVE: To determine exposure to media coverage of Terri Schiavo (TS) and its impact on ACP. DESIGN AND PARTICIPANTS: Descriptive study of 117 English/Spanish-speakers, aged >= 50 years (mean 61 years) from a county hospital, interviewed six months after enrollment into an advance directive study. MEASUREMENTS: We assessed whether participants had heard of TS and subject characteristics associated with exposure. We also asked whether, because of TS, subjects engaged in ACP. MAIN RESULTS: Ninety-two percent reported hearing of TS. Participants with adequate literacy were more likely than those with limited literacy to report hearing of TS (100% vs. 79%, P<.001), as were participants with >= a high school vs. < high school education (97% vs. 82%, P=.004), and English vs. Spanish-speakers (96% vs. 85%, P=.04). Because of TS, many reported clarifying their own goals of care (61%), talking to their family/friends about ACP (66%), and wanting to complete an advance directive (37%). CONCLUSIONS: Most diverse older adults had heard of TS and reported that her story activated them to engage in ACP. Media stories may provide a powerful opportunity to engage patients in ACP and develop public health campaigns. C1 [Sudore, Rebecca L.; Landefeld, C. Seth; Noyes, Kathryn M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Sudore, Rebecca L.; Landefeld, C. Seth; Noyes, Kathryn M.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Sudore, Rebecca L.; Landefeld, C. Seth; Pantilat, Steven Z.; Schillinger, Dean] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Schillinger, Dean] San Francisco Gen Hosp, UCSF Ctr Vulnerable Populat, San Francisco, CA 94110 USA. RP Sudore, RL (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM rsucsf@yahoo.com FU NCRR NIH HHS [UL1 RR024131]; NIA NIH HHS [K-23 AG030344-01, 5R01AG023626-02, R01 AG023626, AG000212, K07 AG000912, K23 AG030344, T32 AG000212] NR 19 TC 10 Z9 11 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2008 VL 23 IS 11 BP 1854 EP 1857 DI 10.1007/s11606-008-0733-7 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 379VI UT WOS:000261423900020 PM 18716849 ER PT J AU Joseph, J Joseph, L Devi, S Kennedy, RH AF Joseph, Jacob Joseph, Lija Devi, Sulochana Kennedy, Richard H. TI Effect of Anti-oxidant Treatment on Hyperhomocysteinemia-induced Myocardial Fibrosis and Diastolic Dysfunction SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID NORMOTENSIVE RATS; HYPERTENSIVE-RATS; HEART-FAILURE; HYPERTROPHY; HOMOCYSTEINE; INFARCTION; LEADS AB Background: Recent studies demonstrate that hyerhomocysteinemia is a risk factor for heart failure. Oxidant stress is a major mediator of the pathogenic effects of hyperhomocysteinemia. Methods: We utilized a rat model of diet-induced hyperhomocysteinemia to examine whether treatment with an anti-oxidant vitamin (C&E) combination will prevent hyperhomocysteinemia-induced myocardial fibrosis. Results: Dietary anti-oxidant therapy attenuated hyperhomocysteinemia-induced increases in myocardial oxidant stress and myocardial fibrosis, and diastolic dysfunction. Conclusions: Hyperhomocysteinemia acts via oxidant stress to promote myocardial fibrosis and dysfunction. Dietary anti-oxidant therapy Could be an important preventive and therapeutic strategy in diastolic heart failure. J Heart Lung Transplant 2008-127:1237-41. Published by Elsevier Inc. on behalf of the International Society for Heart and Lung Transplantation. C1 [Joseph, Jacob] VA Boston Healthcare Syst, Dept Med, Cardiol Sect 111, W Roxbury, MA 02132 USA. [Joseph, Jacob; Devi, Sulochana] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Joseph, Lija] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Kennedy, Richard H.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Dept Med, Cardiol Sect 111, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM jacob.joseph@bmc.org FU American Heart Association FX The work described was supported in part by a Beginning Grant-In-Aid from the American Heart Association to Dr Joseph. NR 13 TC 18 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2008 VL 27 IS 11 BP 1237 EP 1241 DI 10.1016/j.healun.2008.07.024 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 369AE UT WOS:000260664100008 PM 18971097 ER PT J AU Lago, RM Pencina, MJ Wang, TJ Lanier, KJ D'Agostino, RB Kannel, WB Vasan, RS AF Lago, Rodrigo M. Pencina, Michael J. Wang, Thomas J. Lanier, Katherine J. D'Agostino, Ralph B. Kannel, William B. Vasan, Ramachandran S. TI Interindividual variation in serum sodium and longitudinal blood pressure tracking in the Framingham Heart Study SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; epidemiology; hypertension; longitudinal cstudies; metabolism; serum sodium ID ESSENTIAL-HYPERTENSION; PLASMA SODIUM; POTASSIUM; ALDOSTERONE; DISEASE AB Background Recent cross-sectional studies have suggested that higher serum sodium levels may be a marker of elevated blood pressure. It is unclear whether serum sodium levels are related to the risk of developing hypertension in the community. Methods We investigated the association of serum sodium with longitudinal blood pressure tracking and incidence of hypertension in 2172 nonhypertensive Framingham Offspring Study participants (mean age 42 years, 54% women). We defined an increase in blood pressure as an increment of at least one category (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure), and incident hypertension as a systolic blood pressure of at least 140 or a diastolic blood pressure of at least 90mmHg, or use of antihypertensive medications. Serum sodium was analyzed as a continuous variable, and as categories. Results Cross-sectionally, serum sodium was not associated with systolic or diastolic blood pressure (P exceeded 0.10). On follow-up (mean 4.4 years), 805 participants (37%, 418 women) progressed by at least one blood pressure category, and 318 (15%, 155 women) developed new-onset hypertension. In multivariable logistic regression analyses (adjusting for age, sex, baseline blood pressure, diabetes, BMI, weight gain and smoking), progression (odds ratio per SD increment 0.93, 95% confidence interval 0.85-1.03), or with hypertension incidence (odds ratio per SD increment 0.94, 95% confidence interval 0.82-1.08). Conclusion In our large community-based sample, serum sodium was not associated with blood pressure cross-sectionally, or with blood pressure tracking or hypertension incidence longitudinally. J Hypertens 26: 2121-2125 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Lago, Rodrigo M.; Pencina, Michael J.; Wang, Thomas J.; Lanier, Katherine J.; D'Agostino, Ralph B.; Kannel, William B.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Cardiol, Boston, MA USA. [Pencina, Michael J.; Lanier, Katherine J.; D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Prevent Med Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU National Institute of Health and National Heart, Lung, and Blood Institute [NO1-HC-25195, K23HL074077, 2K24HL04334] FX Supported by National Institute of Health and National Heart, Lung, and Blood Institute, contract NO1-HC-25195, K23HL074077 (T.J.W.), and 2K24HL04334 (R.S.V.). NR 20 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD NOV PY 2008 VL 26 IS 11 BP 2121 EP 2125 DI 10.1097/HJH.0b013e32830fe4a5 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367RP UT WOS:000260570300009 PM 18854750 ER PT J AU Yerly, D Heckerman, D Allen, T Suscovich, TJ Jojic, N Kadie, C Pichler, WJ Cerny, A Brander, C AF Yerly, Daniel Heckerman, David Allen, Todd Suscovich, Todd J. Jojic, Nebojsa Kadie, Carl Pichler, Werner J. Cerny, Andreas Brander, Christian TI Design, Expression, and Processing of Epitomized Hepatitis C Virus-Encoded CTL Epitopes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; HLA CLASS-I; IMMUNE-RESPONSES; HIV; INFECTION; SEQUENCES; RECOGNITION; DIVERSITY; EVOLUTION AB Hepatitis C virus (HCV) vaccine efficacy may crucially depend on immunogen length and coverage of viral sequence diversity. However, covering a considerable proportion of the circulating viral sequence variants would likely require long immunogens, which for the conserved portions of the viral genome, would contain unnecessarily redundant sequence information. In this study, we present the design and in vitro performance analysis of a novel "epitome" approach that compresses frequent immune targets of the cellular immune response against HCV into a shorter immunogen sequence. Compression of immunological information is achieved by partial overlapping shared sequence motifs between individual epitopes. At the same time, sequence diversity coverage is provided by taking advantage of emerging cross-reactivity patterns among epitope variants so that epitope variants associated with the broadest variant cross-recognition are preferentially included. The processing and presentation analysis of specific epitopes included in such a compressed, in vitro-expressed HCV epitome indicated effective processing of a majority of tested epitopes, although re-presentation of some epitopes may require refined sequence design. Together, the present study establishes the epitome approach as a potential powerful tool for vaccine immunogen design, especially suitable for the induction of cellular immune responses against highly variable pathogens. The Journal of Immunology, 2008, 181: 6361-6370. C1 [Brander, Christian] Hosp Univ Germans Trias & Pujol, Fdn IrsiCaixa, Lab Retrovirol, Barcelona 08916, Catalonia, Spain. [Yerly, Daniel; Pichler, Werner J.] Univ Bern, Clin Rheumatol & Clin Immunol, Bern, Switzerland. [Yerly, Daniel; Allen, Todd; Suscovich, Todd J.; Brander, Christian] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Yerly, Daniel; Allen, Todd; Suscovich, Todd J.; Brander, Christian] Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA 02129 USA. [Heckerman, David; Jojic, Nebojsa; Kadie, Carl] Microsoft Res, Redmond, WA 98052 USA. [Cerny, Andreas] Osped Reg Lugano, Dept Med, Lugano, Switzerland. [Brander, Christian] ICREA, Barcelona, Spain. [Brander, Christian] Irsicaixa Fdn, Badalona, Spain. RP Brander, C (reprint author), Hosp Univ Germans Trias & Pujol, Fdn IrsiCaixa, Lab Retrovirol, Ctra Canyet S-N, Barcelona 08916, Catalonia, Spain. EM cbrander@irsicaixa.es RI Allen, Todd/F-5473-2011 FU Swiss National Science Foundation [3200B0-103874]; European Community (European Community Network VIRGIL) FX This work was supported by grants from the Swiss National Science Foundation (Grant 3200B0-103874) and the European Community (European Community Network VIRGIL). NR 37 TC 14 Z9 15 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2008 VL 181 IS 9 BP 6361 EP 6370 PG 10 WC Immunology SC Immunology GA 368YI UT WOS:000260659000062 PM 18941227 ER PT J AU Butler, MO Friedlander, PA Mooney, M Berezovskaya, A Drury, L Flavin, M Murray, A Imataki, O Tanaka, M Daley, H Armant, M Kao, G Hodi, FS Nadler, LM Hirano, N AF Butler, Marcus O. Friedlander, Philip A. Mooney, Mary Berezovskaya, Alla Drury, Linda Flavin, Marisa Murray, Andrew Imataki, Osamu Tanaka, Makito Daley, Heather Armant, Myriam Kao, Grace Hodi, Frank Stephen Nadler, Lee M. Hirano, Naoto TI Adoptive Transfer of "Young" MART1/Melan-A CTL Generated With Artificial APC and IL-2/IL-15: Emergence and Persistence of a Memory/Effector Phenotype SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Butler, Marcus O.; Friedlander, Philip A.; Mooney, Mary; Berezovskaya, Alla; Drury, Linda; Flavin, Marisa; Murray, Andrew; Imataki, Osamu; Tanaka, Makito; Daley, Heather; Armant, Myriam; Kao, Grace; Hodi, Frank Stephen; Nadler, Lee M.; Hirano, Naoto] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 921 EP 922 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800016 ER PT J AU Rodriguez, PC Ernstoff, MS Hernandez, CP Atkins, M Zabaleta, J Sierra, RA Ochoa, AC AF Rodriguez, Paido C. Ernstoff, Marc S. Hernandez, Claudia P. Atkins, Michael Zabaleta, Jovanny Sierra, Rosa A. Ochoa, Augusto C. TI Arginase I Producing Myeloid Derived Suppressor Cells (MDSC) in Renal Cell Carcinoma are a Sub Population of Activated Granulocytes SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Rodriguez, Paido C.; Hernandez, Claudia P.; Zabaleta, Jovanny; Sierra, Rosa A.; Ochoa, Augusto C.] Louisiana State Univ, New Orleans, LA USA. [Ernstoff, Marc S.] Dartmouth Med Sch, Dept Med, Lebanon, NH USA. [Atkins, Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Atkins, Michael] Harvard Univ, Dana Farber Harvard Canc Ctr, Renal Canc Program, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 931 EP 931 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800047 ER PT J AU Smith, RA Blois, J Yuan, H Aikawa, E Ellson, C Figueiredo, JL Weissleder, R Cantley, L Josephson, L AF Smith, Ralph A. Blois, Joe Yuan, Hushan Aikawa, Elena Ellson, Christopher Figueiredo, Jose-Luiz Weissleder, Ralph Cantley, Lewis Josephson, Lee TI The Antiproliferative Cytostatic Effects of a Self-activating Viridin Prodrug SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Smith, Ralph A.; Blois, Joe; Yuan, Hushan; Aikawa, Elena; Figueiredo, Jose-Luiz; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Cantley, Lewis] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02138 USA. [Ellson, Christopher] MIT, Dept Biol, Cambridge, MA USA. [Cantley, Lewis] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 931 EP 932 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800049 ER PT J AU Logan, T Hodi, FS Margolin, K McDermott, DF Ernstoff, MS Kirkwood, JM Oza, A Pujade-Lauraine, E Lhomme, C Rolland, F Medioni, J Houede, N Tsuchihashi, Z Hu, B Wu, D Patti-Diaz, L Lang, L Huang, S Platero, JS Shah, A Wojtaszek, C Goldberg, S Feltquate, D Sznol, M AF Logan, T. Hodi, F. S. Margolin, K. McDermott, D. F. Ernstoff, M. S. Kirkwood, J. M. Oza, A. Pujade-Lauraine, E. Lhomme, C. Rolland, F. Medioni, J. Houede, N. Tsuchihashi, Z. Hu, B. Wu, D. Patti-Diaz, L. Lang, L. Huang, S. Platero, J. S. Shah, A. Wojtaszek, C. Goldberg, S. Feltquate, D. Sznol, M. TI Phase I Study of BMS-663513, a Fully Human Anti-CD137 Agonist Monoclonal Antibody, in Patients (Pts) With Advanced Cancer (CA) SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Logan, T.] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Margolin, K.] City Hope Natl Med Ctr, Los Angeles, CA USA. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ernstoff, M. S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Kirkwood, J. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Oza, A.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Pujade-Lauraine, E.] Hop Hotel Dieu, F-75181 Paris, France. [Lhomme, C.] Inst Gustave Roussy, Villejuif, France. [Medioni, J.] Hop Europeen Pompidou, Paris, France. [Houede, N.] Inst Bergonie, Bordeaux, France. [Huang, S.; Platero, J. S.; Shah, A.; Wojtaszek, C.; Goldberg, S.; Feltquate, D.] Bristol Myers Squibb Co, Princeton, NJ USA. [Sznol, M.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 956 EP 956 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800127 ER PT J AU Libermann, TA Bhasin, M Joseph, MG Signoretti, S Ernstoff, MS McDermott, DF Atkins, MB AF Libermann, Towia A. Bhasin, Manoj Joseph, Marie G. Signoretti, Sabina Ernstoff, Marc S. McDermott, David F. Atkins, Michael B. TI Gene Expression Profiling Signatures Associated With RCC Response to IL-2 Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Libermann, Towia A.; Bhasin, Manoj; Joseph, Marie G.] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Libermann, Towia A.; Bhasin, Manoj; Signoretti, Sabina; McDermott, David F.; Atkins, Michael B.] Kidney Canc Program, Boston, MA USA. [Libermann, Towia A.; Bhasin, Manoj; Joseph, Marie G.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ernstoff, Marc S.] Dartmouth Hitchcock Med Ctr, Div Hematol Oncol, Lebanon, NH 03766 USA. [McDermott, David F.; Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 958 EP 958 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800134 ER PT J AU Osawa, M Fisher, DE AF Osawa, Masatake Fisher, David E. TI Notch and Melanocytes: Diverse Outcomes from a Single Signal SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID PRIMARY MELANOMA PROGRESSION AB Notch signaling is an evolutionally conserved pathway that serves as a critical regulator of cell fate. From a series of studies, including a report in this issue, researchers have begun to elucidate the critical functions of notch signaling in the regulation of melanocyte lineage development. With evidence of a recently identified role for notch signaling in melanomagenesis, characterization of downstream molecular events may offer potential avenues for the development of novel therapeutic strategies. C1 [Osawa, Masatake; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Osawa, Masatake; Fisher, David E.] Harvard Univ, Sch Med, Charlestown, MA USA. [Fisher, David E.] Massachusetts Gen Hosp, Dept Med Oncol, Melanoma Program, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Their 204,55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org NR 17 TC 14 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2008 VL 128 IS 11 BP 2571 EP 2574 DI 10.1038/jid.2008.289 PG 5 WC Dermatology SC Dermatology GA 364XL UT WOS:000260368800004 PM 18927539 ER PT J AU Hocker, TL Singh, MK Tsao, H AF Hocker, Thomas L. Singh, Meena K. Tsao, Hensin TI Melanoma Genetics and Therapeutic Approaches in the 21st Century: Moving from the Benchside to the Bedside SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Review ID C-KIT EXPRESSION; FACTOR-KAPPA-B; CHEMOTHERAPY-INDUCED APOPTOSIS; CHEMOSENSITIZES HUMAN-MELANOMA; METASTATIC MALIGNANT-MELANOMA; CONGENITAL MELANOCYTIC NEVI; PROTEASOME INHIBITOR PS-341; TUMOR-SUPPRESSOR GENE; BCL-2 FAMILY-MEMBERS; PHASE-II TRIAL AB Metastatic melanoma is notoriously one of the most difficult cancers to treat. Although many therapeutic regimens have been tested, very few achieve response rates greater than 25%. Given the rising incidence of melanoma and the paucity of effective treatments, there is much hope and excitement in leveraging recent genetic and molecular insights for therapeutic advantage. Over the past 30 years, elegant studies by many groups have helped decipher the complex genetic networks involved in melanoma proliferation, progression and survival, as well as several genes involved in melanocyte development and survival. Many of these oncogenic loci and pathways have become crucial targets for pharmacological development. In this article we review: (1) our current understanding of melanoma genetics within the context of signaling networks; (2) targeted therapies, including an extensive discussion of promising agents that act in the Bcl-2 signaling network; (3) future areas of research. C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hocker, Thomas L.; Singh, Meena K.; Tsao, Hensin] Harvard Univ, Sch Med, Boston, MA USA. [Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org FU American Cancer Society FX This work was partly supported by a grant from the American Cancer Society (to HT) and generous donors to the MGH. NR 204 TC 97 Z9 99 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2008 VL 128 IS 11 BP 2575 EP 2595 DI 10.1038/jid.2008.226 PG 21 WC Dermatology SC Dermatology GA 364XL UT WOS:000260368800005 PM 18927540 ER PT J AU Meeran, SM Punathil, T Katiyar, SK AF Meeran, Syed M. Punathil, Thejass Katiyar, Santosh K. TI IL-12 Deficiency Exacerbates Inflammatory Responses in UV-Irradiated Skin and Skin Tumors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; IFN-GAMMA PRODUCTION; GREEN TEA; INTERLEUKIN-12-DEFICIENT MICE; ULTRAVIOLET-RADIATION; COX-2 EXPRESSION; DNA-REPAIR; T-CELL; INHIBITION; CANCER AB IL-12 deficiency has been shown to promote photocarcinogenesis in mice. As UVB-induced inflammation is an important tumor-promoting event in the development of skin tumors, we determined the effects of IL-12-deficiency on UVB-induced inflammatory responses in mice. For this purpose, IL-12-knockout (IL-12 KO) and their wild-type counterparts were subjected to a photocarcinogenesis protocol; skin and tumor samples were collected at the termination of the experiment, and analyzed for biomarkers of inflammation and their mediators. We found that the levels of infiltrating leukocytes, myeloperoxidase, proliferating cell-nuclear antigen (PCNA), COX-2, PGE(2), and the proinflammatory cytokines IL-1 beta, TNF-alpha, and IL-6 were higher in the UVB-exposed skin of IL-12 KO than in that of wild-type mice. In a short-term experiment, pretreatment of IL-12 KO mice with rIL-12 (50 ng per mouse) before each exposure to UVB increased the repair rate of UVB-induced cyclobutane pyrimidine dimers, while inhibiting UVB-induced increases in myeloperoxidase, COX-2, PGE2, PCNA, TNF-alpha, and IL-1 beta in the skin as compared with non-rIL-12-treated IL-12 KO mice. Similarly, tumors of IL-12 KO mice expressed higher levels of inflammatory responses than those of wild-type mice. Together, our data suggest that IL-12 KO mice are more susceptible to both UVB-induced inflammation and photocarcinogenesis because of the deficiency in the repair of UVB-induced DNA damage. C1 [Meeran, Syed M.; Punathil, Thejass; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Center for Complementary and Alternative Medicine, NCCAM/NIH [1 RO1 AT002536]; Veterans Affairs Merit Review Award FX This work was supported by funds from the National Center for Complementary and Alternative Medicine, NCCAM/NIH (1 RO1 AT002536; SKK), and Veterans Affairs Merit Review Award (SKK). NR 36 TC 35 Z9 38 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2008 VL 128 IS 11 BP 2716 EP 2727 DI 10.1038/jid.2008.140 PG 12 WC Dermatology SC Dermatology GA 364XL UT WOS:000260368800019 PM 18509359 ER PT J AU Busaba, NY Sin, HJ Salman, SD AF Busaba, N. Y. Sin, H-J Salman, S. D. TI Impact of gender on clinical presentation of chronic rhinosinusitis with and without polyposis SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE Sinusitis; Nasal Polyps; Sex Factors ID QUALITY-OF-LIFE; CHRONIC SINUSITIS; HEADACHE; SYMPTOMS; MIGRAINE AB Study objective: To determine the impact of a patient's gender on the clinical presentation of chronic rhinosinusitis with and without nasal polyposis. Study design and methods: Prospective study of 514 adult patients who presented with chronic rhinosinusitis with and without nasal polyposis. The patients were divided into two groups based on gender: female (n = 273) and male (n = 241). The following data were collected: presenting symptoms, co-morbidities, nasal endoscopy and sinus computed tomography findings, diagnosis, and outcome of surgery. Statistical analysis was performed using the chi-square test, with statistical significance set at p < 0.05. Results: Facial pain and headache were more prevalent among women, while nasal obstruction was more prevalent among men (p < 0.05). There was no statistically significant difference in the prevalence of environmental allergy, asthma, psychiatric illness or anatomical variants obstructing the osteomeatal unit, comparing the genders. Chronic rhinosinusitis without polyposis was the more common diagnosis among women, while chronic rhinosinusitis with polyposis was the more common diagnosis among men (p < 0.05). Following surgery, a higher percentage of male patients reported improvement in nasal obstruction (p < 0.05), but there was no statistically significant difference in the improvement of the other presenting symptoms, comparing the genders. Conclusion: Women who suffer from chronic rhinosinusitis are more likely to complain of facial pain or headache on presentation and to be diagnosed with chronic rhinosinusitis without polyposis. On the other hand, men are more likely to complain of nasal obstruction, to be diagnosed C1 [Busaba, N. Y.; Sin, H-J; Salman, S. D.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Busaba, N. Y.] VA Boston HealthCare Syst, Div Otolaryngol, Boston, MA USA. [Busaba, N. Y.; Sin, H-J; Salman, S. D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM nicolas_busaba@meei.harvard.edu NR 11 TC 8 Z9 8 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD NOV PY 2008 VL 122 IS 11 BP 1180 EP 1184 DI 10.1017/S0022215107001302 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 377LH UT WOS:000261252200008 PM 18184447 ER PT J AU Hathaway, JE Zimmer, B Willis, G Silverman, JG AF Hathaway, Jeanne E. Zimmer, Bonnie Willis, Georgianna Silverman, Jay G. TI Perceived Changes in Health and Safety Following Participation in a Health Care-Based Domestic Violence Program SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Article DE intimate partner violence; outcome and process assessment (health care); program evaluation; spouse abuse (counseling) ID INTIMATE PARTNER VIOLENCE; BATTERED WOMEN; PREGNANT-WOMEN; ADVOCACY PROGRAM; ABUSIVE PARTNERS; BIRTH-WEIGHT; INTERVENTION; VICTIMIZATION; SERVICES; CHILDREN AB This descriptive study explores perceived changes in health and safety and the potential process by which these changes occur. Forty-nine women experiencing intimate partner abuse participated in a health care-based domestic violence (DV) advocacy program for 6 months or more. An analysis of structured interviews in English and Spanish found that the majority of participants perceived positive changes in their personal safety and emotional health because of their involvement in the program. Some participants also perceived improvements in their physical health, unhealthy coping behaviors (e.g., overeating and smoking). and health care following program involvement. Participants' responses suggest a process of change whereby DV advocacy services first contribute to improved safety and emotional health, which then facilitates behavioral changes. Behavioral changes may subsequently contribute to improvements in physical health, which may also benefit emotional health. Longitudinal evaluations are needed to evaluate the impact of DV advocacy and other interventions for partner abuse on women's health and safety over time. J Midwifery Womens Health 2008;53:547-555 (C) 2008 by the American College of Nurse-Midwives. C1 [Hathaway, Jeanne E.; Silverman, Jay G.] Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Violence Prevent Programs, Boston, MA 02115 USA. [Zimmer, Bonnie] Massachusetts Gen Hosp, HAVEN Program, Boston, MA 02114 USA. [Willis, Georgianna] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02115 USA. [Silverman, Jay G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Hathaway, JE (reprint author), Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Violence Prevent Programs, 677 Huntington Ave,Landmark Ctr,3 East, Boston, MA 02115 USA. EM jhathawa@hsph.harvard.edu FU Massachusetts General Hospital/Partners Community Benefits Program in Boston, MA; Massachusetts General Hospital Social Service Department FX This study was funded by the Massachusetts General Hospital/Partners Community Benefits Program in Boston, MA. The Massachusetts General Hospital Social Service Department provided additional support for the completion of this manuscript. The authors are extremely grateful to the HAVEN participants who shared their experiences with us so that this information could help others facing abuse by an intimate partner. We also thank the HAVEN advocates for their assistance with this study while attending to the primary needs of program participants, as well as Arlene Burns, Ellie MacDonald, and Danelle Marable for assistance with data entry and analysis. NR 45 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD NOV-DEC PY 2008 VL 53 IS 6 SI SI BP 547 EP 555 DI 10.1016/j.jmwh.2008.07.008 PG 9 WC Nursing SC Nursing GA 369XU UT WOS:000260728000009 PM 18984511 ER PT J AU Ogino, S Nosho, K Kawasaki, T Zepf, D Yan, L Longtine, JA Fuchs, C AF Ogino, S. Nosho, K. Kawasaki, T. Zepf, D. Yan, L. Longtine, J. A. Fuchs, C. TI PIK3CA Mutation in Colorectal Cancer Detected by Pyrosequencing: Relationship with Genetic and Epigenetic Alterations SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT 14th Annual Meeting of the Association-for-Molecular-Pathology CY OCT 29-NOV 02, 2008 CL Grapevine, TX SP Assoc Mol Pathol C1 [Ogino, S.; Zepf, D.; Longtine, J. A.; Fuchs, C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Nosho, K.; Kawasaki, T.] Dana Farber Canc Inst, Boston, MO USA. [Yan, L.] EpigenDx, Foxboro, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2008 VL 10 IS 6 BP 601 EP 601 PG 1 WC Pathology SC Pathology GA 367DV UT WOS:000260533600175 ER PT J AU Reddy, V Li, Y Lerner, E AF Reddy, Vemuri B. Li, Yhong Lerner, Ethan A. TI Maxadilan, the PAC1 Receptor, and Leishmaniasis SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT DE Maxadilan; Sand fly; Leishmaniasis ID FLY LUTZOMYIA-LONGIPALPIS; POTENT VASODILATORY PEPTIDE; SALIVARY PROTEIN; VASORELAXANT; INFECTION; GLANDS; VECTOR; BRAIN; CELLS AB Maxadilan is a vasodilator peptide isolated from sand fly salivary glands. The vasodilator effects of maxadilan are mediated by the PAC1 receptor, although maxadilan and PACAP do not share sequence homology. Sand flies are the vector of the parasitic disease leishmaniasis. The peptide aids the sand fly in obtaining a blood meal while enhancing the infectivity of leishmania parasites transmitted by this arthropod vector. Aspects of maxadilan, PAC1, and leishmaniasis are discussed. C1 [Reddy, Vemuri B.; Li, Yhong; Lerner, Ethan A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Chareleston, MA 02129 USA. RP Lerner, E (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Bldg 149,13th St, Chareleston, MA 02129 USA. EM elerner@partners.org NR 26 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2008 VL 36 IS 1-3 BP 241 EP 244 DI 10.1007/s12031-008-9079-1 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 376JP UT WOS:000261180200027 PM 18509762 ER PT J AU Maloney, KN Fujita, M Eggert, US Schroeder, FC Field, CM Mitchison, TJ Clardy, J AF Maloney, Katherine N. Fujita, Masaki Eggert, Ulrike S. Schroeder, Frank C. Field, Christine M. Mitchison, Timothy J. Clardy, Jon TI Actin-Aggregating Cucurbitacins from Physocarpus capitatus SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ANTICANCER AGENTS; INHIBITORS; CYTOSKELETON; TARGETS AB Bioassay-guided fractionation of Physocarpus capitatus yielded two new cucurbitacins (3 and 4) along with the known cucurbitacin F (1) and dihydrocucurbitacin F (2). Preliminary mechanism of action studies indicate that the cucurbitacins cause actin aggregates and inhibit cell division. C1 [Maloney, Katherine N.; Fujita, Masaki; Eggert, Ulrike S.; Schroeder, Frank C.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Field, Christine M.; Mitchison, Timothy J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Eggert, Ulrike S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Clardy, J (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM jon_clardy@hms.harvard.edu RI Fujita, Masaki/A-8464-2012; Schroeder, Frank/H-5026-2012; OI Schroeder, Frank/0000-0002-4420-0237 FU NIH [CA24487, R01 GM023928-25]; NSF; Natural Products Branch of the National Cancer Institute [NPID N102479] FX This research was supported by NIH grant CA24487 (J.C.). K.N.M. was supported by an NSF Graduate Research Fellowship. HRESIMS was performed by S. Mullen of the Mass Spectrometry Facility at the University of Illinois at Urbana-Champaign. U.S.E. was a Merck-sponsored fellow of the Helen Hay Whitney Foundation. U.S.E., C.M.F., and T.J.M. were supported by NIH grant R01 GM023928-25 awarded to T.J.M. The organic extract of P. capitatus (NPID N102479) was provided by G. Cragg in the Natural Products Branch of the National Cancer Institute. NR 14 TC 19 Z9 19 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2008 VL 71 IS 11 BP 1927 EP 1929 DI 10.1021/np8005259 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 378PG UT WOS:000261335800027 PM 18959442 ER PT J AU Surman, CBH AF Surman, Craig B. H. TI ADHD In Adults: What the Science Says SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 [Surman, Craig B. H.] Massachusetts Gen Hosp, Res Program, Cambridge, MA USA. RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Res Program, Cambridge, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 2008 VL 196 IS 11 BP 857 EP 858 DI 10.1097/NMD.0b013e31818b466b PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 372SK UT WOS:000260921900013 ER PT J AU Musunuru, K Kesari, S AF Musunuru, Kiran Kesari, Santosh TI Paraneoplastic opsoclonus-myoclonus ataxia associated with non-small-cell lung carcinoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE paraneoplastic opsoclonus-myoclonus ataxia; non-small cell lung cancer; anti-Ri antibody ID RNA-BINDING PROTEIN; ANTI-RI ANTIBODIES; DEGENERATION; PATIENT; DISEASE; SYSTEM AB We report a case of the paraneoplastic opsoclonus-myoclonus ataxia syndrome in a patient with non-small cell lung carcinoma, which represents a highly unusual association. The patient simultaneously manifested both severe neurologic symptoms and widely metastatic disease, complicating her treatment. C1 [Kesari, Santosh] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Musunuru, Kiran] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kesari, Santosh] Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Boston, MA 02115 USA. [Kesari, Santosh] Harvard Univ, Sch Med, Boston, MA USA. RP Kesari, S (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, SW 460,44 Binney St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 FU NHLBI NIH HHS [T32 HL007208, T32 HL007208-31] NR 11 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD NOV PY 2008 VL 90 IS 2 BP 213 EP 216 DI 10.1007/s11060-008-9650-1 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 354XB UT WOS:000259672100011 PM 18618225 ER PT J AU Fitten, LJ Ortiz, F Fairbanks, L Rosenthal, M Cole, GN Nourhashemi, F Sanchez, MA AF Fitten, L. J. Ortiz, F. Fairbanks, L. Rosenthal, M. Cole, G. N. Nourhashemi, F. Sanchez, M. A. TI DEPRESSION, DIABETES AND METABOLIC-NUTRITIONAL FACTORS IN ELDERLY HISPANICS SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE Depression; metabolic-nutritional factors; elderly hispanics; sea fish ID 3RD NATIONAL-HEALTH; POLYUNSATURATED FATTY-ACIDS; OLDER MEXICAN-AMERICANS; COGNITIVE IMPAIRMENT; BIPOLAR DEPRESSION; US ADULTS; SYMPTOMS; RISK; OMEGA-3-FATTY-ACIDS; POPULATION AB Objective: To examine the relationship of depression to metabolic and nutritional risk factors in older Hispanics. Design: Crossectional study. Setting: Subjects were part of a community-based, cognitive evaluation project that examined 301 subjects in the Eastern San Fernando Valley of Southern California. Participants: Two elderly Hispanic groups: 53 clinically depressed, with memory complaints but not demented subjects, and 33 generally healthy, cognitively asymptomatic subjects. Measurements: The results of functional and nutritional questionnaires, a medical and neurological examination, 12-hour fasting clinical laboratory tests, MRI or CT scans, and neuropsychological testing. Results: Both groups were nearly identical along socio-demographic variables. However, the depressed group differed significantly from the general healthy group not only in percent of diabetics (38% vs. 18%), but in the amount of poorly controlled diabetes, and the depressed group consumed about half the amount of fish that the generally healthy group did. Conclusions: This study suggests that factors such as poorly controlled diabetes combined with low consumption of foods high in omega-3 fatty acid content Such as sea fish may be associated with an increased risk of developing depression in late life. These factors may be socio-economically and culturally influenced and are therefore amenable to modification. C1 [Fitten, L. J.; Rosenthal, M.; Cole, G. N.] Greater Los Angeles VA Healthcare Syst, Ctr Clin, Los Angeles, CA 91343 USA. [Fitten, L. J.; Ortiz, F.; Fairbanks, L.; Cole, G. N.; Sanchez, M. A.] Univ Calif Los Angeles, David Geffen Sch Med, Alzheimers Dis Res Ctr, Los Angeles, CA 90095 USA. [Fitten, L. J.; Ortiz, F.] Univ Calif Los Angeles, Med Ctr, Dept Psychiat Olive View, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90024 USA. [Fitten, L. J.; Ortiz, F.; Fairbanks, L.; Cole, G. N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Nourhashemi, F.] Purpan Univ Hosp, Fac Med, Toulouse, France. RP Fitten, LJ (reprint author), Greater Los Angeles VA Healthcare Syst, Ctr Clin, Sepulveda Campus,16111 Plummer St,116A-9, Los Angeles, CA 91343 USA. EM jfitten@ucla.edu; freddyo@ucla.edu FU NIA NIH HHS [P50 AG016570, P50 AG16570] NR 48 TC 6 Z9 6 U1 3 U2 8 PU SERDI EDITION PI PARIS PA 320 RUE SAINT-HONORE, PARIS, 75001, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD NOV PY 2008 VL 12 IS 9 BP 634 EP 640 PG 7 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 373IW UT WOS:000260966300005 PM 18953461 ER PT J AU Harber, P Wynn, BO Lim, YW Mattke, S Asch, SM Nuckols, TK AF Harber, Philip Wynn, Barbara O. Lim, Yee-Wei Mattke, Soeren Asch, Steven M. Nuckols, Teryl K. TI Selection of Workers' Compensation Treatment Guidelines: California Experience SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; PHYSICIAN AWARENESS; QUALITY; MANAGEMENT; ADHERENCE AB Objective: Workers' compensation systems increasingly use mandatory treatment guidelines to guide clinicians and for utilization management This article describes steps for selecting such guidelines. Methods: On the basis of experience with the RAND/University of California, Los Angeles project to help California select guidelines, we identified the necessary choices and process for guideline selection and evaluation. Results: Major steps in guideline selection include: 1) define propose; 2) assign decision-making authority; 3) decide whether to use existing guidelines or develop new ones; 4) choose whether to use one or multiple existing guidelines; 5) specify clinical topics that guidelines should address; 6) identify and screen guidelines; 7) evaluate guidelines; 8) consider implications of results; 9) select guideline(s); 10) disseminate selection; and 11) assess long-term effectiveness. Conclusions: Given the many choices required, selecting mandatory workers' compensation guidelines should involve careful planning and a transparent, well-defined process. (J Occup Environ Med. 2008;50:1282-1292) C1 [Harber, Philip] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Div Occupat & Environm Med, Los Angeles, CA 90095 USA. [Harber, Philip] Univ Calif Los Angeles, Sch Publ Hlth, UCLA Ctr Occupat & Environm Hlth, Los Angeles, CA 90024 USA. [Wynn, Barbara O.; Lim, Yee-Wei; Mattke, Soeren; Asch, Steven M.; Nuckols, Teryl K.] RAND Corp, Santa Monica, CA USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.; Nuckols, Teryl K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Asch, Steven M.; Nuckols, Teryl K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Hlth Serv Res, Los Angeles, CA 90095 USA. RP Harber, P (reprint author), 10880 Wilshire Blvd,Suite 1800, Los Angeles, CA 90024 USA. EM pharber@mednet.ucla.edu FU California Department of Industrial Relations; Southern California Education and Research Center (CDC/NIOSH) FX Christine Baker. Executive Officer; Lachlan Taylor, Administrative Law Judge: and Irina Nemirovsky, Research Program Specialist It: of the California Commission oil Health and Safety and Workers' Compensation: and Anne Searcy, Medical Director. of the California Division of Workers' Compensation participated in study conception and design.; Sponsored in part by the California Department of Industrial Relations (Division of Workers' Compensation and the California Commission on Health and Safety and Workers' Compensation) and the Southern California Education and Research Center (CDC/NIOSH). NR 36 TC 3 Z9 3 U1 0 U2 2 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 NOV PY 2008 VL 50 IS 11 BP 1282 EP 1292 DI 10.1097/JOM.0b013e3181841fb4 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 372DC UT WOS:000260880800009 PM 19001954 ER PT J AU Chuang, SK Perrott, DH Susarla, SM Dodson, TB AF Chuang, Sung-Kiang Perrott, David H. Susarla, Srinivas M. Dodson, Thomas B. TI Risk Factors for Inflammatory Complications Following Third Molar Surgery in Adults SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PROPHYLACTIC ANTIBIOTIC-TREATMENT; DRY SOCKET; ALVEOLAR OSTEITIS; REMOVAL; EXTRACTION; NECESSITY; 3RD-MOLAR; OPINION; AGE AB Purpose: To estimate the frequency of inflammatory complications (surgical site infection and alveolar osteitis) following third molar (M3) extraction and identify risk factors for such complications. Materials and Methods: This study was designed as a prospective cohort study and enrolled a sample composed of subjects having >= 1 M3 extracted as part of the American Association of Oral and Maxillofacial Surgeons' Age-Related Third Molar Study. Predictor variables were categorized as demographic, health status, anatomic, and pathologic factors. The outcome variable was the presence of a postoperative inflammatory complication (ie, surgical site infection or alveolar osteitis). Descriptive and bivariate statistics were computed. Variables with P values less than. 15 in bivariate analyses were included in a multiple logistic regression model, used to identify factors associated with inflammatory complications. Results: The study sample consisted of 4,004 subjects with a mean age of 39.8 +/- 13.6 years having 8,748 M3s extracted. In bivariate analyses, impaction level, periodontal disease in or around M3, pre-existing infection around M3, and M3 pathology were associated with postoperative inflammatory complications. In the multiple regression model, level of impaction (soft tissue: odds ratio [OR] = 2.5; 95% confidence interval [CI], 1.7, 3.7), partial bony OR = 4.7 (95% CI, 3.6, 6.1), full bony, 6.0 (95% Cl, 4.7, 7.7); P < .0001), and pre-existing infection (OR = 1.3 [95% CI, 1.0, 1.6; P = .05) or pathology (OR = 3.1; 95% CI, 2.2, 4.3; P < .0001) were associated with an increased risk of inflammatory complications following M3 surgery. Conclusions: Level of impaction, pre-existing infection, and pathology were associated with increased risk for postoperative inflammatory complications following M3 surgery. (C) 2008 American Association of Oral and Maxillofacial Surgeons C1 [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Perrott, David H.] Salinas Valley Mem Healthcare Syst, Salinas, CA USA. [Chuang, Sung-Kiang; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren Bldg 1201, Boston, MA 02114 USA. EM schuang@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 27 TC 21 Z9 25 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2008 VL 66 IS 11 BP 2213 EP 2218 DI 10.1016/j.joms.2008.06.067 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 368FJ UT WOS:000260606700003 PM 18940482 ER PT J AU Sun, T Hunziker, EB Morales, TI AF Sun, Tiezheng Hunziker, Ernst B. Morales, Teresa I. TI Subcellular Distribution of the Insulin-like Growth Factor (IGF) Binding Proteins (IGFBPs) 2 and 3 in Articular Chondrocytes SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE insulin-like growth factor (IGF) binding proteins (IGFBPs); chondrocytes; intracellular; cytoplasmic; nuclear ID RETINOID-X-RECEPTOR; FACTOR BINDING-PROTEIN-3; OSTEOARTHRITIC CARTILAGE; INCREASED EXPRESSION; FACTOR-I; LOCALIZATION; APOPTOSIS; CELLS; INHIBITION; TRANSPORT AB The insulin-like growth factor (IGF) is a major anabolic regulator in articular cartilage. The IGF-binding proteins (IGFBPs) are increased during osteoarthritis (OA), but the function of the later proteins remains unknown. In general, the IGFBPs are pluripotential effectors capable of IGF regulation and of acting on their own to control key cell functions, including, survival and proliferation. The independent functions are often associated with their cell location, and therefore this study explores the distribution of IGFBP-2 and IGFBP-3 in articular chondrocytes. Immunohistochemistry was used to localize IGFBP-2 in normal human articular cartilage. Bovine chondrocytes were used for subcellular fractionation (hypotonic cell lysis) under nonreducing conditions and nuclear purification (centrifugation on sucrose cushions). Cell fraction markers and IGFBPs were assayed in the subcellular Fractions by Western immunoblot. The IHC results showed association of IGFBP-2 with chondrocytes, but not with the nuclei. Subcellular fractionation of isolated chondrocytes yielded intact nuclei as assessed at the light microscopic level; the nuclear marker histone H1 was exclusively associated with this fraction. More than 90% of the cytoplasmic marker GAPDH and all the detectable IGFBP-2 were in the cytoplasmic fraction. Immunoreactive IGFBP-3 was found in the cytoplasmic and peri-nuclear/nuclear fractions. Chondrocytes contain intracellular IGFBP-2 and IGFBP-3 but only IGFBP-3 is associated with nuclei. This suggests the hypothesis that the actions of these IGFBPs in articular cartilage extend beyond the classic modulation of IGF receptor action. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1421-1427, 2008 C1 [Sun, Tiezheng; Morales, Teresa I.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Hunziker, Ernst B.] Univ Bern, Dept Clin Res, DST Res Ctr, CH-3012 Bern, Switzerland. [Morales, Teresa I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Morales, TI (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Jackson Bldg,R1223,55 Fruit St, Boston, MA 02114 USA. EM tmorales@partners.org FU NIAMS, National Institutes of Health [AR48304] FX This work was supported by R01 Grant AR48304 from the NIAMS, National Institutes of Health. T.M. was senior author, but shares lead authorship by protocol development and manuscript writing. NR 34 TC 6 Z9 9 U1 2 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 NOV PY 2008 VL 26 IS 11 BP 1421 EP 1427 DI 10.1002/jor.20660 PG 7 WC Orthopedics SC Orthopedics GA 362KE UT WOS:000260195800001 PM 18418889 ER PT J AU Jupiter, JB AF Jupiter, Jesse B. TI The Management of Nonunion and Malunion of the Distal Humerus-A 30-Year Experience SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE nonunion; distal humerus fracture; stiff elbow; elbow arthroplasty ID SEMICONSTRAINED ELBOW REPLACEMENT; FRACTURES; RECONSTRUCTION; FIXATION; PART AB This personal series of nonunions of the distal humerus reviews unique features of this problem, categorizes them according to unique anatomic features, and presents pitfalls and pearls in the management of these complex reconstructive problems. C1 [Jupiter, Jesse B.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. [Jupiter, Jesse B.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. EM jjupiter@partners.org NR 14 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD NOV-DEC PY 2008 VL 22 IS 10 BP 742 EP 750 DI 10.1097/BOT.0b013e318188d634 PG 9 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 371GO UT WOS:000260820000013 PM 18978552 ER PT J AU Brewer, KL Lee, JW Downs, H Oaklander, AL Yezierski, RP AF Brewer, Kori L. Lee, Jeung Woon Downs, Heather Oaklander, Anne Louise Yezierski, Robert P. TI Dermatomal Scratching After Intramedullary Quisqualate Injection: Correlation With Cutaneous Denervation SO JOURNAL OF PAIN LA English DT Article DE Itch; pruritus; neuropathic pain; spinal cord injury; allodynia; ATF-3 ID SPINAL-CORD-INJURY; NERVE-FIBERS; POSTHERPETIC NEURALGIA; SUPRASPINAL CHANGES; NEUROPATHIC PAIN; SENSORY NEURONS; ITCH; MODEL; RAT; INNERVATION AB Central nervous system lesions cause peripheral dysfunctions currently attributed to central cell death that compromises function of intact peripheral nerves. Injecting quisqualate (QUIS) into the rat spinal cord models spinal cord injury (SCI) and causes at-level scratching and self-injury. Such overgrooming was interpreted to model pain until patients with self-injurious scratching after SCI reported itch motivated scratching that was painless because of sensory loss. Because self-injurious scratching is difficult to explain by central mechanisms alone, we hypothesized that QUIS injections damage peripheral axons of at-level afferents. QUIS was injected into thoracic spinal cords of 18 Long-Evans rats. Animals were killed 3 days after overgrooming began or 14 days after injection. Spinal cord lesions were localized and DRG-immunolabeled for ATF-3. At-level and control skin samples were PGP9.5-immunabeled to quantify axons. Eighty-four percent of QUIS rats overgroomed. Skin in these regions had lost two-thirds of epidermal innervation as compared with controls (P < .001). Rats that overgroomed had 47% less axon-length than nongrooming rats (P = .006). The presence of ATF-3 immunolabeled neurons within diagnosis-related groups of QUIS rats indicated death of afferent cell bodies. Overgrooming after QUIS injections may not be due entirely to central changes. As in humans, self-injurious neuropathic scratching appeared to require loss of protective pain sensations in addition to peripheral denervation. Penpective: This study suggests that intramedullary injection of quisqualic acid in rats causes death of at-level peripheral as well as central neurons. Self-injurious dermatomal scratching that develops in spinal-injured rats may reflect neuropathic itch and loss of protective pain sensations. (C) 2008 by the American Pain Society C1 [Brewer, Kori L.] E Carolina Univ, Dept Emergency Med, Div Res, Brody Sch Med, Greenville, NC 27834 USA. [Lee, Jeung Woon; Downs, Heather] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lee, Jeung Woon; Downs, Heather] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Anesthesia & Neurol, Boston, MA USA. [Yezierski, Robert P.] Univ Florida, Comprehens Ctr Pain Res, Dept Orthodont, Gainesville, FL USA. [Yezierski, Robert P.] Univ Florida, Comprehens Ctr Pain Res, Dept Neurosci, Gainesville, FL USA. RP Brewer, KL (reprint author), E Carolina Univ, Dept Emergency Med, Div Res, Brody Sch Med, PCMH 3ED,600 Moye Blvd, Greenville, NC 27834 USA. EM brewerk@ecu.edu FU NEI NIH HHS [P30 EY 12196, P30 EY012196]; NINDS NIH HHS [R01 NS042866-04, K24NS059892, K24 NS059892-01A1, R01NS42866, K24 NS059892, R01 NS042866] NR 42 TC 16 Z9 16 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 1526-5900 J9 J PAIN JI J. Pain PD NOV PY 2008 VL 9 IS 11 BP 999 EP 1005 DI 10.1016/j.jpain.2008.05.010 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 372PE UT WOS:000260912700005 PM 18619906 ER PT J AU Krakauer, EL AF Krakauer, Eric L. TI Just Palliative Care: Responding Responsibly to the Suffering of the Poor SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; social justice; poverty; AIDS; cancer ID PUBLIC-HEALTH APPROACH; SUB-SAHARAN AFRICA; ANTIRETROVIRAL TREATMENT; HIV/AIDS; CANCER; ETHNICITY; SETTINGS; ACCESS; ATTITUDES; DISTRESS AB The disproportionate suffering of the world's poor from AIDS and cancer has generated efforts to promote palliative care as an affordable alternative to expensive disease-modifying therapies. These well-intentioned efforts stem from a wish to respond to the suffering of the poor as quickly and widely as possible and from the view that only inexpensive interventions are feasible in poor settings. Such efforts also may be informed by the cautious attitude of palliative care in rich countries toward disease-modifying treatment for patients with advanced life-threatening illnesses. Yet, acceptance of unequal access for the poor to life-saving medical services that are badly needed and potentially feasible is unjust. Although palliative interventions to relieve the disproportionate physical, psychological, and social suffering of the poor are essential, they should be integrated with preventive and disease-modifying interventions for major killers, such as acquired immunodeficiency syndrome and cancer. J Pain Symptom Manage 2008;36:505-512. (C) 2008 U. S. Cancer Pain relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. [Krakauer, Eric L.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. RP Krakauer, EL (reprint author), Harvard Univ, Sch Med, Dept Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM eric_krakauer@hms.harvard.edu NR 68 TC 8 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2008 VL 36 IS 5 BP 505 EP 512 DI 10.1016/j.jpainsymman.2007.11.015 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 372QI UT WOS:000260915900007 PM 18971074 ER PT J AU Dupreez, AE Smith, MA Liou, JI Frytak, JR Finch, MD Cleary, JF Kind, AJH AF duPreez, Amanda E. Smith, Maureen A. Liou, Jinn-Ing Frytak, Jennifer R. Finch, Michael D. Cleary, James F. Kind, Amy J. H. TI Predictors of Hospice Utilization among Acute Stroke Patients who Died within Thirty Days SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; NURSING-HOMES; OF-LIFE; INTERNATIONAL-CLASSIFICATION; GEOGRAPHIC-VARIATION; CEREBRAL INFARCTION; ADMINISTRATIVE DATA; DECISION-MAKING; UNITED-STATES; MANAGED CARE AB Background: Hospice is considered to be underutilized, particularly among patients with noncancer diagnoses such as stroke. The highest mortality among stroke patients occurs within the first 30 days; however, we know little about the hospice enrollment decision for this population during this critical time frame. Objectives: To determine hospice enrollment rates and to describe sociodemographic and clinical predictors of hospice utilization among patients who die within 30 days of their stroke. Design: Retrospective analysis of administrative data. Subjects: Medicare beneficiaries 65 years and older discharged with ischemic stroke from 422 hospitals and 11 metropolitan regions during the year 2000 who died within 30 days of their stroke. Measures: Hospice utilization within 30 days. Results: The overall hospice enrollment rate in our study was 23%. Using multivariable logistic regression, factors predicting increased hospice enrollment included older age, female gender, health management organization (HMO) membership, length of stay more than 3 days, and dementia. Factors predicting decreased enrollment included African American race, mechanical ventilation, gastrostomy tube placement, uncomplicated diabetes mellitus, and valvular disease. When in-hospital deaths were excluded, overall enrollment increased to 44%, and mechanical ventilation and dementia ceased to predict enrollment. Conclusions: Hospice enrollment rates among patients who die within the first 30 days of their stroke, particularly among those who survive to discharge, are much higher than prior estimates suggest. Although overall enrollment rates were higher than anticipated, there remain important sociodemographic and clinical characteristics unique to this population that predict low hospice utilization that should serve as targets for further research and intervention. C1 [duPreez, Amanda E.; Smith, Maureen A.; Liou, Jinn-Ing; Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA. [duPreez, Amanda E.] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Womens Hlth Res, Madison, WI 53726 USA. [duPreez, Amanda E.] Meriter Hosp, Madison, WI USA. [duPreez, Amanda E.; Kind, Amy J. H.] William S Middleton Hosp, US Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Finch, Michael D.] Finch & King Inc, Minneapolis, MN USA. [Frytak, Jennifer R.] Ingenix, Eden Prairie, MN USA. [Cleary, James F.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Oncol Sect, Madison, WI 53726 USA. [Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Geriatr Sect, Madison, WI 53726 USA. RP Smith, MA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA. EM maureensmith@wisc.edu FU National Institute of Aging [R01-AG19747] FX This study was supported by a grant (R01-AG19747) from the National Institute of Aging. NR 42 TC 7 Z9 7 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD NOV PY 2008 VL 11 IS 9 BP 1249 EP 1257 DI 10.1089/jpm.2008.0124 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 378AL UT WOS:000261293400021 PM 19021489 ER PT J AU Carlson, MDA Morrison, RS AF Carlson, Melissa D. A. Morrison, R. Sean TI User's Guide to Research in Palliative Care: Why Is a New Series Needed? SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HOSPITALIZED-PATIENTS; ADVANCED DEMENTIA; CONSULTATIONS; ETHICS C1 [Carlson, Melissa D. A.; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr, Hertzberg Palliat Care Inst, New York, NY 10029 USA. [Carlson, Melissa D. A.; Morrison, R. Sean] Natl Palliat Care Res Ctr, New York, NY USA. [Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Carlson, MDA (reprint author), Mt Sinai Sch Med, Brookdale Dept Geriatr, Hertzberg Palliat Care Inst, Box 1070, New York, NY 10029 USA. EM melissa.carlson@mssm.edu FU National Institute for Nursing Research [K99NR10495]; National Institute on Aging [K24AG022345] FX Dr. Carlson is a Brookdale National Fellow, and Olive Branch Scholar of the National Palliative Care Research Center, and the recipient of a Pathway to Independence Award (K99NR10495) from the National Institute for Nursing Research.; Dr. Morrison is the recipient of a Mid-Career Investigator Award in Patient Oriented Research from the National Institute on Aging (K24AG022345). NR 15 TC 9 Z9 9 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD NOV PY 2008 VL 11 IS 9 BP 1258 EP 1261 DI 10.1089/jpm.2008.9831 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 378AL UT WOS:000261293400022 PM 19021490 ER PT J AU Berrios-Rivera, R Rivero-Vergine, A Romero, I AF Berrios-Rivera, Reinaldo Rivero-Vergine, Alicia Romero, Ivonne TI The Pediatric Cancer Hospitalization Experience: Reality Co-constructed SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING LA English DT Article DE hospitalization; pediatric; cancer; psychological factors; lived experiences; biopsychosocial model ID ACUTE LYMPHOBLASTIC-LEUKEMIA; QUALITY-OF-LIFE; LONG-TERM SURVIVORS; CHILDHOOD-CANCER; CHEMOTHERAPY AB Although pediatric cancer treatment has been reviewed by several authors, the lived experiences of children undergoing this process have seldom been discussed in the literature. The data for this article were obtained from a larger qualitative study that provided a collective view of the pediatric cancer experience at San Jorge Children's Hospital in Puerto Rico. In this article, findings that are directly related to the hospitalization process of these young patients are described, including the hospital as a safe haven, dealing with pain, taking control, and thriving in adversity. These findings provide a rationale for the development of a biopsychosocial model of health that emphasizes reciprocal interactions among the biological, psychological, social, cultural, and spiritual dimensions that influence health. C1 [Berrios-Rivera, Reinaldo] Inter Amer Univ Puerto Rico, Dept Educ, Grad Sch Educ, San Juan, PR 00919 USA. [Rivero-Vergine, Alicia] Inter Amer Univ Puerto Rico, Grad Sch Psychol, San Juan, PR 00919 USA. [Romero, Ivonne] Dana Farber Canc Inst, Boston, MA USA. RP Berrios-Rivera, R (reprint author), Inter Amer Univ Puerto Rico, Dept Educ, Grad Sch Educ, Metropolitan Campus,POB 191293, San Juan, PR 00919 USA. EM rberrios22@gmail.com FU San Jorge Children's Research Foundation FX This research was supported by a grant from the San Jorge Children's Research Foundation and additional funds from the Marianist Province of the United States. The authors gratefully acknowledge the contribution of Pilar Belendez, EdD, in the revision of the analysis and research findings and of Laurimar Reveron, MA, research assistant. NR 40 TC 8 Z9 8 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1043-4542 J9 J PEDIATR ONCOL NURS JI J. Pediatr. Oncol. Nurs. PD NOV-DEC PY 2008 VL 25 IS 6 BP 340 EP 353 DI 10.1177/1043454208323618 PG 14 WC Oncology; Nursing SC Oncology; Nursing GA 362ZS UT WOS:000260236300006 PM 18812589 ER PT J AU Heyman, MB Garnett, EA Wojcicki, J Gupta, N Davis, C Cohen, SA Gold, BD Kirschner, BS Baldassano, RN Ferry, GD Winter, HS Kaplan, S AF Heyman, Melvin B. Garnett, Euzabeth A. Wojcicki, Janet Gupta, Neera Davis, Cheryl Cohen, Stanley A. Gold, Benjamin D. Kirschner, Barbara S. Baldassano, Robert N. Ferry, George D. Winter, Harland S. Kaplan, Selna TI Growth Hormone Treatment for Growth Failure in Pediatric Patients with Crohn's Disease SO JOURNAL OF PEDIATRICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; BONE-MINERAL DENSITY; RISK-FACTORS; CHILDREN; THERAPY; ADOLESCENTS; MASS C1 [Heyman, Melvin B.; Garnett, Euzabeth A.; Wojcicki, Janet; Gupta, Neera; Davis, Cheryl; Kaplan, Selna] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Cohen, Stanley A.; Gold, Benjamin D.] Childrens Healthcare Atlanta, Childrens Ctr Digest Healthcare, Atlanta, GA USA. [Gold, Benjamin D.] Emory Univ, Sch Med, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Atlanta, GA USA. [Kirschner, Barbara S.] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. [Baldassano, Robert N.] Childrens Hosp Philadelphia, Div Gastroenterol & Nutr, Philadelphia, PA 19104 USA. [Ferry, George D.] Texas Childrens Hosp, Baylor Coll Med, Clin Care Ctr, Houston, TX 77030 USA. [Winter, Harland S.] MassGen Hosp Children, Dept Pediat, Boston, MA USA. RP Heyman, MB (reprint author), Univ Calif San Francisco, Dept Pediat, 500 Parnassus Ave,MU 4 E,Box 0136, San Francisco, CA 94143 USA. EM mheyman@peds.ucsf.edu FU NCRR NIH HHS [5 M01 RR-01271, M01 RR001271, M01 RR001271-20S10301]; NIDDK NIH HHS [DK 060617, DK007762, DK077734, K23 DK077734, K23 DK077734-01, K24 DK060617, K24 DK060617-03, K24 DK060617-04, K24 DK060617-05, K24 DK060617-06, T32 DK007762, T32 DK007762-28, T32 DK007762-29] NR 26 TC 19 Z9 19 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD NOV PY 2008 VL 153 IS 5 BP 651 EP 658 DI 10.1016/j.jpeds.2008.04.064 PG 8 WC Pediatrics SC Pediatrics GA 372EC UT WOS:000260883600017 PM 18589450 ER PT J AU Albe, E Chang, JH Azar, NF Ivanov, AR Azar, DT AF Albe, Elena Chang, Jin-Hong Azar, Nathalie F. Ivanov, Alexander R. Azar, Dimitri T. TI Proteomic Analysis of the Hyaloid Vascular System Regression during Ocular Development SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE hyaloid vascular system; vasa hyaloidea propria; tunica vasculosa lentis; proteomic analysis; kininogen; angiogenic factors; antiangiogenic factors; vessel regression ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; CELL-GROWTH; APOPTOSIS; NEOVASCULARIZATION; MACROPHAGES; INHIBITION; KININOGEN; MICE; EYE AB We describe a proteomic approach to investigate the differential protein expression patterns and identify the physiologically relevant angiogenic and antiangiogenic factors involved in the hyaloid vascular system regression. Differentially expressed proteins were identified using two-dimensional gel electrophoresis followed by nanoflow chromatography coupled with tandem mass spectrometry. These proteins are expected to provide insight as to their function in the early maintenance and eventual regression of the hyaloid vascular system. C1 [Chang, Jin-Hong; Azar, Nathalie F.; Azar, Dimitri T.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Albe, Elena; Chang, Jin-Hong; Azar, Nathalie F.; Azar, Dimitri T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ivanov, Alexander R.] Harvard Univ, Sch Publ Hlth, Harvard NIEHS Ctr Environm Hlth Proteom Facil, Boston, MA 02115 USA. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu FU S. Elizabeth O'Brien Trust; NIH [EY10101, P30-001792, EY14048]; Research to Prevent Blindness (New York, NY) FX The authors wish to thank Drs. Faisal Tobaigy and Ramon Ghanem for immunoconfocal microscopy. Supported by S. Elizabeth O'Brien Trust (D.TA.), NIH EY10101 (D.TA.), P30-001792 (D.TA.), EY14048 (J.H.C.), and an unrestricted departmental support from Research to Prevent Blindness (New York, NY). NR 46 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV PY 2008 VL 7 IS 11 BP 4904 EP 4913 DI 10.1021/pr800551m PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 370VU UT WOS:000260792000030 PM 18841878 ER PT J AU Pizzagalli, DA Iosifescu, D Hallett, LA Ratner, KG Fava, M AF Pizzagalli, Diego A. Iosifescu, Dan Hallett, Lindsay A. Ratner, Kyle G. Fava, Maurizio TI Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Anhedonia; Depression; Reward processing; Endophenotype; Affect ID ANTERIOR CINGULATE CORTEX; TRIPARTITE MODEL; SIGNAL-DETECTION; REINFORCEMENT SENSITIVITY; BEHAVIORAL ACTIVATION; PREFRONTAL CORTEX; DECISION-MAKING; DOPAMINE; ANXIETY; SYMPTOMS AB Objective: Anhedonia, the lack of reactivity to pleasurable stimuli, is a cardinal feature of depression that has received renewed interest as a potential endophenotype of this debilitating disease. The goal of the present study was to test the hypothesis that individuals with major depression are characterized by blunted reward responsiveness, particularly when anhedonic symptoms are prominent. Methods: A probabilistic reward task rooted within signal-detection theory was utilized to objectively assess hedonic capacity in 23 unmedicated subjects meeting DSM-IV criteria for major depressive disorder (MDD) and 25 matched control subjects recruited from the community. Hedonic capacity was defined as reward responsiveness -i.e., the participants' propensity to modulate behavior as a function of reward. Results: Compared to controls, MDD subjects showed significantly reduced reward responsiveness. Trial-by-trial probability analyses revealed that MDD subjects, while responsive to delivery of single rewards, were impaired at integrating reinforcement history over time and expressing a response bias toward a more frequently rewarded cue in the absence of immediate reward. This selective impairment correlated with self-reported anhedonic symptoms, even after considering anxiety symptoms and general distress. Conclusions: These findings indicate that MDD is characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, and provides initial clues about which aspects of hedonic processing might be dysfunctional in depression. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Pizzagalli, Diego A.; Ratner, Kyle G.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Iosifescu, Dan; Hallett, Lindsay A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Pizzagalli, DA (reprint author), Harvard Univ, Dept Psychol, 1220 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM dap@wjh.harvard.edu FU NIMH [R01MH68376] FX This work was supported by a NIMH grant R01MH68376 awarded to Diego A. Pizzagalli. The NIMH had no further role in study design, data collection and/or analyses, or manuscript preparation. NR 69 TC 169 Z9 171 U1 8 U2 29 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2008 VL 43 IS 1 BP 76 EP 87 DI 10.1016/j.jpsychires.2008.03.001 PG 12 WC Psychiatry SC Psychiatry GA 377UK UT WOS:000261276000010 PM 18433774 ER PT J AU Papakostas, GI Homberger, CH Fava, M AF Papakostas, G. I. Homberger, C. H. Fava, M. TI A meta-analysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE mirtazapine; SSRI; major; depressive; disorder; response ID IMPRESSIONS RATING-SCALE; SHORT-TERM TREATMENT; DOUBLE-BLIND; HAMILTON DEPRESSION; PRIMARY-CARE; PROMOTER POLYMORPHISM; RELATIVE SENSITIVITY; COST-EFFECTIVENESS; RAPID-ONSET; PAROXETINE AB Over the past few years, a number of studies have suggested that the treatment of major depressive disorder (MDD) with anti-depressants enhancing both noradrenergic as well as serotonergic neurotransmission may result in higher response or remission rates than treatment with anti-depressants selectively enhancing serotonergic neurotransmission. The objective of this paper was to compare response rates among patients with MDD treated with either mirtazapine, an anti-depressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or selective serotonin reuptake inhibitors (SSRIs). Medline/Pubmed were searched. No year of publication limits were used. Double-blind, randomized clinical trials comparing mirtazapine with an SSRI for the treatment of MDD. Data were extracted with the use of a pre-coded form. Analyses were performed comparing response rates between the two anti-depressant agents. Data from 10 reports involving a total of 1904 outpatients with MDD were identified and combined using a random-effects model. Patients randomized to treatment with mirtazapine were as likely to experience clinical response as patients randomized to treatment with an SSRI (RR = 1.07; 95% CI: 0.96-1.2, P = 0.181). Simply pooling response rates between the two agents revealed a 67.1% response rate for mirtazapine and a 62.1% response rate for the SSRIs. There was no difference in overall discontinuation rates (RR = 1.1; 95% CI: 0.7-1.5; P = 0.550), discontinuation rates due to adverse events (RR = 0.9; 95% CI: 0.6-1.2; P = 0.497), or discontinuation rates due to lack of efficacy (RR = 0.9; 95% CI: 0.4-2.0; P = 0.871) between the two groups. Fewer mirtazapine-treated patients complained of insomnia (RR = 0.5; 95% CI: 0.3-0.9; P = 0.017), nausea (RR = 0.3; 95% CI: 0.3-0.5; P < 0.0001), whereas fewer SSRI-treated patients complained of fatigue (RR = 1.5; 95% CI: 1.1-2.4; P = 0.028), excessive sleepiness (RR = 1.3; 95% CI: 1.1-1.7; P = 0.020), weight-gain (RR = 3.8; 95% CI: 2.3-6.4; P < 0.0001) or dry mouth (RR = 1.8; 95% CI: 1.3-2.4; P < 0.0001) during the course of treatment. These results suggest that mirtazapine and the SSRIs differ with respect to their side-effect profile but not their overall efficacy in the treatment of MDD. C1 [Papakostas, G. I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH [K23 MH069629] FX Supported, in part, by NIMH Grant K23 MH069629 (GIP). NR 54 TC 31 Z9 33 U1 3 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 EI 1461-7285 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD NOV PY 2008 VL 22 IS 8 BP 843 EP 848 DI 10.1177/0269881107083808 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 377FN UT WOS:000261237200004 PM 18308801 ER PT J AU Kelley, JA AF Kelley, John A. TI The relation between motivational concordance and response expectancy SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Editorial Material C1 [Kelley, John A.] Endicott Coll, Dept Psychol, Beverly, MA 01915 USA. [Kelley, John A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kelley, JA (reprint author), Endicott Coll, Dept Psychol, 376 Hale St, Beverly, MA 01915 USA. EM johnkelley@post.harvard.edu NR 5 TC 2 Z9 2 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD NOV PY 2008 VL 65 IS 5 BP 415 EP 416 DI 10.1016/j.jpsychores.2008.05.001 PG 2 WC Psychiatry SC Psychiatry GA 369IM UT WOS:000260687900002 PM 18940370 ER PT J AU Johnson, TS O'Neill, AC Motarjem, PM Nazzal, J Randolph, M Winograd, JM AF Johnson, T. Shane O'Neill, Anne C. Motarjem, Pejman M. Nazzal, Jamal Randolph, Mark Winograd, Jonathan M. TI Tumor Formation Following Murine Neural Precursor Cell Transplantation in a Rat Peripheral Nerve Injury Model SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE Stem cells; neural precursors; peripheral nerve injury; tumorigenesis ID EMBRYONIC STEM-CELLS; NEUROTROPHIC FACTORS; HUMAN BLASTOCYSTS; NEURONS; DIFFERENTIATION; REGENERATION; REPAIR; LINES; PROGENITORS; BRAIN AB Neural stem cells show a remarkable aptitude for integration and appropriate differentiation at sites of cellular injury in central nervous system (CNS) disease models. In contrast, reports of neural stem cell applications in peripheral nerve injury models are sparse. In this study we sought to determine if the C17.2 cell line would respond to cues in the microenvironment of the injured peripheral nerve and enhance neuronal regeneration in rodent sciatic nerve injury models. We transplanted C17.2 into several sciatic nerve injury models in 45 nude rats, including nerve transection, nerve crush, and nerve gap models. Twelve of the animals in this study developed large tumors at the site of neural stern cell transplants. Histologic-ally, the tumors resembled neuroblastomas. The tumors were confirmed to be of transplanted cell origin by positive P-galactosidase staining. Tumors occurred only in models where the nerve remained intact or where continuity of the nerve was restored. We concluded that C17.2 transplantation into peripheral nerve injury models resulted in a high rate of tumor formation. This study demonstrates that the success of neural precursor transplants in the CNS cannot necessarily be extrapolated to the peripheral nervous system. C1 [Johnson, T. Shane; O'Neill, Anne C.; Motarjem, Pejman M.; Nazzal, Jamal; Randolph, Mark; Winograd, Jonathan M.] Harvard Univ, Sch Med, Plast Surg Res Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Winograd, JM (reprint author), Harvard Univ, Sch Med, Plast Surg Res Lab, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jmwinograd@partners.org NR 24 TC 15 Z9 17 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 NOV PY 2008 VL 24 IS 8 BP 545 EP 550 DI 10.1055/s-0028-1088228 PG 6 WC Surgery SC Surgery GA 375NH UT WOS:000261120100002 PM 18819061 ER PT J AU Luk, J Petrozza, JC AF Luk, Janelle Petrozza, John C. TI Evaluation of Compliance and Range of Fees Among American Society for Reproductive Medicine-Listed Egg Donor and Surrogacy Agencies SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE compensation; compliance; egg donation; egg donor agency; surrogate pregnancy ID GAMETE DONORS; DONATION AB OBJECTIVE: To evaluate the compliance of donor and surrogacy agencies to American Society for Reproductive Medicine (ASRM) guidelines and assess regional differences in agency, donor, and surrogacy fees in the United States. METHODS: A retrospective study was performed Of websites from agencies that have signed an agreement with the Society for Reproductive Technology (SART) to abide by A SRM guidelines in governing egg donor prices and surrogacy compensation. RESULTS: A total of 66 agencies are listed on the website, divided into 8 national regions; 24.5% of egg donor agencies deviated from ASRM guidelines. There was no significant difference in the agency fees among the different regions of United States, but the agency fees for egg donation trend higher in the west. CONCLUSION: A substantial number of egg donor agencies in the United States are not abiding by the ASRM guidelines. Oversight may be needed to correct improper marketing practices for egg donor recruitment. (J Reprod Med 2008;53:847-852) C1 [Petrozza, John C.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Petrozza, JC (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St,Yawkey 10A, Boston, MA 02114 USA. EM jpetrozza@partners.org NR 21 TC 3 Z9 3 U1 0 U2 1 PU J REPROD MED INC PI ST LOUIS PA 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD NOV PY 2008 VL 53 IS 11 BP 849 EP 854 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 376ZR UT WOS:000261222000006 ER PT J AU Yang, CC AF Yang, Claire C. TI The Neurourological Examination in Women SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Physical Examination; Female; Neurourology AB The review provides a description of a physical examination protocol to rule out significant neurologic disease as a cause for a woman's sexual complaints, or to confirm a neurologic cause for the sexual dysfunction, particularly in women with known neurologic disease. Yang CC. The neurourological examination in women. J Sex Med 2008;5:2498-2501. C1 [Yang, Claire C.] Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Yang, Claire C.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Yang, Claire C.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Yang, CC (reprint author), VA Puget Sound Hlth Care Syst, S112-UR,1660 S Columbian Way, Seattle, WA 98108 USA. EM cyang@u.washington.edu NR 7 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD NOV PY 2008 VL 5 IS 11 BP 2498 EP 2501 DI 10.1111/j.1743-6109.2008.01022.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 374UB UT WOS:000261068100005 PM 19006496 ER PT J AU Hartzell, TL Hornicek, FJ Austen, WG AF Hartzell, Tristan L. Hornicek, Francis J. Austen, William G., Jr. TI Latissimus dorsi flap closure of the irradiated clavicular wound SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID CHEST-WALL RECONSTRUCTION; SHOULDER DEFECTS; MUSCLE FLAP; SERRATUS BRANCH; RESECTION; SARCOMA; PEDICLE; BONE; OSTEORADIONECROSIS; BRACHIUM AB Partial or total resection of a previously irradiated clavicle and surrounding soft tissues is a difficult clinical problem. Attempts to close the defect with local tissue often result in wound breakdown and exposure of any remaining clavicle. Furthermore, the most appealing local muscle flap, the pectoralis major, is often unsuitable for reconstruction because of previous resection or radiation damage, Over a 3-year period, 8 patients had resection of a previously irradiated clavicle and surrounding soft tissues. Four underwent excision for sarcoma and four for osteoradionecrosis complicated by chronic wounds. All defects were reconstructed with a pedicled latissimus dorsi muscle flap. No patient hod a flap failure, and all had closed wounds at a minimum 18-month follow-up. Our series demonstrates the success of latissimus dorsi flap coverage for post-claviculectomy defects in on irradiated field. To our knowledge, this is the first described series of such patients. The latissimus dorsi muscle flap should be considered for all difficult wounds involving the clavicle and surrounding soft tissues. (J Shoulder Elbow Surg 2008; 17:875-880.) C1 [Hartzell, Tristan L.] Brigham & Womens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA. [Austen, William G., Jr.] Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, Boston, MA 02114 USA. [Hornicek, Francis J.] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Hartzell, TL (reprint author), Brigham & Womens Hosp, Dept Surg, Div Plast Surg, 75 Francis St, Boston, MA 02115 USA. EM thartzell@partners.org NR 35 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD NOV-DEC PY 2008 VL 17 IS 6 BP 875 EP 880 DI 10.1016/j.jse.2008.04.011 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 376UJ UT WOS:000261208200006 PM 18760634 ER PT J AU Ricketts, T Johnson, E Federman, J AF Ricketts, Todd Johnson, Earl Federman, Jeremy TI Individual Differences within and across Feedback Suppression Hearing Aids SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Feedback suppression; hearing aid; individual differences ID ACOUSTIC FEEDBACK; CANCELLATION; GAIN; ALGORITHMS; SYSTEMS AB Background: New and improved methods of feedback suppression are routinely introduced in hearing aids; however, comparisons of additional gain before feedback (AGBF) values across instruments are complicated by potential variability across subjects and measurement methods. Purpose: To examine the variability in AGBF values across individual listeners and an acoustic manikin. Research Design: A descriptive study of the reliability and variability of the AGBF measured within six commercially available feedback suppression (FS) algorithms using probe microphone techniques. Study Sample: Sixteen participants and an acoustic manikin. Results: The range of AGBF across the six FS algorithms was 0 to 15 dB, consistent with other recent studies. However, measures made in the participants ears and on the acoustic manikin within the same instrument suggest that across instrument comparisons of AGBF measured using acoustic manikin techniques may be misleading, especially when differences between hearing aids are small (i.e., less than 6 dB). Individual subject results also revealed considerable variability within the same FS algorithms. The range of AGBF values was as small as 7 dB and as large as 16 dB depending on the specific FS algorithm, suggesting that some models are much more robust than others. Conclusions: These results suggest caution when selecting FS algorithms clinically since different models can demonstrate similar AGBF when averaging across ears, but result in quite different AGBF values in a single individual ear. C1 [Ricketts, Todd; Federman, Jeremy] Vanderbilt Bill Wilkerson Ctr, Dept Speech & Hearing Sci, Mountain Home, TN USA. [Johnson, Earl] US Dept Vet Affairs, James H Quillen Med Ctr, Mountain Home, TN USA. RP Ricketts, T (reprint author), Dan Maddox Hearing Aid Res Lab, Med Ctr E, 1215 21st Ave S,Room 8310,South Tower, Nashville, TN 37232 USA. EM todd.a.ricketts@vanderbilt.edu FU Siemens Hearing Instruments, Inc FX This study was funded in part by a grant from Siemens Hearing Instruments, Inc. NR 28 TC 4 Z9 4 U1 1 U2 6 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD NOV-DEC PY 2008 VL 19 IS 10 BP 748 EP 757 DI 10.3766/jaaa.19.10.3 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 424IY UT WOS:000264561600003 PM 19358455 ER PT J AU Grelotti, DJ AF Grelotti, David J. TI Clinical Manual for the Treatment of Autism SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Grelotti, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grelotti, DJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dgrelotti@partners.org NR 1 TC 1 Z9 1 U1 0 U2 1 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 NOV PY 2008 VL 47 IS 11 BP 1354 EP 1355 DI 10.1097/01.CHI.0000314037.31103.79 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 365YC UT WOS:000260444800018 ER PT J AU Sun, BK Tsao, H AF Sun, Bryan K. Tsao, Hensin TI Small RNAs in development and disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID GENE-EXPRESSION SIGNATURE; NF-KAPPA-B; BREAST-CANCER; CAENORHABDITIS-ELEGANS; ENZYME DICER; HUMAN GENOME; STEM-CELLS; C-ELEGANS; IN-VIVO; MICRORNA AB MicroRNAs (miRNAs) and short interfering RNAs (siRNAs) are classes of regulatory small RNA molecules, ranging from 18 to 24 nucleotides in length, whose roles in development and disease are becoming increasingly recognized. They function by altering the stability or translational efficiency of messenger RNAs (mRNAs) with which they share sequence complementarity, and are predicted to affect Lip to one-third of all human genes. Computer algorithms and microarray data estimate the presence of nearly 1000 human miRNAs, and direct examination of candidate miRNAs has validated their involvement in various cancers, disorders of neuronal development, cardiac hypertrophy, and skin diseases Such as psoriasis. This article reviews the history of miRNA and siRNA discovery, key aspects of their biogenesis and mechanism of action, and known connections to human health, with an emphasis on their roles in skin development and disease. (J Am Acad Dermatol 2008;59:725-37.) C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Sun, Bryan K.; Tsao, Hensin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Tsao, Hensin] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,50 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org OI Sun, Bryan/0000-0002-0740-0125 NR 61 TC 35 Z9 37 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2008 VL 59 IS 5 BP 725 EP 737 DI 10.1016/j.jaad.2008.08.017 PG 13 WC Dermatology SC Dermatology GA 365CT UT WOS:000260384200001 PM 19119093 ER PT J AU Kimball, AB Resneck, JS AF Kimball, Alexa Boer Resneck, Jack S., Jr. TI The US dermatology workforce: A specialty remains in shortage SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID UNITED-STATES; FEMALE PHYSICIANS; MEDICAL-STUDENTS; RECENT TRENDS; WAIT-TIMES; ACCESS; MELANOMA; GENDER; CHOICE; LONG AB Introduction: Since 1999, multiple surveys have documented a stable undersupply of dermatologic services in the United States. Factors contributing to the imbalance include changes in the demographics of the physician workforce, increased demand for services, and a limited number of training positions for new physicians. In response to the demand, there has also been a substantial influx of nonphysician clinicians into dermatology offices. Methods: We sought to follow tip the large data set collected by the American Academy of Dermatology in 2002; the survey was repeated in 2005. and 2007. Response rates ranged from 30% to 35% and included more than 1200 respondents each year. Results: Few changes were noted in the metrics used to assess the balance of supply and demand in the US dermatology workforce between 2002 and 2007. Mean wait times for new patient appointments decreased slightly from 36 to 33 days. One third of practices continue to seek additional dermatologists. in 2007, 23% of practices reported employing a physician assistant and 10% a nurse practitioner (up from 15% and 8% in 2002). In 2007, typical dermatologists continued to spend the bulk of their direct patient care time in medical dermatology (23.9 hours, 63%), followed by surgery (10.2 hours, 27%), and then cosmetic dermatology (3.8 hours, 10%). A substantial Subset of dermatologists (29%) spent half or more of their time in surgical and cosmetic dermatology combined. Although female dermatologists worked fewer total hours, they spent equal time caring for patients with medical dermatologic conditions, less time in surgical dermatology, and more time in cosmetic dermatology. Limitations: The survey is potentially subject to inaccurate self-report and response bias. Although the results shed light on patient access and the dermatology workforce, they do not establish or quantify any impact on patients' health. Conclusions: Between 2002 and 2007, despite continued increases in the number of nonphysician clinicians in US dermatology offices, there were only small changes in the overall metrics commonly used to assess workforce balance. These findings suggest persistent unmet demand, but, given divergent trends of ongoing increases in surgical and cosmetic dermatology, growth in the use of physician assistants and nurse practitioners, and an aging and expanding US population, the future balance of supply and demand remains difficult to predict. Nevertheless, careful workforce planning and deliberative consideration of the risks and benefits of rapidly emerging changes in the delivery of dermatologic care are essential to ensure access to high-quality care for patients with skin disease. (J Am Acad Dermatol 2008-,59:741-5.) C1 [Kimball, Alexa Boer] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Resneck, Jack S., Jr.] Univ Calif San Francisco, Sch Med, Dept Dermatol, San Francisco, CA 94143 USA. [Resneck, Jack S., Jr.] Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, 50 Staniford St,246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU The American Academy of Dermatology Association FX The American Academy of Dermatology Association funded the administration of the practice profile survey, but our analyses for this manuscript were independently performed. NR 31 TC 76 Z9 76 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2008 VL 59 IS 5 BP 741 EP 745 DI 10.1016/j.jaad.2008.06.037 PG 5 WC Dermatology SC Dermatology GA 365CT UT WOS:000260384200002 PM 18723242 ER PT J AU Buzney, EA Kimball, AB AF Buzney, Elizabeth A. Kimball, Alexa. Boer TI A critical assessment of composite and coprimary endpoints: A complex problem SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID CLINICAL-TRIALS; RANDOMIZED TRIAL; SEVERE PSORIASIS; THERAPY; ISSUES; SELECTION; SEVERITY; OUTCOMES C1 [Kimball, Alexa. Boer] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CURTIS, Boston, MA 02114 USA. [Buzney, Elizabeth A.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa. Boer] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, CURTIS, 50 Staniford St,246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 26 TC 4 Z9 4 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2008 VL 59 IS 5 BP 890 EP 896 DI 10.1016/j.jaad.2008.05.021 PG 7 WC Dermatology SC Dermatology GA 365CT UT WOS:000260384200020 PM 19119103 ER PT J AU Ilyas, AM Mudgal, CS AF Ilyas, Asif M. Mudgal, Chaitanya S. TI Radiocarpal Fracture-dislocations SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID DISTAL RADIUS; ULNAR TRANSLATION; JOINT; PATHOMECHANICS; INSTABILITY; CARPUS; CLASSIFICATION; TRANSLOCATION; LIGAMENTS; FIXATION AB Radiocarpal fracture-dislocations most often are caused by high-energy trauma. These difficult, uncommon injuries involve significant soft-tissue and osseous trauma, requiring meticulous reduction and fixation. The mechanism of injury is generally a severe shear or rotational insult. Anatomically, the dislocation results in disruption of the radiocarpal ligaments and, usually, both the radial and the ulnar styloid. Understanding the anatomy of the radiocarpal joint is central to understanding the osseous and soft-tissue constraints that are disrupted with a radiocarpal dislocation. Diagnosis can be reliably made on physical examination and radiographic evaluation. Radiocarpal fracture-dislocation injuries must be differentiated from Barton fractures. Associated injuries such as open fractures, neurovascular involvement, and distal radioulnar dislocations also must be taken into account. Closed reduction can be obtained relatively easily, but open reduction and internal fixation is typically necessary to ensure accurate anatomic restoration of injured bone and ligaments. C1 [Ilyas, Asif M.] Temple Univ Hosp & Med Sch, Temple Hand Ctr, Philadelphia, PA 19140 USA. [Ilyas, Asif M.] Temple Univ Hosp & Med Sch, Dept Orthopaed Surg & Sports Med, Philadelphia, PA 19140 USA. [Mudgal, Chaitanya S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mudgal, CS (reprint author), Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. NR 46 TC 9 Z9 9 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD NOV PY 2008 VL 16 IS 11 BP 647 EP 655 PG 9 WC Orthopedics SC Orthopedics GA 364UA UT WOS:000260359700005 PM 18978287 ER PT J AU Parchman, ML AF Parchman, Michael L. TI The Gordian Knot of Chronic Illness Care SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Editorial Material ID DIABETES CARE; UNITED-STATES; HEALTH; MANAGEMENT; QUALITY; ADULTS C1 [Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Parchman, Michael L.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Program, San Antonio, TX USA. RP Parchman, ML (reprint author), S Texas Vet Hlth Care, 7400 Merton Mentor Blvd 11C6, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU NIDDK NIH HHS [R18 DK075692] NR 18 TC 3 Z9 3 U1 0 U2 0 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD NOV-DEC PY 2008 VL 21 IS 6 BP 487 EP 489 DI 10.3122/jabfm.2008.06.080180 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 369VH UT WOS:000260721500003 PM 18988714 ER PT J AU Freel, AC Shiloach, M Weigelt, JA Beilman, GJ Mayberry, JC Nirula, R Stafford, RE Tominaga, GT Ko, CY AF Freel, Andrew C. Shiloach, Mira Weigelt, John A. Beilman, Gregory J. Mayberry, John C. Nirula, Rarninder Stafford, Renae E. Tominaga, Gail T. Ko, Clifford Y. TI American College of Surgeons Guidelines Program: A Process for Using Existing Guidelines to Generate Best Practice Recommendations for Central Venous Access SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; MANAGEMENT; APPRAISAL; QUALITY; INSTRUMENT; INSERTION; DEVICES; ADULTS; PAIN AB BACKGROUND: Many professional organizations help their members identify and use quality guidelines. Some of these efforts involve developing new guidelines, and others assess existing guidelines for their clinical usefulness. The American College of Surgeons Guidelines Program attempts to recognize useful surgical guidelines and develop research questions to help clarify existing clinical guidelines. We used existing guidelines about central venous access to develop a set of summary recommendations that could be used by practitioners to establish local best practices. STUDY DESIGN: A comprehensive literature search identified existing clinical guidelines for short-term central venous access. Two reviewers independently rated the guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Highly scored guidelines were analyzed for content, and their recommendations were compiled into a summary table. The summary table was reviewed by an independent panel of experts for clinical utility. RESULTS: Thirty-two guidelines were identified, and 23 met inclusion criteria. The AGREE rating resulted in four guidelines that were strongly recommended and five that were recommended with alterations. Three comprehensive tables of recommendations were produced: procedural, maintenance, and infectious assessment. A panel of experts came to consensus agreement on the final format of the best practice recommendations, which included 30 summary recommendations. CONCLUSIONS: Our process combined assessing existing guidelines methodology with expert opinion to produce a best practice list of guidelines that could be fashioned into local care routines by practicing physicians. The American College of Surgeons guidelines program believes this process will help validate the clinical utility of existing guidelines and identify areas needing further investigation to determine practical validity. (J Am Coll Surg 2008;207:676-682. (C) 2008 by the American College of Surgeons) C1 [Freel, Andrew C.; Shiloach, Mira; Weigelt, John A.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Freel, Andrew C.] Louisiana State Univ, Hlth Sci Ctr, Dept Surg, New Orleans, LA USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Beilman, Gregory J.] Univ Minnesota, Minneapolis, MN USA. [Mayberry, John C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Nirula, Rarninder] Univ Utah, Salt Lake City, UT USA. [Weigelt, John A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Stafford, Renae E.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Tominaga, Gail T.] Scripps Mem Hosp La Jolla, La Jolla, CA USA. RP Shiloach, M (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St, Chicago, IL 60611 USA. OI Beilman, Gregory/0000-0001-5036-3027 FU American College of Surgeons Foundation FX Andrew C Freel participated in the American College of Surgeons Clinical Scholar-in-Residence program from 2006 to 2007. The American College of Surgeons received funding for its Scholars-in-Residence Program from the American College of Surgeons Foundation through a grant from Cook, Inc. NR 28 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 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD NOV PY 2008 VL 207 IS 5 BP 676 EP 682 DI 10.1016/j.jamcollsurg.2008.06.340 PG 7 WC Surgery SC Surgery GA 372SI UT WOS:000260921700008 PM 18954779 ER PT J AU Birkmeyer, JD Shahian, DM Dimick, JB Finlayson, SRG Flum, DR Ko, CY Hall, BL AF Birkmeyer, John D. Shahian, David M. Dimick, Justin B. Finlayson, Samuel R. G. Flum, David R. Ko, Clifford Y. Hall, Bruce Lee TI Blueprint for a New American College of Surgeons: National Surgical Quality Improvement Program SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID BYPASS GRAFT-SURGERY; OF-VETERANS-AFFAIRS; RISK ADJUSTMENT; CARE; OUTCOMES; MORTALITY C1 [Birkmeyer, John D.; Dimick, Justin B.] Univ Michigan, M SCORE, Dept Surg, Ann Arbor, MI 48104 USA. [Hall, Bruce Lee] Washington Univ, Sch Med, St Louis, MO USA. [Hall, Bruce Lee] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Finlayson, Samuel R. G.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Shahian, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Flum, David R.] Univ Washington, Seattle, WA 98195 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Ctr Surg Outcomes & Qual, Los Angeles, CA USA. RP Birkmeyer, JD (reprint author), Univ Michigan, M SCORE, Dept Surg, 211 N 4th Ave, Ann Arbor, MI 48104 USA. NR 14 TC 167 Z9 167 U1 1 U2 4 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 NOV PY 2008 VL 207 IS 5 BP 777 EP 782 DI 10.1016/j.jamcollsurg.2008.07.018 PG 6 WC Surgery SC Surgery GA 372SI UT WOS:000260921700022 PM 18954793 ER PT J AU Chodosh, J Edelen, MO Buchanan, JL Yosef, JA Ouslander, JG Berlowitz, DR Streim, JE Saliba, D AF Chodosh, Joshua Edelen, Maria Orlando Buchanan, Joan L. Yosef, Julia Ann Ouslander, Joseph G. Berlowitz, Dan R. Streim, Joel E. Saliba, Debra TI Nursing Home Assessment of Cognitive Impairment: Development and Testing of a Brief Instrument of Mental Status SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE nursing home; mental status; cognitive assessment; dementia ID MINIMUM DATA SET; DEMENTIA; CARE; RECOGNITION; 3MS; PREVALENCE; RESIDENTS; VALIDITY; SCREEN; OLDER AB To test the accuracy of a brief cognitive assessment of nursing home (NH) residents and to determine whether facility nurses can reliably perform this assessment. Cross-sectional, independent cognitive screening tests with NH residents. Six Department of Veteran Affairs nursing facilities. Three hundred seventy-four residents from six regionally distributed Veteran Affairs NHs. Three cognitive assessment instruments: the Brief Interview of Mental Status (BIMS), created for this study; the Minimum Data Set (MDS) 2.0 Cognitive Performance Scale (CPS), and the Modified Mini-Mental State Examination (3MS) as the criterion standard. The 15-point BIMS tests memory and orientation and includes free and cued recall items. Research assistants administered the 3MS and BIMS to all subjects. Facility nurses administered the same BIMS to a subsample. Three hundred seventy-four of 417 (89.7%) residents approached completed the 3MS and research assistant-administered BIMS (BIMS-R); 212 residents also received a facility nurse-administered BIMS (BIMS-N). The BIMS-R was more highly correlated with the 3MS than was the CPS (Pearson correlation coefficient (r)=0.79 vs 0.62; P <.01 for difference). For the subset who received facility assessments, the BIMS-N was also more highly correlated with the 3MS (Pearson r=0.74 vs 0.65; P <.01 for difference). For any impairment (3MS < 78), the area under the receiver operator characteristic curve (AUC) was 0.86 for the BIMS, versus 0.77 for the CPS. For severe impairment (3MS < 48) the AUC was 0.94, versus 0.85 for the CPS. In this population, a brief cognitive test is a more accurate approach to cognitive assessment than the current observational methods employed using the MDS 2.0. C1 [Chodosh, Joshua; Saliba, Debra] Dept Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. [Chodosh, Joshua; Yosef, Julia Ann; Saliba, Debra] Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv Ctr Excellence, Sepulveda, CA USA. [Chodosh, Joshua; Saliba, Debra] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Dept Med,Multicampus Program Geriatr Med & Geront, Los Angeles, CA 90095 USA. [Edelen, Maria Orlando; Saliba, Debra] Rand Hlth, Santa Monica, CA USA. [Buchanan, Joan L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Ouslander, Joseph G.] Atlanta Dept Vet Affairs Med Ctr, Atlanta, GA USA. [Ouslander, Joseph G.] Emory Univ, Wesley Woods Geriatr Hosp, Atlanta, GA 30322 USA. [Berlowitz, Dan R.] Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Dept Internal Med, Boston, MA USA. [Berlowitz, Dan R.] Boston Univ, Sch Med, Dept Internal Med, Boston, MA 02118 USA. [Streim, Joel E.] Philadelphia Dept Vet Affairs Med Ctr, Mental Illness Res Ctr, Philadelphia, PA USA. [Streim, Joel E.] Philadelphia Dept Vet Affairs Med Ctr, Educ Ctr, Philadelphia, PA USA. [Streim, Joel E.] Philadelphia Dept Vet Affairs Med Ctr, Clin Care Ctr, Philadelphia, PA USA. [Streim, Joel E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Chodosh, J (reprint author), 11301 Wilshire Blvd GRECC,11G, Los Angeles, CA 90073 USA. EM JChodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU Department of Veterans Affairs, Veterans Health Administration Health Services Research and Development Service [SDR 03-217]; Georgia Medical Care Foundation; Pfizer; Novartis; Amgen; Sepracor FX The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this manuscript. This research was supported by the Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service (SDR 03-217). J. Ouslander has a contract with the Georgia Medical Care Foundation, the Medicare Q10 for Georgia; has received grants or funds from Pfizer, Novartis, Amgen, and Sepracor; has been on the speaker forum for Pfizer, Novartis, and Watson; is a consultant to Pfizer, Esprit, and Amgen; and is on the Pfizer Advisory Board. NR 24 TC 34 Z9 35 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2008 VL 56 IS 11 BP 2069 EP 2075 DI 10.1111/j.1532-5415.2008.01944.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 374SS UT WOS:000261064600012 PM 19016941 ER PT J AU Lin, JC Weintraub, N Aragaki, DR AF Lin, James C. Weintraub, Nancy Aragaki, Dixie R. TI Nonsurgical Treatment for Rotator Cuff Injury in the Elderly SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review DE Shoulder pain; rotator cuff disease; elderly ID SUBACROMIAL IMPINGEMENT SYNDROME; SHOCK-WAVE THERAPY; CONTROLLED CLINICAL-TRIAL; SHOULDER PAIN; COMMUNITY SURVEY; SUPRASPINATUS TENDINOPATHY; MUSCULOSKELETAL DISORDERS; CORTICOSTEROID INJECTION; NATURAL-HISTORY; TEARS AB Shoulder pain is a common musculoskeletal complaint in the general population. The elderly population is often afflicted, and rotator cuff problems are among the most common causes of shoulder pain seen in primary care practices. The prevalence of shoulder pain in the elderly has been estimated to range from 21% to 27%, and the prevalence of rotator cuff tear increases with advanced age. The etiology of rotator cuff disease is likely multifactorial, including both extrinsic and intrinsic factors. Rotator cuff dysfunction encompasses a spectrum of pathological changes, ranging from impingement syndrome to rotator cuff tendonitis to rotator cuff tendon tear. In the elderly population, the clinical manifestations from rotator cuff dysfunction can translate into significant morbidity and disabilities, interfering with ability for self care and functional independence. The goals of managing rotator cuff disease are to regain normal shoulder function and biomechanics, and to improve functional abilities in elderly patients. Treatment can consist of various conservative therapies (including ice, simple exercises, medications), and progress to more intensive physical therapy and/or corticosteroid injections. Rotator cuff dysfunction is a common musculoskeletal disorder in elderly patients and is often underdiagnosed and undertreated. Physicians should be aware of the prevalence of rotator cuff disease in this population and provide early diagnosis and treatment to help preserve the functional ability and independence of older patients. (J Am Med Dir Assoc 2008; 9: 626-632) C1 [Lin, James C.; Weintraub, Nancy; Aragaki, Dixie R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Aragaki, Dixie R.] VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA USA. [Weintraub, Nancy] VA Greater Los Angeles Healthcare Syst, Dept Internal Med, Los Angeles, CA USA. RP Weintraub, N (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA, GRECC, 16111 Pkummer St 11E, Sepulveda, CA 91343 USA. EM nancy.weintraub@va.gov NR 58 TC 16 Z9 19 U1 3 U2 21 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 NOV PY 2008 VL 9 IS 9 BP 626 EP 632 DI 10.1016/j.jamda.2008.05.003 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 376ZO UT WOS:000261221700004 PM 18992694 ER PT J AU Kaelber, DC Jha, AK Johnston, D Middleton, B Bates, DW AF Kaelber, David C. Jha, Ashish K. Johnston, Douglas Middleton, Blackford Bates, David W. TI A Research Agenda for Personal Health Records (PHRs) SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID PATIENT-HELD RECORD; INFORMATION-MANAGEMENT; STROKE PATIENTS; MEDICAL-RECORD; PRIMARY-CARE; E-MAIL; IMPLEMENTATION; COMMUNICATION; ATTITUDES; INTERNET AB Patients, policymakers, providers, payers, employers, and others have increasing interest in using personal health records (PHRs) to improve healthcare costs, quality, and efficiency. While organizations now, invest millions of dollars in PHRs, the best PHR architectures, value propositions, and descriptions are not universally agreed upon. Despite widespread interest and activity, little PHR research has been done to date, and targeted research investment in PHRs appears inadequate. The authors reviewed the existing PHR specific literature (100 articles) and divided the articles into seven categories, of which four in particular-evaluation of PHR functions, adoption and attitudes of healthcare providers and patients towards PHRs, PHR related privacy and security, and PHR architecture-present important research opportunities. We also briefly discuss other research related to PHRs, PHR research funding sources, and PHR business models. We believe that additional PHR research can increase the likelihood that future PHR system deployments will beneficially impact healthcare costs, quality, and efficiency. C1 [Kaelber, David C.; Johnston, Douglas; Middleton, Blackford; Bates, David W.] Partners HealthCare Informat Syst, Boston, MA USA. [Kaelber, David C.; Johnston, Douglas; Middleton, Blackford; Bates, David W.] Ctr Informat Technol Leadership, Boston, MA USA. [Kaelber, David C.; Bates, David W.] Ctr Clin & Qual Anal, Boston, MA USA. [Kaelber, David C.; Jha, Ashish K.; Middleton, Blackford; Bates, David W.] Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. [Kaelber, David C.; Jha, Ashish K.; Middleton, Blackford; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Jha, Ashish K.; Middleton, Blackford; Bates, David W.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Kaelber, DC (reprint author), 3158 Kingsley Rd, Shaker Hts, OH 44122 USA. EM david.kaelber@case.edu FU US Advisory Board; Intercomponentware, Inc. FX Dr. Middleton is a paid member of the US Advisory Board for Intercomponentware, Inc., a PHR vendor. The other authors have no financial or commercial relationships that may pose a conflict of interest. NR 145 TC 147 Z9 148 U1 6 U2 49 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 729 EP 736 DI 10.1197/jamia.M2547 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 372MK UT WOS:000260905500004 PM 18756002 ER PT J AU Ijpelaar, DHT Farris, AB Goemaere, N Amann, K Goldschmeding, R Nguyen, TQ Farkash, E van den Heuvel, MC de Heer, E Bruijn, JA Colvin, RB Bajema, IM AF Ijpelaar, Daphne H. T. Farris, Alton B. Goemaere, Natascha Amann, Kerstin Goldschmeding, Roel Nguyen, Tri Q. Farkash, Evan van den Heuvel, Marius C. de Heer, Emile Bruijn, Jan A. Colvin, Robert B. Bajema, Ingeborg M. TI Fidelity and Evolution of Recurrent FSGS in Renal Allografts SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; COLLAPSING GLOMERULOPATHY; VARIANTS; DISEASE; LESION; BIOPSY; TIP AB Five pathologic variants of FSGS were recently defined ("Columbia classification"), but the stability of these phenotypes in renal allografts remains unknown. We hypothesized that if the variants represent distinct diseases, then the pattern of recurrent FSGS in renal allografts will mimic the original disease in the native kidney. This multicenter study included 21 cases of recurrent FSGS from 19 patients who had both native and transplant biopsy samples available for analysis. These results support the Columbia classification, because 81% recurred in the same pattern as the original disease, but three variants manifested plasticity from native to allograft kidneys or in the pattern of recurrence (four FSGS, not otherwise specified [NOS] to collapsing variant, two collapsing variant to FSGS NOS, and one cellular variant to FSGS NOS). No transitions between the cellular and the collapsing variants were observed, supporting the view that these are separate entities. Three categories of recurrence were observed: Type I, recurrence of the same variant of FSGS; type II, recurrence of the same FSGS variant, preceded by a minimal change-like lesion; and type III, recurrence of a different FSGS variant in the allograft. Thus, potential evolution of the pathologic phenotype should be considered in pathologic interpretation and clinical trials. C1 [Ijpelaar, Daphne H. T.; de Heer, Emile; Bruijn, Jan A.; Bajema, Ingeborg M.] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands. [Farris, Alton B.; Farkash, Evan; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Farris, Alton B.; Farkash, Evan; Colvin, Robert B.] Harvard Univ, Sch Med, Boston, MA USA. [Goemaere, Natascha] Erasmus Univ, Dept Pathol, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Amann, Kerstin] Univ Erlangen Nurnberg, Dept Pathol, Erlangen, Germany. [Goldschmeding, Roel; Nguyen, Tri Q.] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands. [van den Heuvel, Marius C.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, NL-9713 AV Groningen, Netherlands. RP Ijpelaar, DHT (reprint author), Leiden Univ, Med Ctr, Dept Pathol, Bldg 1,L1Q,POB 9600, NL-2300 RC Leiden, Netherlands. EM d.ijpelaar@lumc.nl RI Nguyen, Tri/A-9508-2009; De Heer, Emile/C-1110-2009 OI Nguyen, Tri/0000-0001-6475-0706; NR 19 TC 26 Z9 27 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 NOV PY 2008 VL 19 IS 11 BP 2219 EP 2224 DI 10.1681/ASN.2007121365 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 367YI UT WOS:000260588100023 PM 18579640 ER PT J AU Knaus, TA Silver, AM Lindgren, KA Hadjikhani, N Tager-Flusberg, H AF Knaus, Tracey A. Silver, Andrew M. Lindgren, Kristen A. Hadjikhani, Nouchine Tager-Flusberg, Helen TI fMRI activation during a language task in adolescents with ASD SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Autistic disorder; Functional MRI; Broca's area; Wernicke's area; Semantics; Asymmetry ID HIGH-FUNCTIONING AUTISM; WHOLE-BRAIN ANALYSIS; LONG-TERM-MEMORY; SENTENCE COMPREHENSION; CORTICAL ACTIVATION; SPECTRUM DISORDERS; ASSOCIATION CORTEX; COMPLEX SOUNDS; CHILDREN; ADULTS AB Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by language and communication impairments, social impairments, and repetitive behaviors or restricted interests. Previous Studies of semantic functions have found differences in semantic processing and differences in the activation of the language network in adults with ASD compared to controls. The goal Of this Study is to examine semantic functions in adolescents with ASD compared to typically developing adolescents. We utilized fMRI with a reading version of a response-naming task to investigate activation in 12 right-handed adolescent boys with ASD and 12 typically developing boys. Both groups performed the task at ceiling levels. Boys with ASD had significantly stronger activation than controls in Broca's area, which was less left lateralized in ASD individuals. Controls had a significant correlation between frontal and temporal language area activation in the left hemisphere, whereas ASD adolescents did not. Direct group comparisons revealed additional regions activated in the ASD group relative to the control group. These results Suggest differences in semantic organization, approaches to the semantic task, or efficiency in semantic processing in ASD adolescents relative to typically developing adolescents. (JINS, 2008, 14, 967-979.) C1 [Knaus, Tracey A.; Silver, Andrew M.; Lindgren, Kristen A.; Tager-Flusberg, Helen] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Hadjikhani, Nouchine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. RP Knaus, TA (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, 715 Albany St L-814, Boston, MA 02118 USA. EM tknaus@bu.edu RI Hadjikhani, Nouchine/C-2018-2008; Tager-Flusberg, Helen/D-5265-2009 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU National Institute on Deafness and Other Communication Disorders [U19 DC 03610]; NICHD/NIDCD; GCRC at Boston University School of Medicine [M01-RR0533]; NINDS [F30 NS055511] FX This Study was supported by a program project grant from the National Institute on Deafness and Other Communication Disorders (U19 DC 03610), which is part of the NICHD/NIDCD funded Collaborative Programs on Excellence in Autism, as well as funding for the GCRC at Boston University School of Medicine (M01-RR0533). This study was also supported by NINDS F30 NS055511. The authors thank all of their research assistants and Lin Themelis for help with screening and scheduling the participants. They also extend their sincere gratitude to the children and families who participated in this study. NR 49 TC 57 Z9 57 U1 5 U2 16 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 2008 VL 14 IS 6 BP 967 EP 979 DI 10.1017/S1355617708081216 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 372WG UT WOS:000260932400006 PM 18954477 ER PT J AU Saha, S Beach, MC Cooper, LA AF Saha, Somnath Beach, Mary Catherine Cooper, Lisa A. TI Patient Centeredness, Cultural Competence and Healthcare Quality SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE cultural competence; patient-physician relationship; quality of care ID PHYSICIAN RELATIONSHIP; INTERNAL-MEDICINE; FRAMEWORK; RACE AB Cultural competence and patient centeredness are approaches to improving healthcare quality that have been promoted extensively in recent years. In this paper, we explore the historical evolution of both cultural competence and patient centeredness. In doing so, we demonstrate that early conceptual models of cultural competence and patient centeredness focused on how healthcare providers and patients might interact at the interpersonal level and that later conceptual models were expanded to consider how patients might be treated by the healthcare system as a whole. We then compare conceptual models for both cultural competence and patient centeredness at both the interpersonal and healthcare system levels to demonstrate similarities and differences. We conclude that, although the concepts have had different histories and foci, many of the core features of cultural competence and patient centeredness are the same. Each approach holds promise for improving the quality of healthcare for individual patients, communities and populations. C1 [Saha, Somnath] Portland VA Med Ctr, Portland, OR 97239 USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Beach, Mary Catherine; Cooper, Lisa A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Beach, Mary Catherine; Cooper, Lisa A.] Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Saha, S (reprint author), Portland VA Med Ctr, P3MED,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sahas@ohsu.edu FU Commonwealth Fund, a New York; Health Services Research and Development Service of the Department of Veterans Affairs; Robert Wood Johnson Foundation; National Heart Lung and Blood Institute [K24HL083113] FX This study was supported by The Commonwealth Fund, a New York City-based private, independent foundation. Dr. Soho was supported by an Advanced Research Career Development Award from the Health Services Research and Development Service of the Department of Veterans Affairs. Drs. Saha and Beach were supported by Generalist Physician Faculty Scholar Awards from the Robert Wood Johnson Foundation. Dr. Cooper was supported by the National Heart Lung and Blood Institute (grant #K24HL083113). The views expressed in this paper are those of the authors and not necessarily those of The Commonwealth Fund, the Department of Veterans Affairs, the National Institutes of Health or the Robert Wood Johnson Foundation. NR 35 TC 121 Z9 122 U1 3 U2 22 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD NOV PY 2008 VL 100 IS 11 BP 1275 EP 1285 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 374KQ UT WOS:000261042600002 PM 19024223 ER PT J AU Zhou, XH Lin, HZ Johnson, E AF Zhou, Xiao-Hua Lin, Huazhen Johnson, Eric TI Non-parametric heteroscedastic transformation regression models for skewed data with an application to health care costs SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Health care costs; Heteroscedasticity; Non-parametrics; Skewness; Transformation regression models ID 2-PART MODEL; RETRANSFORMATION; LINK; ADO AB We develop a new non-parametric heteroscedastic transformation regression model for predicting the expected value of the outcome of a patient with given patient's covariates when the distribution of the outcome is highly skewed with a heteroscedastic variance. In our model, we allow both the transformation function and the error distribution function to be unknown. We show that under some regularity conditions the estimators for regression parameters, the expected value of the original outcome and the transformation function converge to their true values at the rate n(-1/2). In our simulation studies, we demonstrate that our proposed non-parametric method is robust with little loss of efficiency. Finally, we apply our model to a study on health care costs. C1 [Zhou, Xiao-Hua] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. [Zhou, Xiao-Hua; Johnson, Eric] Univ Washington, Seattle, WA 98195 USA. [Lin, Huazhen] Sichuan Univ, Chengdu 610064, Peoples R China. RP Zhou, XH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. EM azhou@u.washington.edu FU Agency for Healthcare Research and Quality [R01HSO 13105]; US Department of Veterans Affairs; Veterans Affairs Health Administration; Health Services Research Development [ECI-03-206]; Fund of National Natural Science [10771148] FX Zhou's work was supported in part by Agency for Healthcare Research and Quality grant R01HSO 13105 and US Department of Veterans Affairs, Veterans Affairs Health Administration, Health Services Research & Development grant ECI-03-206. Lin's work was supported in part by the Fund of National Natural Science (grant 10771148) of China. We also thank Dr Jurgen Untitzer for providing us with the data. This paper presents tile findings and conclusions or the authors. It does not necessarily represent those of the Veterans Affairs Health Services Research & Development service. We also express our thanks to the Joint Editor, the Associate Editor and the three referees for many helpful comments and suggestions that led to an improvement in this paper. NR 21 TC 2 Z9 2 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-7412 EI 1467-9868 J9 J R STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PD NOV PY 2008 VL 70 BP 1029 EP 1047 DI 10.1111/j.1467-9868.2008.00669.x PN 5 PG 19 WC Statistics & Probability SC Mathematics GA 400EM UT WOS:000262850800008 ER PT J AU Stinchcombe, TE Mauer, AM Hodgson, LD Herndon, JE Lynch, TJ Green, MR Vokes, EE AF Stinchcombe, Thomas E. Mauer, Ann M. Hodgson, Lydia D. Herndon, James E. Lynch, Thomas J. Green, Mark R. Vokes, Everett E. CA Canc & Leukemia Grp B TI Phase II Trial of Paclitaxel and Cisplatin in Patients with Extensive Stage Small Cell Lung Cancer: Cancer and Leukemia Group B Trial 9430 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE CALGB; Paclitaxel; Chemotherapy; Lung cancer; Small cell lung cancer ID COOPERATIVE-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; RANDOMIZED-TRIAL; ETOPOSIDE; CHEMOTHERAPY; CARBOPLATIN; CYCLOPHOSPHAMIDE; DOXORUBICIN; ETOPOSIDE/CISPLATIN; MULTICENTER AB Background: Cancer and Leukemia Group B trial 9430 was a randomized phase II trial which investigated the safety and activity of four novel doublets in untreated extensive stage small cell lung cancer. The results of the paclitaxel and cisplatin arm have not been reported. Patients and Methods: Patients received paclitaxel 230 mg/m(2) followed by cisplatin 75 mg/m(2) onl day 1 every 21 days. All patients received granulocyte colony stimulating factor 5 kg/kg/d beginning on day 3 of each cycle. Results: The patient characteristics of the 34 patients assigned to this treatment arm were: median age 61.5 years (range 41-82), male (76%), performance status 0 (41%), 1 (32%), and 2 (26%). An objective response was observed in 23 patients (68%; 95% confidence interval (CI): 49-83%); 2 complete responses (6%) and 21 partial responses (62%). Median progress ion-free survival time was 5.6 months (95% CI: 4.8-7.1 month), and median overall Survival time was 7.7 months (95% CI: 7.2-12.6 months). The 1-year survival rate observed was 29% (95% CI: 15-45%). Grade 3/4 neutropenia and thrombocytopenia was observed in 5 (15%) and 4 (12%) patients, respectively. Two patients developed febrile neutropenia including one patient who died of neutropenic sepsis. Grade 3/4 nonhematologic observed were: sensory neuropathy in eight patients (24%); and hyperglycemia, malaise and nausea were all observed in four patients (12%). Conclusions: Cancer and Leukemia Group B will not pursue further investigation of paclitaxel and cisplatin due to the modest activity and the toxicity observed on this trial. C1 [Stinchcombe, Thomas E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Multidisciplinary Thorac Oncol Program, Chapel Hill, NC 27599 USA. [Mauer, Ann M.; Vokes, Everett E.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Hodgson, Lydia D.; Herndon, James E.] Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. [Lynch, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Green, Mark R.] Univ Calif San Diego, Dept Hematol Oncol, San Diego, CA 92103 USA. RP Stinchcombe, TE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Multidisciplinary Thorac Oncol Program, 3009 Old Clin Bldg Cb 7305, Chapel Hill, NC 27599 USA. EM Thomas_Stinchcombe@med.unc.edu FU National Cancer Institute [CA31946, CA33601] FX Supported, in part, by the grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 30 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2008 VL 3 IS 11 BP 1301 EP 1307 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 375KT UT WOS:000261113500014 PM 18978566 ER PT J AU Erickson, TM Koeppe, JR Miller, YE Stuart, RW Camidge, DR AF Erickson, Todd M. Koeppe, John R. Miller, York E. Stuart, Rodney W. Camidge, D. Ross TI Bronchioloalveolar Carcinoma Presenting as Chronic Progressive Pulmonary Infiltrates in a Woman with HIV A Diagnosis Worth Making SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE HIV; Human immunodeficiency virus; Bronchioloalveolar carcinoma; Bronchoalveolar carcinoma; BAC; Adenocarcinoma; Lung cancer; Lung carcinoma ID ACTIVE ANTIRETROVIRAL THERAPY; LUNG-CANCER; INFECTED PATIENTS; ERA; IMMUNODEFICIENCY; COHORT AB A 52-year-old woman with human immunodeficiency virus (HIV) developed weight loss, cough, and breathing difficulties, accompanied by extensive bilateral Pulmonary infiltrates. A lengthy infectious disease and autoimmune workup failed to reveal the etiology or produce benefit. Expert pathology review raised the possibility Of pure bronchioloalveolar carcinoma. The patient was treated with erlotinib and achieved a dramatic and prolonged response to treatment. After 14 months a solitary lung nodule developed which was excised. This demonstrated all invasive adenocarcinoma with an activating epidermal growth factor receptor mutation (exon 19 deletion). As this nodule had developed in the presence of erlotinib, this deletion is only presumed to reflect the initial driver of erlotinib sensitivity. Known acquired resistance mechanisms were explored, but the lesion was negative for both exon 20 T790M gatekeeper mutations and cMET gene copy number alterations. An as yet unknown mechanism of acquired resistance is therefore assumed to be involved in this case. We discuss the diagnosis and treatment of lung cancer in HIV-positive Populations and review the general and specific characteristics of bronchioloalveolar carcinoma, including response to epidermal growth factor receptor inhibitors, and known mechanisms of acquired resistance. The predilection for lung cancer in HIV-positive patients, the diffuse nature of bronchioloalveolar carcinoma that can mimic infectious etiologies and the potential for dramatic responses to therapy make this an important diagnosis to consider in this setting. C1 [Erickson, Todd M.; Camidge, D. Ross] Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80202 USA. [Koeppe, John R.] Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80202 USA. [Miller, York E.] Univ Colorado, Hlth Sci Ctr, Dept Pulm Med, Denver, CO 80202 USA. [Miller, York E.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Stuart, Rodney W.] Univ Colorado, Hlth Sci Ctr, Div Pathol, Denver, CO 80202 USA. RP Camidge, DR (reprint author), Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Mail Stop F704,POB 6510, Aurora, CO 80045 USA. EM ross.camidge@uchsc.edu NR 10 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2008 VL 3 IS 11 BP 1353 EP 1355 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 375KT UT WOS:000261113500020 PM 18978572 ER PT J AU Shuja, F Shults, C Duggan, M Tabbara, M Butt, MU Fischer, TH Schreiber, MA Tieu, B Holcomb, JB Sondeen, JL Demoya, M Velmahos, GC Alam, HB AF Shuja, Fahad Shults, Christian Duggan, Michael Tabbara, Malek Butt, Muhammad U. Fischer, Thomas H. Schreiber, Martin A. Tieu, Brandon Holcomb, John B. Sondeen, Jill L. deMoya, Marc Velmahos, George C. Alam, Hasan B. TI Development and Testing of Freeze-Dried Plasma for the Treatment of Trauma-Associated Coagulopathy SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Western-Trauma-Association CY FEB 24-29, 2008 CL Squaw Creek, CA DE Lyophilized; Freeze-dried; Plasma; Blood; Coagulopathy; Acidosis; Hypotherima; Multiple injuries; Resuscitation; Hemodilution; Liver injury; Femur fracture ID FRESH WHOLE-BLOOD; UNCONTROLLED HEMORRHAGIC-SHOCK; COAGULATION-FACTORS; LACTATED RINGERS; POOLED PLASMA; NORMAL SALINE; RESUSCITATION; TRANSFUSIONS; TEMPERATURE; MILITARY AB Background: Trauma-induced coagulopathy is associated with an extremely high mortality. We have recently shown that survival can be improved by correction of coagulopathy through early, aggressive infusion of Fresh Frozen Plasma (FFP). However, FFP is a perishable product, and its use is impractical in challenging environments such as a battlefield. Development of shelf-stable, easy to use, low volume, lyophilized, Freeze-Dried Plasma (FDP) can overcome the logistical limitations. We hereby report the development and testing of such a product. Methods: Plasma separated from fresh porcine blood (n = 10) was either stored as FFP, or lyophilized to produce the FDP. For in vitro testing, the FDP was rehydrated with distilled water and the pH, temperature, and osmolarity were adjusted to match the thawed FFP. Laboratory analysis included measurements of prothrombin time (PT), partial thromboplastin time, fibrinogen levels, and clotting factors II, VII, and IX. To test in vivo efficacy, swine were subjected to multiple injuries (femur fracture and grade V liver injury) and severe hemorrhagic shock (60% blood loss associated with "lethal triad" of coagulopathy, acidosis, and hypothermia), and resuscitated with FFP or FDP (n = 6/group; plasma volumes equal to the volume of shed blood). No treatment, and resuscitation with fresh whole blood served as the control groups (n = 6/group). Coagulation profiles (thromboelastography, PT, partial thromboplastin time, international normalized ratio, fibrinogen) were measured serially during the experiment, and for 4 hours posttreatment. Results: In vitro analysis revealed no differences in the coagulation profiles of FFP and FDP. The lyophilization process did not decrease the activity levels of the measured clotting factors. In the swine model, multiple injuries and hemorrhagic shock caused a 50% to 70% increase in PT (p = 0.03), and infusion of FDP and FFP were equally effective in correcting the coagulopathy. Conclusion: Plasma can be lyophilized and freeze-dried to create a logistically superior product without compromising its hemostatic properties. This product may be suitable for use in austere environments, such as a battlefield, for the treatment of trauma-associated coagulopathy. C1 [Alam, Hasan B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Shults, Christian] Washington Hosp Ctr, Washington, DC 20010 USA. [Fischer, Thomas H.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Schreiber, Martin A.; Tieu, Brandon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Holcomb, John B.; Sondeen, Jill L.] USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA. RP Alam, HB (reprint author), Harvard Univ, Sch Med, 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 44 TC 56 Z9 60 U1 1 U2 5 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 NOV PY 2008 VL 65 IS 5 BP 975 EP 985 DI 10.1097/TA.0b013e3181801cd9 PG 11 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 372DD UT WOS:000260881000002 PM 19001961 ER PT J AU Souza, FF Di Salvo, D AF Souza, Frederico F. Di Salvo, Donald TI Sonographic Features of a Metastatic Extratesticular Gastrointestinal Stromal Tumor SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID PATHOLOGICAL CORRELATION; CARCINOMA; ARCHIVES; MASSES; AFIP AB A gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm that occurs throughout the gastrointestinal tract, mesentery, omentum, and retroperitoneum. We report the sonographic and computed tomographic (CT) features of a case of GIST metastatic to the scrotum and discuss the role of sonography in demonstration and diagnosis of the mass. This report illustrates that the scrotum can be a place for a metastatic GIST; radiologists should be aware of this condition, which could be otherwise mistaken for an extratesticular malignancy arising from other scrotal tissues. C1 [Souza, Frederico F.; Di Salvo, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. RP Souza, FF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02215 USA. EM ffsouza@partners.org NR 14 TC 2 Z9 2 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2008 VL 27 IS 11 BP 1639 EP 1642 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 369AT UT WOS:000260665700015 PM 18946104 ER PT J AU Hu, JC Hevelone, ND Ferreira, MD Lipsitz, SR Choueiri, TK Sanda, MG Earle, CC AF Hu, Jim C. Hevelone, Nathanael D. Ferreira, Marcos D. Lipsitz, Stuart R. Choueiri, Toni K. Sanda, Martin G. Earle, Craig C. TI Patterns of Care for Radical Prostatectomy in the United States From 2003 to 2005 SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatectomy; surgical procedures, minimally invasive; outcome assessment (health care); complications ID ASSISTED LAPAROSCOPIC PROSTATECTOMY; RETROPUBIC PROSTATECTOMY; SINGLE-INSTITUTION; EXPERIENCE; CANCER; OUTCOMES; SURGERY; TRENDS AB Purpose: The demand for minimally invasive radical prostatectomy is increasing, although population based outcomes remain unclear. We assessed use and outcomes in American men undergoing radical prostatectomy. Materials and Methods: We identified 14,727 men undergoing minimally invasive, perineal and retropubic radical prostatectomy during 2003 to 2005 using nationally representative, employer based administrative data. We assessed the association between surgical approach and outcomes, adjusting for age, race, comorbidity and geographic region. Results: Minimally invasive radical prostatectomy use increased from 5.4% to 24.4%, while conversion to open surgery decreased from 28.6% to 4.5% in the 3-year study. Men undergoing minimally invasive and perineal radical prostatectomy vs retropubic radical prostatectomy experienced fewer 30-day complications (14.2% and 14.9% vs 17.5%, p = 0.001), blood transfusions (2.2% and 3.6% vs 9.1%, p < 0.001) and anastomotic strictures (6.8% and 8.5% vs 12.9%, p < 0.001), and shorter median length of stay (I and 2 days, respectively, vs 4, p < 0.001). On adjusted analysis minimally invasive vs retropubic radical prostatectomy was associated with fewer 30-day complications (OR 0.78, 95% CI 0.66, 0.92), transfusions (OR 0.24, 95% CI 0.16, 0.34) and anastomotic strictures (OR 0.50, 95% CI 0.40, 0.62), and shorter length of stay (parameter estimate -0.53, 95% CI -0.58, -0.49). Similarly perineal vs retropubic radical prostatectomy was associated with fewer transfusions (OR 0.50, 95% CI 0.31, 0.82) and anastomotic strictures (OR 0.65, 95% CI 0.47, 0.90), and shorter length of stay (parameter estimate -0.53, 95% CI -0.42, -0.29). Conclusions: While the use of minimally invasive radical prostatectomy surged, men undergoing minimally invasive vs perineal radical prostatectomy experienced a lower risk of 30-day complications, blood transfusions and anastomotic strictures, and a shorter length of stay. Furthermore, perineal vs retropubic radical prostatectomy was also associated with relatively favorable outcomes. Further study is needed to assess continence, potency and cancer control. C1 [Hu, Jim C.; Ferreira, Marcos D.] Harvard Univ, Sch Med, Div Urol Surg, Boston, MA USA. [Hu, Jim C.; Lipsitz, Stuart R.] Harvard Univ, Sch Med, Ctr Surg & Publ Hlth, Boston, MA USA. [Hu, Jim C.; Choueiri, Toni K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Hevelone, Nathanael D.; Earle, Craig C.] Harvard Univ, Sch Med, Ctr Outcomes & Policy Res, Dana Farber Canc Inst, Boston, MA USA. [Sanda, Martin G.] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Div Urol Surg, Boston, MA USA. RP Hu, JC (reprint author), Brigham & Womens Hosp, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA. EM jhu2@partners.org RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; OI Hevelone, Nathanael/0000-0003-4740-2085 FU Lance Armstrong Young Investigator Award; Dana Farber Harvard Cancer Center Career Development Award (JCH) FX Supported by a Lance Armstrong Young Investigator Award and a Dana Farber Harvard Cancer Center Career Development Award (JCH). NR 20 TC 29 Z9 31 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 NOV PY 2008 VL 180 IS 5 BP 1969 EP 1974 DI 10.1016/j.juro.2008.07.054 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 361BH UT WOS:000260102000029 PM 18801512 ER PT J AU Nieder, AM Porter, MP Soloway, MS AF Nieder, Alan M. Porter, Michael P. Soloway, Mark S. TI Radiation Therapy for Prostate Cancer Increases Subsequent Risk of Bladder and Rectal Cancer: A Population Based Cohort Study SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; urinary bladder neoplasms; rectal neoplasms; radiotherapy; prostatectomy ID RADICAL RETROPUBIC PROSTATECTOMIES; 2ND MALIGNANCIES; RADIOTHERAPY; CARCINOMA; CONTINENCE; SURGERY; POTENCY AB Purpose: Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer. We estimated the risk of secondary bladder cancer and rectal cancer after prostate radiotherapy using a contemporary population based cohort. Materials and Methods: We identified 243,082 men in the Surveillance, Epidemiology and End Results database who under-went radical prostatectomy or radiotherapy for prostate cancer between 1988 and 2003. We estimated the incidence rate, standardized incidence ratio and age adjusted incidence rate ratio of subsequent bladder cancer and rectal cancer associated with radical prostatectomy, external beam radiotherapy, brachytherapy, and a combination of external beam radiotherapy and brachytherapy. Results: The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively. Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively. The relative risk of rectal cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.26, 1.08 and 1.21, respectively. The standardized incidence ratio for rectal cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.91, 0.99, 0.68 and 0.86, respectively. Conclusions: Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population. The risk of rectal cancer is increased in patients who receive external beam radiotherapy compared to radical prostatectomy. Patients should be counseled appropriately regarding these risks. C1 [Nieder, Alan M.; Soloway, Mark S.] Univ Miami, Sch Med, Dept Urol, Miami, FL USA. [Porter, Michael P.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Porter, Michael P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Porter, Michael P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Nieder, AM (reprint author), Columbia Univ, Mt Sinai Med Ctr, Div Urol, 4306 Alton Rd,Suite 3014, Miami Beach, FL 33140 USA. EM alan.nieder@columbia.edu NR 17 TC 69 Z9 71 U1 0 U2 7 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 NOV PY 2008 VL 180 IS 5 BP 2005 EP 2009 DI 10.1016/j.juro.2008.07.038 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 361BH UT WOS:000260102000038 PM 18801517 ER PT J AU Lantz, CS Min, B Tsai, M Chatterjea, D Dranoff, G Galli, SJ AF Lantz, Chris S. Min, Booki Tsai, Mindy Chatterjea, Devavani Dranoff, Glenn Galli, Stephen J. TI IL-3 is required for increases in blood basophils in nematode infection in mice and can enhance IgE-dependent IL-4 production by basophils in vitro SO LABORATORY INVESTIGATION LA English DT Article DE allergy; cytokines; immune response; inflammation; mast cells; parasites ID STEM-CELL FACTOR; CHRONIC ALLERGIC INFLAMMATION; MAST-CELLS; T-CELL; INTERLEUKIN-3; IMMUNITY; IDENTIFICATION; ANAPHYLAXIS; RESPONSES; SURVIVAL AB Basophils represent potential effector and immunoregulatory cells, as well as a potential source of IL-4, during the immune response elicited by infection with the nematode Nippostrongylus brasiliensis (N. b.), and in other settings. However, the factors which regulate the numbers of blood basophils in mice, or the ability of these cells to produce IL-4, are not fully understood. We found that infection of mice with the nematodes N. b. or Strongyloides venezuelensis (S. v.) induced substantial increases in the numbers of blood basophils (to as high as 18% of circulating blood leukocytes). Experiments in IL-3(-/-)vs IL-3(+/+) mice, and in IL-3-treated IL-3(-/-)mice, showed that essentially all of the increases in blood or bone marrow basophils during N. b. or S. v. infection were IL-3 dependent. Many of the blood, bone marrow or liver-derived basophils from IL-3(-/-) or IL-3(+/+) mice expressed intracellular IL-4 upon stimulation with anti-IgE in vitro. However, after incubation of the cells with exogenous IgE in vitro, blood-or liver-derived basophils from IL-3(+/+) mice exhibited higher levels of intracellular IL-4 after stimulation with anti-IgE than did basophils derived from IL-3(-/-)mice. Thus, IL-3 is a major regulator of the marked increases in blood basophil levels observed during infection of mice with N. b. or S. v. and also can enhance levels of intracellular IL-4 upon activation of basophils with anti-IgE in vitro. C1 [Tsai, Mindy; Galli, Stephen J.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Lantz, Chris S.] James Madison Univ, Dept Biol, Harrisonburg, VA USA. [Min, Booki] Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. [Chatterjea, Devavani] Macalester Coll, Dept Biol, St Paul, MN 55105 USA. [Dranoff, Glenn] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Galli, SJ (reprint author), Stanford Univ, Sch Med, Dept Pathol, 300 Pasteur Dr,Lane Bldg,L235,MC 5324, Stanford, CA 94305 USA. EM sgalli@stanford.edu FU NIH [AI23990, CA72074, HL67674]; Jeffress Memorial Trust [J-782]; Cleveland Clinic Foundation; American Heart Association FX We thank Fred Finkelman and William Paul and their colleagues for helpful comments. Supported by NIH Grants AI23990, CA72074 and HL67674 to SJG, NIH Grant AI049932 and Jeffress Memorial Trust Grant J-782 to CSL, and startup funds from the Cleveland Clinic Foundation to BM; BM is the recipient of the career development grant from the American Heart Association. NR 31 TC 34 Z9 36 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 2008 VL 88 IS 11 BP 1134 EP 1142 DI 10.1038/labinvest.2008.88 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 365SH UT WOS:000260427600001 PM 18975389 ER PT J AU Ma, J Li, HJ Giovannucci, E Mucci, L Qiu, WL Nguyen, PL Gaziano, JM Pollak, M Stampfer, MJ AF Ma, Jing Li, Haojie Giovannucci, Ed Mucci, Lorelei Qiu, Weiliang Nguyen, Paul L. Gaziano, J. Michael Pollak, Michael Stampfer, Meir J. TI Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis SO LANCET ONCOLOGY LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; INSULIN-RESISTANCE; RADIATION-THERAPY; WEIGHT CHANGE; OBESITY; RISK; HYPERINSULINEMIA; CARCINOMA AB Background Excess body-mass index (BMI) has been associated with adverse outcomes in prostate cancer, and hyperinsulinaemia is a candidate mediator, but prospective data are sparse. We assessed the effect of prediagnostic BMI and plasma C-peptide concentration (reflecting insulin secretion) on prostate cancer-specific mortality after diagnosis. Methods This study involved men diagnosed with prostate cancer during the 24 years of follow-up in the Physicians' Health Study. BMI measurements were available at baseline in 1982 and eight years later in 1990 for 2546 men who developed prostate cancer. Baseline C-peptide concentration was available in 827 men. We used Cox proportional hazards regression models controlling for age, smoking, time between BMI measurement and prostate cancer diagnosis, and competing causes of death to assess the risk of prostate cancer-specific mortality according to BMI and C-peptide concentration. Findings Of the 2546 men diagnosed with prostate cancer during the follow-up period, 989 (38.8%) were overweight (BMI 25.0-29.9 kg/m(2)) and 87 (3.4%) were obese (BMI >= 30 kg/m(2)). 281 men (11%) died from prostate cancer during this follow-up period. Compared with men of a healthy weight (BMI <25 kg/m(2)) at baseline, overweight men and obese men had a significantly higher risk of prostate cancer mortality (proportional hazard ratio [HR] 1.47 [95% CI 1.16-1-88] for overweight men and 2.66 [1.62-4.39] for obese men; p(trend)<0.0001). The trend remained significant after controlling for clinical stage and Gleason grade and was stronger for prostate cancer diagnosed during the PSA screening era (1991-2007) compared with during the pre-PSA screening era (1982-1990) or when using BMI measurements obtained in 1990 compared with those obtained in 1982. Of the 827 men with data available for baseline C-peptide concentration, 117 (14%) died from prostate cancer. Men with C-peptide concentrations in the highest quartile (high) versus the lowest quartile (low) had a higher risk of prostate cancer mortality (HR 2.38 [95% CI 1.31-4.30]; p(trend)=0.008). Compared with men with a BMI less than 25 kg/m(2) and low C-peptide concentrations, those with a BMI of 25 kg/m(2) or more and high C-peptide concentrations had a four-times higher risk of mortality (4.12 [1.97-8.61]; p(interaction)=0.001) independent of clinical predictors. Interpretation Excess bodyweight and a high plasma concentration of C-peptide both predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of their disease. Patients with both factors have the worst outcome. Further studies are now needed to confirm these findings. C1 [Ma, Jing; Giovannucci, Ed; Qiu, Weiliang; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Li, Haojie] GlaxoSmithKline R&D, Worldwide Epidemiol Oncol, Collegeville, PA USA. [Giovannucci, Ed; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Ed; Mucci, Lorelei; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Radiat Oncol Program, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Pollak, Michael] McGill Univ, Jewish Gen Hosp, Canc Prevent Res Unit, Dept Med,Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael] McGill Univ, Jewish Gen Hosp, Canc Prevent Res Unit, Dept Oncol,Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada. RP Ma, J (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu RI Pollak, Michael/G-9094-2011; OI Pollak, Michael/0000-0003-3047-0604; Qiu, Weiliang/0000-0002-9155-6957 FU National Institutes of Health [CA42182, CA90598, CA58684, CA34944, CA40360, HL26490, HL34595]; National Cancer Institute of Canada; Prostate Cancer Foundation, Santa Monica, CA, USA FX The National Institutes of Health research grants CA42182, CA90598, CA58684, CA34944, CA40360, HL26490, HL34595, the National Cancer Institute of Canada, and the Prostate Cancer Foundation, Santa Monica, CA, USA. NR 39 TC 208 Z9 211 U1 1 U2 12 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2008 VL 9 IS 11 BP 1039 EP 1047 DI 10.1016/S1470-2045(08)70235-3 PG 9 WC Oncology SC Oncology GA 370EV UT WOS:000260746400010 PM 18835745 ER PT J AU Silverman, JB Deschler, DG AF Silverman, Joshua B. Deschler, Daniel G. TI A Novel Approach for Dilation of Neopharyngeal Stricture Following Total Laryngectomy Using the Tracheoesophageal Puncture Site SO LARYNGOSCOPE LA English DT Article ID ENDOSCOPIC TECHNIQUE; LARYNGOPHARYNGECTOMY; RECONSTRUCTION; RESTORATION; VOICE C1 [Silverman, Joshua B.; Deschler, Daniel G.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu NR 8 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2008 VL 118 IS 11 BP 2011 EP 2013 DI 10.1097/MLG.0b013e31817fd3dd PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 372AV UT WOS:000260874700019 PM 18758385 ER PT J AU Manstein, D Laubach, H Watanabe, K Farinelli, W Zurakowski, D Anderson, RR AF Manstein, Dieter Laubach, Hans Watanabe, Kanna Farinelli, William Zurakowski, David Anderson, R. Rox TI Selective Cryolysis: A Novel Method of Non-Invasive Fat Removal SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE cryolipolysis; cold; panniculitis; fat removal; pig; selective cryolysis; cryo; body contouring ID CRYOSURGERY; COMPLICATIONS; PANNICULITIS; LIPOSUCTION; HISTORY; DEVICE; LASER AB Background and Objectives: Excess fat poses a host of local and systemic problems. Various energy sources, for example, laser, ultrasound, and radiofrequency electric current have been studied as potential non-invasive treatments aimed at local destruction of subcutaneous fat. Cryosurgery at very low temperatures is routinely used for non-specific tissue destruction, however the potential for tissue-specific cold injury has not been investigated. This study describes non-invasive cold-induced selective destruction of subcutaneous fat. Materials and Methods: Black Yucatan pigs under general anesthesia were exposed within test sites to preset temperatures of 20, -1, -3, -5, and -7 degrees C for 10 minutes. Gross and histological assessments were performed immediately, 1 day, 2, 7, 14 and 28 days post-cold exposure for four pigs, and up to 3.5 months for one pig. Additionally, six pigs were exposed between -5 degrees C and -8 degrees C for 10 minutes, at sites covering approximately 15% body surface area, followed by serum lipid level determinations at various time points up to 3 months. Results: A lobular panniculitis was induced by cooling, followed for some test sites by grossly obvious loss of several mm of subcutaneous fat occurring gradually during the 3.5 months study period. Loss of adipocytes, the appearance of lipid-laden mononuclear inflammatory cells, and local thickening of fibrous septae were noted. Typically there was no clinical or histological evidence of injury to skin, and no scarring. Serum lipids were not significantly increased. Conclusions: Prolonged, controlled local skin cooling can induce selective damage and subsequent loss of subcutaneous fat, without damaging the overlying skin. Selective cryolysis warrants further study as a local treatment for removal of adipose tissue. Lasers Surg. Med. 40:595-604, 2008. (c) 2008Wiley-Liss, Inc. C1 [Manstein, Dieter; Laubach, Hans; Watanabe, Kanna; Farinelli, William; Zurakowski, David; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Manstein, D (reprint author), 50 Blossom St,BHX 630, Boston, MA 02114 USA. EM dmanstein@partners.org FU Zeltiq Aesthetics FX The authors would like to thank Mitch Levinson and others at Zeltiq Aesthetics, Pleasanton, CA for partial support of this study, and for providing one of the prototype devices. In addition, we thank Kathrin Roberts and Margaret E. Sherwood for processing the histological samples and Garuna Kositratna for performing image analysis to determine the lipid area fraction. This study was partially funded by Zeltiq Aesthetics, Royalties from Zeltiq Aesthetics. NR 25 TC 79 Z9 79 U1 2 U2 18 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD NOV PY 2008 VL 40 IS 9 BP 595 EP 604 DI 10.1002/lsm.20719 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 372SN UT WOS:000260922200001 PM 18951424 ER PT J AU Chang, CJ Hsiao, YC Mihm, MC Nelson, JS AF Chang, Cheng-Jen Hsiao, Yen-Chang Mihm, Martin C., Jr. Nelson, J. Stuart TI Pilot Study Examining the Combined Use of Pulsed Dye Laser and Topical Imiquimod Versus Laser Alone for Treatment of Port Wine Stain Birthmarks SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE pulsed dye laser; port wine stain ID HUMAN SKIN; ANGIOGENESIS; EXPOSURE; CREAM AB Background and Objective: The objective of this study was to improve port wine stain (PWS) therapeutic outcome in response to laser therapy. Our specific aim was to determine whether the combined use of pulsed dye laser (PDL) therapy and topical Imiquimod versus PDL alone can improve PWS therapeutic outcome. Study Design/Materials and Methods: This pilot study involved a retrospective review of 20 subjects, all Asian, with PWS. Subject ages ranged between 3 and 56 years. Upon enrollment, three test sites were prospectively identified on each subject for treatment assignments to the following regimens: (A) PDL+Imiquimod; (B) PDL alone; and (C) Imiquimod alone. PDL test sites received a single treatment with a 585 nm wavelength; 1.5 milliseconds pulse duration; spot size 7 mm using a light dosage of 10 J/cm(2) with cryogen spray cooling. For the PE)L+Imiquimod and Imiquimod alone test sites, subjects were instructed to apply Imiquimod topically to the sites once daily for 1 month after PDL exposure. Subjects were followed-up at 1, 3, 6, and 12 months after PDL exposure to evaluate each of the three test sites. The primary efficacy measurement was the quantitative assessment of blanching responses as measured by a DermoSpectrometer to calculate the hemoglobin-index of each site at 1, 3, 6, and 12 months after PDL exposure. Subjects were also closely monitored for any adverse effects. Results: Based on paired sample test analysis, there were clinically, and statistically significant, differences in blanching responses over time favoring PWS receiving PDL+Imiquimod as compared to either PDL or Imiquimod alone (P < 0.05). At 12 months, it should be noted that there was some evidence of redarkening of PWS test sites treated by PDL+Imiquimod and PDL alone, presumably due to revascularization of blood vessels. However, based on comparison of the hemoglobin-indices determined at 1 and 12 months after PDL exposure, there was less revascularization of PWS test sites treated with PI)L+Imiquimod as compared to PDL alone (P < 0.05). Transient hyperpigmentation was noted in 10% (n = 2) and 40% (n = 8) of subjects on the PDL+Imiquimod and PDL alone test sites, respectively. On all sites, hyperpigmentation resolved spontaneously without medical intervention within 6 months. Permanent hypopigmentation or scarring was not observed on any test site. Conclusion: Based on the results of this pilot study, PDL+Imiquimod resulted in superior blanching responses over time as compared to PDL alone for treatment of test sites on PWS lesions. Although the PDL+Imiquimod approach is intriguing, clinical validation in large PWS patient samples is required. Lasers Surg. Med. 40:605610, 2008. (c) 2008 Wiley-Liss, Inc. C1 [Chang, Cheng-Jen; Hsiao, Yen-Chang] Chang Gurg Univ, Chang Gung Mem Hosp, Dept Plast Surg, Taipei, Taiwan. [Mihm, Martin C., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatopathol, Boston, MA USA. [Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92715 USA. RP Chang, CJ (reprint author), Chang Gurg Univ, Chang Gung Mem Hosp, Dept Plast Surg, 199 Tung Hwa N Rd, Taipei, Taiwan. EM chengjen@adm.cgmh.org.tw FU Chang Gung Memorial Hospital [CMRP606, CMRP812]; National Institute of Health [AR47551, EB002495] FX This project was supported by research grants awarded from Chang Gung Memorial Hospital (CMRP606, CMRP812) and the National Institute of Health (AR47551 and EB002495). NR 26 TC 24 Z9 27 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD NOV PY 2008 VL 40 IS 9 BP 605 EP 610 DI 10.1002/lsm.20716 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 372SN UT WOS:000260922200002 PM 18951427 ER PT J AU Upadhyay, J Knudsen, J Anderson, J Becerra, L Borsook, D AF Upadhyay, Jaymin Knudsen, Jamie Anderson, Julie Becerra, Lino Borsook, David TI Noninvasive Mapping of Human Trigeminal Brainstem Pathways SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion tensor imaging; trigeminal nerve; trigeminal ganglion; brainstem; sensory ID GANGLION; MR; TRIGEMINOCEREBELLAR; SYSTEM; IMAGES; HEAT; OPTIMIZATION; REGISTRATION; PROJECTIONS; APPEARANCE AB The human trigeminal system mediates facial pain and somatosensory processing. The anatomic location of neuronal substrates and axonal pathways of the trigeminal system have previously been characterized with conventional in vitro methods. The present investigation implemented diffusion tensor imaging (DTI) and probabilistic tractography to first segment the peripheral trigeminal circuitry, trigeminal nerve branches (ophthalmic, maxillary, and mandibular nerves), ganglion, and nerve root. Subsequent segmentations involved the spinal trigeminal and trigeminal thalamic tracts, which respectively convey information to the spinal trigeminal nuclei and ventral thalamic regions. This latter procedure also identified 1) spinal thalamic (anterolateral [AL]) system pathways (propagating pain and temperature information from the body), 2) trigeminal lemniscus (TL; touch and face position), and 3) medial lemniscus (ML; touch and limb position). The anatomic location of the identified pain and somatosensory pathways compared well with previous functional findings in the human trigeminal system, as well as the tract position in human histological cross sections. Probabilistic tractography may be a useful method to further comprehend the functional and structural properties of trigeminal and other related systems. Application of DTI to map pain and somatosensory pathways in conjunction with a characterization of function properties of pain and somatosensory processing would further define the systematic changes that occur in trigerninal pathology. Magn Reson Med 60: 1037-1046, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Upadhyay, Jaymin; Knudsen, Jamie; Anderson, Julie; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr,PAIN Grp, Belmont, MA 02478 USA. [Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Upadhyay, J (reprint author), Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr,PAIN Grp, 115 Mill St, Belmont, MA 02478 USA. EM jayminu@mclean.harvard.edu FU National Institute of Neurological Disorders and Stroke (NINDS) [5R01NS042721, 5R01NS56195] FX We thank the MR technical staff at teh Mclean Hospital Brain Imaging Center, and Eric Moulton, Ph.D., for helpful discussion during the preparation of this manuscript. This work was support by grants from the National Institute of Neurological Disorders and Stroke (NINDS) (5R01NS042721 and 5R01NS56195: to D.B.). NR 38 TC 22 Z9 24 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2008 VL 60 IS 5 BP 1037 EP 1046 DI 10.1002/mrm.21682 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364NF UT WOS:000260341700004 PM 18956455 ER PT J AU Huang, SY Witzel, T Wald, LL AF Huang, Susie Y. Witzel, Thomas Wald, Lawrence L. TI Accelerated Radiation Damping for Increased Spin Equilibrium (ARISE): A New Method for Controlling the Recovery of Longitudinal Magnetization SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fast imaging; radiation damping; feedback; steady-state free precession; modified Bloch equations ID DRIVEN-EQUILIBRIUM; NMR; FEEDBACK AB Control of the longitudinal magnetization in fast gradient-echo (GRE) sequences is an important factor in enabling the high efficiency of balanced steady-state free precession (bSSFP) sequences. We introduce a new method for accelerating the return of the longitudinal magnetization to the +z-axis that is independent of externally applied RF pulses and shows improved off-resonance performance. The accelerated radiation damping for increased spin equilibrium (ARISE) method uses an external feedback circuit to strengthen the radiation damping (RD) field. The enhanced RD field rotates the magnetization back to the +z-axis at a rate faster than T, relaxation. The method is characterized in GRE phantom imaging at 3T as a function of feedback gain, phase, and duration, and compared with results from numerical simulations of the Bloch equations incorporating RD. A short period of feedback (10 ms) during a refocused interval of a crushed GRE sequence allowed greater than 99% recovery of the longitudinal magnetization when very little T-2 relaxation had time to occur. An appropriate application might be to improve navigated sequences. Unlike conventional flip-back schemes, the ARISE "flip-back" is generated by the spins themselves, thereby offering a potentially useful building block for enhancing GRE sequences. Magn Reson Med 60: 1112-1121, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Huang, Susie Y.; Witzel, Thomas; Wald, Lawrence L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Huang, Susie Y.; Witzel, Thomas; Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Wald, LL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu RI Witzel, Thomas/P-1402-2014; Wald, Lawrence/D-4151-2009 FU NCRR NIH HHS [P41RR14075, P41 RR014075]; NIBIB NIH HHS [R01EB006847, R01 EB006847, R01 EB006847-02]; PHS HHS [R01ED000790] NR 15 TC 6 Z9 6 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2008 VL 60 IS 5 BP 1112 EP 1121 DI 10.1002/mrm.21702 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364NF UT WOS:000260341700012 PM 18956463 ER PT J AU Khachaturian, MH Arsenault, J Ekstrom, LB Tuch, DS Vanduffel, W AF Khachaturian, Mark H. Arsenault, John Ekstrom, Leeland B. Tuch, David S. Vanduffel, Wim TI Focal Reversible Deactivation of Cerebral Metabolism Affects Water Diffusion SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion MRI; cerebral metabolism; reversible deactivation; cooling; MR thermometry; ADC; FA ID MAMMALIAN NERVE FIBERS; FAST AXONAL-TRANSPORT; IN-VIVO; HUMAN BRAIN; WALLERIAN DEGENERATION; COOLING DEACTIVATION; GLUCOSE-UTILIZATION; FUNCTIONAL IMPACT; NEURAL FUNCTION; NORMAL VALUES AB The underlying biophysical mechanisms which affect cerebral diffusion contrast remain poorly understood. We hypothesized that cerebral metabolism may affect cerebral diffusion contrast. The purpose of this study was to develop the methodology to reversibly deactivate cerebral metabolism and measure the effect on the diffusion MRI signal. We developed an MRI-compatible cortical cooling system to reversibly deactivate cortical metabolism in rhesus monkey area V-1 and used MR thermometry to calculate three-dimensional temperature maps of the brain to define the extent of deactivated brain in vivo. Significant changes in the apparent diffusion coefficient (ADC) were only observed during those experiments in which the cortex was cooled below the metabolic cutoff temperature of 20 degrees C. ADC decreases (12-20%) were observed during cortical cooling in regions where the temperature did not change. The normalized in vivo ADC as function of temperature was measured and found to be equivalent to the normalized ADC of free water at temperatures above 20 degrees C, but was significantly decreased below 20 degrees C (20-25% decrease). No changes in fractional anisotropy were observed. In future experiments, we will apply this methodology to quantify the effect of reversible deactivation on neural activity as measured by the hemodynamic response and compare water diffusion changes with hemodynamic changes. Magn Reson Med 60:1178-1189, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Khachaturian, Mark H.; Arsenault, John; Ekstrom, Leeland B.; Tuch, David S.; Vanduffel, Wim] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Khachaturian, Mark H.; Arsenault, John; Ekstrom, Leeland B.] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. [Arsenault, John; Ekstrom, Leeland B.; Tuch, David S.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Arsenault, John; Vanduffel, Wim] Katholieke Univ Leuven, Neuro & Psychofysiol Lab, Louvain, Belgium. RP Khachaturian, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM markk@nmr.mgh.harvard.edu FU IUAP [5/04]; FWO [G-151.04]; HFSPO [CA09502]; NCI [5T32CA09502]; GlaxoSmithkline; Athinoula A. Martinos Foundation; the Mental Illness and Neuroscience Discovery (MIND) Institute; National Alliance for Medical image Computing (NAMIC) [EB05149]; NIH; [5R01EB00790-04]; [EF/05/014] FX The authors thank Thomas Benner, Ken Kwong, Giorgio Bonmasser, Larry Wald, Leonardo Angelone. Andreas Pot-thast. and Helen Deng for their assistance with this project, and Sow Hsin-Chen of the Nuclear Science and Engineering 0 Department at MIT for his helpful discussions oil the hydrodynamics of proteins. This work was supported by 5R01EB00790-04, IUAP 5/04, EF/05/014, FWO G-151.04, HFSPO RGY0014/2002-C, GSKE, NINDS NS46532. NCRR RR14075, NCI CA09502, NCI 5T32CA09502. GlaxoSmithkline, the Athinoula A. Martinos Foundation, the Mental Illness and Neuroscience Discovery (MIND) Institute, and the National Alliance for Medical image Computing (NAMIC) (NIBIB EB05149) which is funded through the NIH Roadmap for Medical Research. NR 56 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2008 VL 60 IS 5 BP 1178 EP 1189 DI 10.1002/mrm.21810 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364NF UT WOS:000260341700018 PM 18958855 ER PT J AU Gnanasekaran, SK Boudreau, AA Soobader, MJ Yucel, R Hill, K Kuhlthau, K AF Gnanasekaran, Sangeeth K. Boudreau, Alexy Arauz Soobader, Mah-J Yucel, Recai Hill, Kristen Kuhlthau, Karen TI State policy environment and delayed or forgone care among children with special health care needs SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE access to care; children with special health care needs ID NATIONAL-SURVEY; LEVEL ANALYSIS; ACCESS; INSURANCE; ENROLLMENT; COVERAGE; FAMILIES; BURDEN AB Objective To evaluate if children with special health care needs (CSHCN) residing in states with more generous public insurance programs were less likely to report delayed or forgone care. Methods We used multilevel modeling to evaluate state policy characteristics after controlling for individual characteristics. We used the 2001 National Survey of CSHCN for individual-level data (N = 33,317) merged with state-level data, which included measures of the state's public insurance programs (Medicaid eligibility and enrollment, spending on Medicaid, SCHIP and Title V, and income eligibility levels), state poverty level and provider supply (including pediatric primary care and specialty providers). We also included a variable for state waivers for CSHCN requiring institutional level care. Results Delayed or forgone care significantly varied among CSHCN between states, net of individual characteristics. Of all the state characteristics studied, only the Medicaid income eligibility levels influenced the risk of experiencing delayed care. CSHCN living in states with higher income eligibility thresholds or more generous eligibility levels were less likely to experience delayed care (OR 0.89(0.80,0.99); P <= 0.05). Conclusions By analyzing child health policy in the context of individual characteristics that may place a child at risk for delayed care, we determined that improving Medicaid eligibility levels improved the process of care for CSHCN. C1 [Gnanasekaran, Sangeeth K.; Boudreau, Alexy Arauz; Hill, Kristen; Kuhlthau, Karen] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02214 USA. [Gnanasekaran, Sangeeth K.; Boudreau, Alexy Arauz; Kuhlthau, Karen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Gnanasekaran, Sangeeth K.] Cambridge Hlth Alliance, Dept Pediat, Cambridge, MA USA. [Soobader, Mah-J] Statworks, Boston, MA USA. [Yucel, Recai] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. RP Gnanasekaran, SK (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02214 USA. EM sgnanasekaran@partners.org FU PHS HHS [T32 HP 10018] NR 24 TC 9 Z9 9 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD NOV PY 2008 VL 12 IS 6 BP 739 EP 746 DI 10.1007/s10995-007-0296-y PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 355UQ UT WOS:000259735000009 PM 17975719 ER PT J AU Babington, L Patel, B AF Babington, Lynn Patel, Bavika TI Understanding child feeding practices of Vietnamese mothers SO MCN-THE AMERICAN JOURNAL OF MATERNAL-CHILD NURSING LA English DT Article DE Obesity; Child feeding; Immigrant; Vietnamese; Focus groups ID OBESITY; OVERWEIGHT; BEHAVIORS; PARENTS; FOCUS AB Purpose: To understand the feeding practices, knowledge, and nutritional beliefs of Vietnamese mothers with young children who are recent immigrants to the United States. Study Design and Methods: Exploratory, descriptive study using a focus group design to provide qualitative data. Twelve Vietnamese mothers of children under the age of 5 years participated in a I-hour focus group discussion (in Vietnamese) facilitated by a Vietnamese nutritionist and the principal investigator Results. The study participants identified that breastfeeding is healthier for babies than formula but reported the difficulty in maintaining breastfeeding due to work and family constraints. A traditional Vietnamese diet of meat or fish with soup broth, vegetables, and rice was the preferred and healthiest diet for children under the age of 6 years. There was consensus in the group that "junk food" and inactivity were unhealthy for children and led to overweight and obesity. Several of the group participants verbalized difficulty in maintaining a healthy diet for their children because the children demanded unhealthy food choices, and their work schedules made it difficult to make sure their children were getting adequate exercise. Clinical Implications. This knowledge can be used by nurses to develop culturally appropriate interventions for immigrants from Vietnam aimed at preventing childhood obesity interventions that consider the effects of acculturation could be more effective when targeted to parents of young children than interventions focused on treatment of obesity in later years. C1 [Babington, Lynn] Northeastern Univ, Boston, MA 02115 USA. [Patel, Bavika] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Babington, L (reprint author), Northeastern Univ, Boston, MA 02115 USA. EM l.babington@neu.edu FU Bouve College of Health Sciences, Northeastern University, Boston, MA FX This study was funded in part by a grant from the Bouve College of Health Sciences, Northeastern University, Boston, MA. NR 30 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-929X J9 MCN-AM J MATERN-CHIL JI MCN-Am. J. Matern.-Child Nurs. PD NOV-DEC PY 2008 VL 33 IS 6 BP 377 EP + PG 6 WC Nursing SC Nursing GA 370DJ UT WOS:000260742600009 ER PT J AU Singer, SJ Falwell, A Gaba, DM Baker, LC AF Singer, Sara J. Falwell, Alyson Gaba, David M. Baker, Laurence C. TI Patient Safety Climate in US Hospitals Variation by Management Level SO MEDICAL CARE LA English DT Article DE safety culture; safety climate; management; leadership ID HEALTH-CARE ORGANIZATIONS; HIGH-HAZARD INDUSTRIES; HIGH-RELIABILITY; RESPONSE RATE; CULTURE; QUESTIONNAIRE; ATTITUDES; DYNAMICS; FAILURES; ROUNDS AB Background: Strengthening hospital safety culture offers promise for reducing adverse events, but efforts to improve Culture may not succeed if hospital managers perceive safety differently from frontline workers. Objectives: To determine whether frontline workers and supervisors perceive a more negative patient safety climate (ie, surface features, reflective of the underlying safety culture) than senior managers in their institutions. To ascertain patterns of variation within management levels by professional discipline. Research Design: A safety climate survey was administered from March 2004 to May 2005 in 92 US hospitals. Individual-level cross sectional comparisons related safety climate to management level. Hierarchical and hospital-fixed effects modeling tested differences in perceptions. Subjects: Random sample of hospital personnel (18,361 respondents). Measures: Frequency of responses indicating absence of safety climate (percent problematic response) overall and for 8 survey dimensions. Results: Frontline workers' safety climate perceptions were 4.8 percentage points (1.4 times) more problematic than were senior managers', and supervisors' perceptions were 3.1 percentage points (1.25 times) more problematic than were senior managers'. Differences were consistent among 7 safety climate dimensions. Differences by management level depended on discipline: senior manager versus frontline worker discrepancies were less pronounced for physicians and more pronounced for nurses, than they were for other disciplines. Conclusions: Senior managers perceived patient safety climate more positively than nonsenior managers overall and across 7 discrete safety climate domains. Patterns of variation by management level differed by professional discipline. Continuing efforts to improve patient safety should address perceptual differences, both among and within groups by management level. 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.; Falwell, Alyson; Gaba, David M.; Baker, Laurence C.] Stanford Univ, Ctr Hlth Policy, Stanford, CA 94305 USA. [Singer, Sara J.; Falwell, Alyson; Gaba, David M.; Baker, Laurence C.] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Gaba, David M.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Gaba, David M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Baker, Laurence C.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 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 Baker, Laurence/0000-0001-5032-794X FU Agency for Healthcare Research and Quality [RO1 HSO 13920] FX Supported by the Agency for Healthcare Research and Quality RO1 HSO 13920. NR 48 TC 53 Z9 53 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2008 VL 46 IS 11 BP 1149 EP 1156 DI 10.1097/MLR.0b013e31817925c1 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 370EQ UT WOS:000260745900004 PM 18953225 ER PT J AU Chen, JY Tao, ML Tisnado, D Malin, J Ko, C Timmer, M Adams, JL Ganz, PA Kahn, KL AF Chen, Judy Y. Tao, May L. Tisnado, Diana Malin, Jennifer Ko, Clifford Timmer, Martha Adams, John L. Ganz, Patricia A. Kahn, Katherine L. TI Impact of Physician-Patient Discussions on Patient Satisfaction SO MEDICAL CARE LA English DT Article ID QUALITY-OF-LIFE; COMPARING TOTAL MASTECTOMY; EARLY BREAST-CANCER; FOLLOW-UP; SURGICAL-TREATMENT; SURGERY; OUTCOMES; TRIAL; RADIOTHERAPY; IRRADIATION AB Background: When 2 treatment choices (ie, mastectomy vs. breast conserving therapy) show no difference in a primary clinical outcome (ie, survival), patient satisfaction becomes an important marker of the quality of care received. Objectives: To assess the impact of physician-patient discussion of primary surgical treatment outcomes on patients' satisfaction with medical care (MC) among women with incident breast cancer (BC). Method: We used self-report data of a population-based survey of 495 women >= 50 years of age with stage I-II BC in Los Angeles, California in 2000 conducted a mean of 7.5 and 24 months after diagnosis. Using multivariable analyses, we evaluated the impact of physician-patient outcome discussions (ie, BC recurrence, BC Survival, breast appearance, and arm swelling/pain/movement difficulty) on patient satisfaction at baseline and follow-up. Results: Most women were satisfied with their MC (>65%). More than half reported physician-patient discussions of BC recurrence (54%), breast appearance (50%), and ann pain/swelling/movement difficulty (55%). Thirty-one percent discussed BC survival. Women who discussed arm swelling, pain, movement difficulty were significantly more likely to be satisfied at baseline (odds ratio: 1.8, 95% confidence interval: 1.1-3.0, P < 0.05) and follow-up (odds ratio: 1.9, 95% confidence interval: 1.2-3.0, P > 0.01). The more treatment outcomes patients discussed with their physicians., the higher patient satisfaction ratings were at baseline and follow-up. Conclusions: Physician-patient discussions of BC treatment outcomes were highly correlated with patients' satisfaction with overall MC regardless of the procedure received. This Suggests that the quality of BC care should include assessments of physician-patient communication. C1 [Chen, Judy Y.] Hlth Benchmarks Inc, Woodland Hills, CA USA. [Tao, May L.] East Bay Partners Canc Care, Antioch, CA USA. [Malin, Jennifer] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Timmer, Martha; Adams, John L.; Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. [Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. RP Kahn, KL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Box 951736,911 Broxton Plaza, Los Angeles, CA 90095 USA. EM kkahn@mednet.ucla.edu FU National Cancer Institute (NCI) [R01 CA8133801A1] FX Supported by the National Cancer Institute (NCI) Grant R01 CA8133801A1. NR 25 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2008 VL 46 IS 11 BP 1157 EP 1162 DI 10.1097/MLR.0b013e31817924bc PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 370EQ UT WOS:000260745900005 PM 18953226 ER PT J AU Cipriano, LE Chesworth, BM Anderson, CK Zaric, GS AF Cipriano, Lauren E. Chesworth, Bert M. Anderson, Chris K. Zaric, Gregory S. TI An Evaluation of Strategies to Reduce Waiting Times for Total Joint Replacement in Ontario SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Meeting of the Institute-for-Operations-Research-and-the-Management-Sciences CT Annual Meeting of the Institute-for-Operations-Research-and-the-Management-Sciences CY NOV, 2007 CY NOV 06, 2007 CL Seattle, WA CL Seattle, WA SP Inst Operat Res & Management Sci SP Inst Operat Res & Management Sci DE queuing; waiting time guarantees; patient prioritization; waiting list management; total joint replacement ID TOTAL HIP-ARTHROPLASTY; KNEE ARTHROPLASTY; ORTHOPEDIC-SURGERY; COST-EFFECTIVENESS; OSTEOARTHRITIS; CANADA; WILLINGNESS; SERVICES; POLICY; RISK AB Background: In 2005, the median waiting time for total hip and knee joint replacements in Ontario was greater than 6 months, which is considered longer than clinically appropriate. Demand is expected to increase and exacerbate already long waiting times. Solutions are needed to reduce waiting times and improve waiting list management. Methods: We developed a discrete event Simulation model of the Ontario total joint replacement system to evaluate the effects of 4 management strategies on waiting times: (1) reductions in surgical demand; (2) formal clinical prioritization; (3) waiting time guarantees; and (4) common waiting list management. Results: If the number of surgeries performed increases by less than 10% each year, then demand must be reduced by at least 15% to ensure that, within 10 years, 90% of patients receive Surgery within their maximum recommended waiting time. Clinically prioritizing patients reduced waiting times for high-priority patients and increased the number of patients at all priority levels who received Surgery each year within recommended maximum waiting times by 9.3%. A waiting time guarantee for all patients provided fewer surgeries within recommended waiting times. Common waiting list management improved efficiency and increased equity in waiting across regions. Discussion: Dramatically increasing the supply of joint replacement surgeries or diverting demand for Surgeries to other jurisdictions will reduce waiting times for total joint replacement surgery. Introducing a strictly adhered to patient prioritization scheme will ensure that more patients receive surgery within severity-specific waiting time targets. Implementing a waiting time guarantee for all patients will not reduce waiting times-it will only shuffle waiting times from some patients to others. To reduce waiting times to clinically acceptable levels within 10 years, increases in the number of surgeries provided greater than those observed historically or reductions in demand are needed. C1 [Zaric, Gregory S.] Univ Western Ontario, Richard Ivey Sch Business, London, ON N6A 3K7, Canada. [Anderson, Chris K.] Cornell Univ, Sch Hotel Adm, Ithaca, NY USA. [Chesworth, Bert M.] Univ Western Ontario, Schulich Sch Med & Dent, Dept Epidemiol & Biostat, London, ON N6A 3K7, Canada. [Chesworth, Bert M.] Univ Western Ontario, Sch Phys Therapy, Fac Hlth Sci, London, ON N6A 3K7, Canada. [Cipriano, Lauren E.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Zaric, GS (reprint author), Univ Western Ontario, Richard Ivey Sch Business, 1151 Richmond St N, London, ON N6A 3K7, Canada. EM gzaric@ivey.uwo.ca RI Zaric, Gregory/B-7665-2013; Chesworth, Herbert/D-4872-2014; Cipriano, Lauren/C-3521-2017 OI Cipriano, Lauren/0000-0001-5568-4516 NR 46 TC 8 Z9 9 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD NOV PY 2008 VL 46 IS 11 BP 1177 EP 1183 DI 10.1097/MLR.0b013e31817925e8 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 370EQ UT WOS:000260745900008 PM 18953229 ER PT J AU Lyatskaya, Y Kadam, D Levitsky, G Hacker, F Chin, L AF Lyatskaya, Yulia Kadam, Dnyanesh Levitsky, Gennady Hacker, Fred Chin, Lee TI Evaluation of a new IR-guided system for mechanical QA of linear accelerators SO MEDICAL PHYSICS LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med DE IR-system; quality assurance; linear accelerator; mechanical isocenter ID RADIATION-THERAPY AB The authors report the development of a new procedure for mechanical quality assurance of linear accelerators using an infrared-guided system. The system consists of an infrared (IR) camera and an IR-reflective marker that can be attached to a gantry, a collimator, or a treatment table. The trace of this marker can be obtained in three dimensions (3D) for a full or partial rotation of the mechanical devices. The software is written to localize rotational axes of the gantry, collimator, and the treatment table based on the marker traces. The separation of these axes characterizes the size of the sphere defining the mechanical isocenter. Additional information on anomalies in gantry movement such as degree of gantry sag and hysteresis can also be obtained. An intrinsic uncertainty of the system to localize rotational axis is 0.35 mm or less. Tests on a linear accelerator demonstrated the ability of this system to detect the separation between rotational axes of less than 1 mm and to confirm orthogonality of the planes of gantry, collimator, and table rotation. (C) 2008 American Association of Physicists in Medicine. [DOI: 10.1118/1.2982148] C1 [Lyatskaya, Yulia; Kadam, Dnyanesh; Levitsky, Gennady; Hacker, Fred; Chin, Lee] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Lyatskaya, Y (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. EM ylyatskaya@lroc.harvard.edu OI Hacker, Fred/0000-0001-7535-7598 NR 7 TC 2 Z9 2 U1 0 U2 3 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 NOV PY 2008 VL 35 IS 11 BP 4816 EP 4823 DI 10.1118/1.2982148 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 366LZ UT WOS:000260484400007 PM 19070214 ER PT J AU Orton, CG Bortfeld, TR Niemierko, A Unkelbach, J AF Orton, Colin G. Bortfeld, Thomas R. Niemierko, Andrzej Unkelbach, Jan TI The role of medical physicists and the AAPM in the development of treatment planning and optimization SO MEDICAL PHYSICS LA English DT Review DE treatment planning; optimization; AAPM; medical physicists; IMRT ID INTENSITY-MODULATED RADIOTHERAPY; COMPLICATION PROBABILITY FACTOR; DYNAMIC MULTILEAF COLLIMATION; RADIATION-THERAPY COMMITTEE; EXTERNAL-BEAM RADIOTHERAPY; INCORPORATING ORGAN MOTION; DOSE-VOLUME HISTOGRAMS; CONFORMAL RADIOTHERAPY; IMRT OPTIMIZATION; ROTATION THERAPY AB Developments in radiotherapy treatment planning and optimization by medical physicists and the American Association of Physicists in Medicine are reviewed, with emphasis on recent work in optimization. It is shown that medical physicists have played a vital role in the creation of innovative treatment planning techniques throughout the past century, most significantly since the advent of computerized tomography for three-dimensional (3D) imaging and high-powered computers capable of 3D planning and optimization. Some early advances in 3D planning made by physicists include development of novel planning algorithms, beam's-eye-view, virtual simulation, dose-volume histogram analysis tools, and bioeffect modeling. Most of the recent developments have been driven by the need to develop treatment planning for conformal radiotherapy, especially intensity modulated radiation therapy. These advances include inverse planning, handling the effects of motion and uncertainty, biological planning, and multicriteria optimization. (C) 2008 American Association of Physicists in Medicine. [DOI: 10.1118/1.2990777] C1 [Orton, Colin G.] Wayne State Univ, Detroit, MI 48201 USA. [Bortfeld, Thomas R.; Niemierko, Andrzej; Unkelbach, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Orton, CG (reprint author), Wayne State Univ, Detroit, MI 48201 USA. EM ortonc@comcast.net NR 132 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD NOV PY 2008 VL 35 IS 11 BP 4911 EP 4923 DI 10.1118/1.2990777 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 366LZ UT WOS:000260484400018 PM 19070225 ER PT J AU Styer, AK AF Styer, Aaron K. TI Menopausal status and physical performance in midlife: simple correlation or multifactorial continuum? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID BRITISH BIRTH COHORT; GRIP STRENGTH; WOMEN; AGE; HEALTH; MEN C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Styer, AK (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1043 EP 1044 DI 10.1097/GME.0b013e318186d813 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500006 PM 19009683 ER PT J AU Avis, NE Legault, C Coeytaux, RR Pian-Smith, M Shifren, JL Chen, WN Valaskatgis, P AF Avis, Nancy E. Legault, Claudine Coeytaux, Remy R. Pian-Smith, May Shifren, Jan L. Chen, Wunian Valaskatgis, Peter TI A randomized, controlled pilot study of acupuncture treatment for menopausal hot flashes SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Acupuncture; Vasomotor symptoms; Hot flashes ID QUALITY-OF-LIFE; MIDDLE-AGED WOMEN; HORMONE REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; ALTERNATIVE THERAPIES; VASOMOTOR SYMPTOMS; POSTMENOPAUSAL WOMEN; CONTROLLED TRIAL; BREAST-CANCER; HEALTH AB Objective: To investigate the feasibility of conducting a randomized trial of the effect of acupuncture in decreasing hot flashes in peri- and postmenopausal women. Design: Fifty-six women ages 44 to 55 with no menses in the past 3 months and at least four hot flashes per day were recruited from two clinical centers and randomized to one of three treatment groups: usual care (n = 19), sham acupuncture (n = 18), or Traditional Chinese Medicine acupuncture (n = 19). Acupuncture treatments were scheduled twice weekly for 8 consecutive weeks. The sham acupuncture group received shallow needling in nontherapeutic sites. The Traditional Chinese Medicine acupuncture group received one of four treatments based oil a Traditional Chinese Medicine diagnosis. Usual care participants were instructed to not initiate any new treatments for hot flashes during the study. Daily diaries were used to track frequency and severity of hot flashes. The mean daily index score was based oil the number of mild, moderate, and severe hot flashes. Follow-up analyses were adjusted for baseline values, clinical center. age, and body mass index. Results: There was a significant decrease in mean frequency of hot flashes between weeks 1 and 8 across all groups (P =0.01), although the differences between the three Study groups were not significant. However, the two acupuncture groups showed a significantly greater decrease than the usual care group (P < 0.05), but did not differ from each other. Results followed a similar pattern for the hot flash index score. There were no significant effects for changes in hot flash interference, sleep, mood, health-related quality of life, or psychological well-being Conclusions: These results suggest either that there is a strong placebo effect or that both traditional and sham acupuncture significantly reduce hot flash frequency. C1 [Avis, Nancy E.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Dept Social Sci & Hlth Policy, Winston Salem, NC 27157 USA. [Legault, Claudine] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Coeytaux, Remy R.; Chen, Wunian] Univ N Carolina, Chapel Hill, NC USA. [Pian-Smith, May; Shifren, Jan L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pian-Smith, May; Shifren, Jan L.] Harvard Univ, Sch Med, Boston, MA USA. [Valaskatgis, Peter] New England Sch Acupuncture, Newton, MA USA. RP Avis, NE (reprint author), Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Dept Social Sci & Hlth Policy, Piedmont Plaza 2,2nd Floor, Winston Salem, NC 27157 USA. EM navis@wfubmc.edu FU National Cancer Institute [R21 CA 104427]; Massachusetts General Hospital [M01-RR-0166]; National Institutes of Health; National Center for Research Resources; General Clinical Research Centers Program and at the University of North Carolina [RR000046] FX Research support by grant R21 CA 104427 front the National Cancer Institute. Support was provided at Massachusetts General Hospital by Grant Number M01-RR-0166, National Institutes of Health, National Center for Research Resources, General Clinical Research Centers Program and at the University of North Carolina by Grant RR000046 at the Verne S. Caviness General Clinical Research Center at UNC School of Medicine. NR 46 TC 53 Z9 55 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1070 EP 1078 DI 10.1097/gme.0b013e31816d5b03 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500012 PM 18528313 ER PT J AU Warden, SJ Nelson, IR Fuchs, RK Bliziotes, MM Turner, CH AF Warden, Stuart J. Nelson, Ian R. Fuchs, Robyn K. Bliziotes, Michael M. Turner, Charles H. TI Serotonin (5-hydroxytryptamine) transporter inhibition causes bone loss in adult mice independently of estrogen deficiency SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Antidepressants; Depression; Neurotransmitter; Osteoporosis; Prozac; Serotonin selective reuptake inhibitor ID MINERAL DENSITY; REUPTAKE INHIBITORS; OLDER WOMEN; MECHANICAL-PROPERTIES; FLUOXETINE TREATMENT; HIP-FRACTURES; ANTIDEPRESSANTS; RISK; DEPRESSION; ASSOCIATION AB Objective: Selective serotonin reuptake inhibitors (SSRIs) treat depression by antagonizing the serotonin (5-hydroxytryptamine) transporter (5-HTT). These drugs may also have skeletal effects given the presence of functional serotonergic pathways in bone and evidence demonstrating detrimental effects of SSRIs on postmenopausal bone changes. This Study aimed to explore the influence of an SSRI (fluoxetine hydrochloride) oil the bone changes associated with estrogen deficiency in adult mice. Design: Adult, female, Swiss-Webster mice underwent ovariectomy (OVX) or sham OVX and were treated daily for 4 weeks with either fluoxetine hydrochloride (5 or 20 mg/kg) or a vehicle solution (control). In vivo assessments of hindlimb areal and tibial volumetric bone mineral density were performed at baseline and after 4 weeks of intervention. Femurs and lumbar vertebrae were subsequently removed and assessed ex vivo for bone mineral density and trabecular bone architecture and turnover. Results: In vivo and ex vivo skeletal measures found no interactions between OVX (estrogen deficiency) and 5-HTT inhibition, indicating that the skeletal effects of these interventions were independent. 5-HTT inhibition had detrimental skeletal effects, with the fluoxetine-treated groups having reduced bone mineral density and altered trabecular architecture. These changes resulted from both a decrease in bone formation and increase in bone resorption. Conclusions: These data indicate that a commonly prescribed SSRI has a negative influence on the adult skeleton, independent of estrogen deficiency. This finding Supports clinical data demonstrating SSRI use to be associated with accelerated bone loss after menopause and highlights a need for further research into the skeletal effects of SSRIs. C1 [Warden, Stuart J.; Nelson, Ian R.; Fuchs, Robyn K.] Indiana Univ, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Indianapolis, IN 46202 USA. [Warden, Stuart J.; Fuchs, Robyn K.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Bliziotes, Michael M.] Portland VA Med Ctr, Portland, OR USA. [Bliziotes, Michael M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Turner, Charles H.] Indiana Univ Purdue Univ, Purdue Sch Engn & Technol, Dept Biomed Engn, Indianapolis, IN 46202 USA. RP Warden, SJ (reprint author), Indiana Univ, Sch Hlth & Rehabil Sci, Dept Phys Therapy, 1140 W Michigan St,CF-326, Indianapolis, IN 46202 USA. EM stwarden@iupui.edu RI Warden, Stuart/C-5287-2012; OI Warden, Stuart/0000-0002-6415-4936 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR-052018] FX Funding/support: This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-052018). NR 44 TC 34 Z9 38 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1176 EP 1183 DI 10.1097/gme.0b013e318173566b PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500027 PM 18725867 ER PT J AU Shifren, JL AF Shifren, Jan L. TI Treatment of Sexual Desire Disorder During Peri- and Postmenopause SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 19th Annual Meeting of the North-American-Menopause-Society CY SEP 24-27, 2008 CL Orlando, FL SP N Amer Menopause Soc C1 [Shifren, Jan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, 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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1202 EP 1202 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500061 ER PT J AU Joffe, H Petrillo, LF Koukopolous, A Viguera, AC Hirschberg, A Nonacs, R Somley, B Pasciullo, E White, DP Hall, JE Cohen, LS AF Joffe, Hadine Petrillo, Laura F. Koukopolous, Alexia Viguera, Adele C. Hirschberg, April Nonacs, Ruta Somley, Brittny Pasciullo, Erica White, David P. Hall, Janet E. Cohen, Lee S. TI Improved Sleep and Increased Estradiol, but Not Hot Flashes, Predict Enhanced Mood during the Menopausal Transition SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 19th Annual Meeting of the North-American-Menopause-Society CY SEP 24-27, 2008 CL Orlando, FL SP N Amer Menopause Soc C1 [Joffe, Hadine; Petrillo, Laura F.; Koukopolous, Alexia; Viguera, Adele C.; Hirschberg, April; Nonacs, Ruta; Somley, Brittny; Pasciullo, Erica; Cohen, Lee S.] Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. [White, David P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med,Dept Med, Boston, MA 02115 USA. [Hall, Janet E.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1216 EP 1216 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500111 ER PT J AU Joffe, H Lin, N Deckersbach, T McCumin, KE Jameson, ML Fischman, AJ Dougherty, DD Hall, JE AF Joffe, Hadine Lin, Nancy Deckersbach, Thilo McCumin, Kristin E. Jameson, Mariko L. Fischman, Alan J. Dougherty, Darin D. Hall, Janet E. TI PET Studies Reveal Increased Activity in the Hypothalamus and Insular Cortex Prior to the Development of Hot Flashes SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 19th Annual Meeting of the North-American-Menopause-Society CY SEP 24-27, 2008 CL Orlando, FL SP N Amer Menopause Soc C1 [Joffe, Hadine] Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. [Lin, Nancy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Deckersbach, Thilo; Jameson, Mariko L.; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Program, Boston, MA 02114 USA. [McCumin, Kristin E.; Hall, Janet E.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Fischman, Alan J.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med PET, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1216 EP 1216 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500110 ER PT J AU Thurston, RC Sternfeld, B Sowers, M Bromberger, J Gold, E Chang, YF Joffe, H Crandall, C Waetjen, E Matthews, K AF Thurston, Rebecca C. Sternfeld, Barbara Sowers, MaryFran Bromberger, Joyce Gold, Ellen Chang, Yuefang Joffe, Hadine Crandall, Carolyn Waetjen, Elaine Matthews, Karen TI Gains in Body Fat and Onset of Hot Flashes over Time: A Longitudinal Analysis of the Study of Women's Health across the Nation SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 19th Annual Meeting of the North-American-Menopause-Society CY SEP 24-27, 2008 CL Orlando, FL SP N Amer Menopause Soc C1 [Thurston, Rebecca C.; Bromberger, Joyce; Chang, Yuefang; Matthews, Karen] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA USA. [Sowers, MaryFran] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Gold, Ellen; Waetjen, Elaine] Univ Calif Davis, Davis Med Ctr, Davis, CA 95616 USA. [Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Crandall, Carolyn] David Geffen UCLA, Sch Med, Los Angeles, CA 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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1225 EP 1225 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500145 ER PT J AU Cohen, LS Soares, CN Pasciullo, E Silver, M Joffe, H AF Cohen, Lee S. Soares, Claudio N. Pasciullo, Erica Silver, Michael Joffe, Hadine TI Anxiety Predicts Reduction in Menopausal Vasomotor Symptoms with Hormonal and Non-Hormonal Treatments SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 19th Annual Meeting of the North-American-Menopause-Society CY SEP 24-27, 2008 CL Orlando, FL SP N Amer Menopause Soc C1 [Cohen, Lee S.; Pasciullo, Erica; Silver, Michael; Joffe, Hadine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Soares, Claudio N.] McMaster Univ, Hamilton, ON, Canada. 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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1228 EP 1228 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500155 ER PT J AU Kashino, SS Napolitano, DR Skobe, Z Campos-Neto, A AF Kashino, Suely S. Napolitano, Danielle R. Skobe, Ziedonis Campos-Neto, Antonio TI Guinea pig model of Mycobacterium tuberculosis latent/dormant infection SO MICROBES AND INFECTION LA English DT Article DE Latent infection; Dormant infection; Mycobacterium tuberculosis; Guinea pigs ID EXPERIMENTAL AIRBORNE TUBERCULOSIS; EXOGENOUS REINFECTION; TUBERCLE-BACILLI; MOUSE TISSUES; MORTALITY; PERSISTENCE; VACCINE AB Although guinea pigs are considered one of the best animal models of tuberculosis, little data exist describing latent or dormant tuberculosis infection in these animals. Here we address this issue using a streptomycin auxotrophic mutant of Mycobacterium tuberculosis. This mutant grows unimpaired in the presence of streptomycin but in its absence shifts to latency/dormancy (lack growth and over-expression of a-crystallin). To establish infection animals-are-inoculated with the mutant followed by daily administration of streptomycin (three weeks), which allows initial microbial multiplication in the animal's tissues. Withdrawal of streptomycin establishes latency/dormancy and few viable organisms are recovered from the animals' lungs and spleen six months later. During the infectious process guinea pigs steadily gained weight and presented no clinical signs (scuff fur and lethargy) of disease. Histopathology of organs mimicked tuberculous lesions in humans and PBMC from infected animals strongly responded to stimulation with PPD. Finally, tuberculin skin test (a hallmark of latent infection diagnosis) performed in infected animals was strongly positive (>= 15 mm induration). These results point to an interesting and reliable model of latent/dormant tuberculosis infection in guinea pigs. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [Kashino, Suely S.; Napolitano, Danielle R.; Skobe, Ziedonis; Campos-Neto, Antonio] Forsyth Inst, Dept Cytokine, Boston, MA USA. [Campos-Neto, Antonio] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. RP Campos-Neto, A (reprint author), Forsyth Inst, Dept Cytokine, Boston, MA USA. EM acampos@forsyth.org RI Kashino, Suely/F-4171-2012 FU National Institutes of Health [A1068291]; CAPES, Brazil [0783/05-6] FX Financial support: This work was supported in part by the following grant from the National Institutes of Health to ACN: A1068291. Dr. Napolitano was supported by a fellowship (process #0783/05-6) from CAPES, Brazil. NR 32 TC 17 Z9 18 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD NOV-DEC PY 2008 VL 10 IS 14-15 BP 1469 EP 1476 DI 10.1016/j.micinf.2008.08.010 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 388AD UT WOS:000261991800007 PM 18817888 ER PT J AU Wang, SA Tang, GL Fadare, O Hao, SY Raza, A Woda, BA Hasserjian, RP AF Wang, Sa A. Tang, Guilin Fadare, Oluwole Hao, Suyang Raza, Azra Woda, Bruce A. Hasserjian, Robert P. TI Erythroid-predominant myelodysplastic syndromes: enumeration of blasts from nonerythroid rather than total marrow cells provides superior risk stratification SO MODERN PATHOLOGY LA English DT Article DE myelodysplastic syndrome; erythroid precursors; blasts enumeration; prognosis; survival ID ACUTE MYELOID-LEUKEMIA; TRANS-RETINOIC ACID; GENE-EXPRESSION; BONE-MARROW; VALPROIC ACID; CD34(+) CELLS; CLASSIFICATION; ERYTHROLEUKEMIA; TRANSPLANTATION; PROPOSALS AB In the FAB (French-American-British) and WHO (World Heath Organization) classifications, the blasts in erythroleukemia (M6a) are enumerated from the marrow nonerythroid rather than the total-nucleated cells. However, the method for blast calculation in erythroid-predominant myelodysplastic syndrome (erythroblasts >= 50%) is not specified either in the FAB or WHO classifications. We retrieved the files of 74 erythroid-predominant myelodysplastic syndrome patients (17% of all myelodysplastic syndrome) and 192 myelodysplastic syndrome controls (erythroblasts < 50%). In erythroid-predominant myelodysplastic syndrome, by enumerating blasts from marrow nonerythroid cells rather than from total nucleated cells, 41 of 74 (55%) cases would be upgraded, either by disease subcategory or International Prognostic Scoring System. Importantly, the patients with >= 5% blasts demonstrated a superior survival to patients with >= 5% blasts (P = 0.002); this distinction was lost when blasts were calculated from total-nucleated cells. Of cases with >= 5% blasts, cytogenetics rather than blast count correlated with survival. We conclude that in erythroid-predominant myelodysplastic syndrome, blast calculation as a proportion of marrow nonerythroid rather than total nucleated cells can better stratify patients into prognostically relevant groups. C1 [Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Wang, Sa A.; Tang, Guilin; Hao, Suyang; Woda, Bruce A.] Univ Massachusetts, UMass Mem Med Ctr, Dept Pathol, Worcester, MA 01605 USA. [Fadare, Oluwole] Lackland AFB, Wilford Hall USAF Med Ctr, Dept Pathol, San Antonio, TX USA. [Raza, Azra] St Vincents Comprehens Canc Ctr, Myelodysplast Syndrome Program, New York, NY USA. [Hasserjian, Robert P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Wang, SA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd,Unit 72, Houston, TX 77030 USA. EM swang5@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 28 TC 31 Z9 31 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 2008 VL 21 IS 11 BP 1394 EP 1402 DI 10.1038/modpathol.2008.142 PG 9 WC Pathology SC Pathology GA 365RK UT WOS:000260425300013 PM 18839018 ER PT J AU Song, LL Alimirah, F Panchanathan, R Xin, H Choubeyt, D AF Song, Lynda Li Alimirah, Fatouma Panchanathan, Ravichandran Xin, Hong Choubeyt, Divaker TI Expression of an IFN-Inducible Cellular Senescence Gene, IFI16, Is Up-Regulated by p53 SO MOLECULAR CANCER RESEARCH LA English DT Article ID HUMAN FIBROBLASTS; POLYMORPHIC VARIANTS; DNA-DAMAGE; CANCER; CELLS; SUPPRESSOR; PATHWAY; PROTEIN; IFI-16; PROGRESSION AB IFN-inducible IFI16 protein (encoded by IFI16 gene at 1q23.1) is the human member of the IFN-inducible structurally related p200 family proteins. Increased expression of the IFI16 protein, a positive modulator of p53-mediated transcription, in normal old human diploid fibroblasts (HDF) is associated with cellular senescence-mediated cell growth arrest. However, the underlying mechanisms that contribute to transcriptional activation of the IFI16 gene in old HDFs remain to be elucidated. Here, we reported that functional activation of p53 in normal young HDFs and p53-null Saos2 cell line resulted in transcriptional activation of the IFI16 gene. We identified a potential p53 DNA-binding site (indicated as IFI16-p53-BS) in the 5'-regulatory region of the IFI16 gene. Importantly, p53 bound to IFI16-p53-BS in a sequence-specific manner in gel-mobility shift assays. Furthermore, p53 associated with the 5'-regulatory region of the IFI16 gene in chromatin immunoprecipitation assays. Interestingly, p53 associated with the regulatory region of the IFI16 gene only on treatment of cells with DNA-damaging agents or in the old, but not in the young, HDFs. Importantly, our promoter-reporter assays, which were coupled with site-directed mutagenesis of IFI16-p53-BS, showed that p53 activates transcription of the IFI16 gene in HDFs through the p53 DNA-binding site. Together, our observations provide support for the idea that up-regulation of IFI16 expression by p53 and functional interactions between IFI16 protein and p53 contribute to cellular senescence. (Mol Cancer Res 2008;6(11):1732-41) C1 [Song, Lynda Li; Panchanathan, Ravichandran; Choubeyt, Divaker] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Alimirah, Fatouma; Choubeyt, Divaker] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Panchanathan, Ravichandran; Xin, Hong; Choubeyt, Divaker] Loyola Univ Chicago, Maywood, IL USA. RP Choubeyt, D (reprint author), Univ Cincinnati, Dept Environm Hlth, 3223 Eden Ave,POB 670056, Cincinnati, OH 45267 USA. EM Divaker.choubeyt@uc.edu RI Panchanathan, Ravichandran/E-1801-2015 FU NIA NIH HHS [AG025036] NR 41 TC 23 Z9 24 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2008 VL 6 IS 11 BP 1732 EP 1741 DI 10.1158/1541-7786.MCR-08-0208 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 375SV UT WOS:000261134500008 PM 18974396 ER PT J AU Hingtgen, S Ren, XH Terwilliger, E Masson, M Weissleder, R Shah, K AF Hingtgen, Shawn Ren, Xianghui Terwilliger, Ernie Masson, Marie Weissleder, Ralph Shah, Khalid TI Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID APOPTOSIS-INDUCING LIGAND; IN-VIVO; MALIGNANT GLIOMA; TUMOR-THERAPY; CANCER-THERAPY; BRAIN-TUMORS; GENE-THERAPY; APO2L/TRAIL; REGRESSION; EXPRESSION AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells. However, its short half-life, poor delivery, and TRAIL-resistant tumor cells have diminished its clinical efficacy. In this study, we explored whether novel delivery methods will represent new and effective ways to treat gliomas and if adjuvant therapy with the chemotherapeutic agent temozolomide would enhance the cytotoxic properties of TRAIL in glioma lines resistant to TRAIL monotherapy. We have engineered adeno-associated virus (AAV) vectors encoding recombinant secreted TRAIL (S-TRAIL) and bioluminescent-fluorescent marker fusion proteins and show that AAV-delivered S-TRAIL leads to varying degrees of killing in multiple glioma lines, which correspond with caspase-3/7 activation. In vivo, dual bioluminescent imaging revealed efficient delivery of therapeutic AAV vectors directly into the tumor mass, which induced marked attenuation of tumor progression. Treatment of glioma cells with the chemotherapeutic agent temozolomide alone lead to a significant accumulation of cells in G(2)-M phase, activated the cell cycle checkpoint protein Chk1, and increased death receptor expression in a time-dependent manner. Furthermore, combined treatment with AAV-S-TRAIL or neural stem cell-S-TRAIL and temozolomide induced cell killing and markedly up-regulated proapoptotic proteins in glioma cells least sensitive to TRAIL. This study elucidates novel means of delivering S-TRAIL to gliomas and suggests combination of clinically relevant temozolomide and S-TRAIL may represent a new therapeutic option with increased potency for glioblastoma patients. [Mol Cancer Ther 2008;7(11):3575-85] C1 [Hingtgen, Shawn; Weissleder, Ralph; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Charlestown, MA 02129 USA. [Hingtgen, Shawn; Weissleder, Ralph; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, Charlestown, MA 02129 USA. [Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Masson, Marie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Charlestown, MA 02129 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Syst Biol,Ctr Syst Biol, Charlestown, MA 02129 USA. [Ren, Xianghui; Terwilliger, Ernie] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Harvard Inst Med,Div Expt Med, Boston, MA USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Room 5421,Bldg 149,13th St, Charlestown, MA 02129 USA. EM kshah@helix.mgh.harvard.edu FU NIH [T32 CA79443]; American Brain Tumor Association; Goldhirsh Foundation; Catherine and Pappas award in Neuro-oncology; American cancer Gene Therapy (ACGT) FX NIH grant T32 CA79443 (R. Weissleder) and American Brain Tumor Association, Goldhirsh Foundation, Catherine and Pappas award in Neuro-oncology, and American cancer Gene Therapy (ACGT) (K. Shah). NR 49 TC 37 Z9 38 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2008 VL 7 IS 11 BP 3575 EP 3585 DI 10.1158/1535-7163.MCT-08-0640 PG 11 WC Oncology SC Oncology GA 377ZC UT WOS:000261289900013 PM 19001440 ER PT J AU Krum, SA Miranda-Carboni, GA Lupien, M Eeckhoute, J Carroll, JS Brown, M AF Krum, Susan A. Miranda-Carboni, Gustavo A. Lupien, Mathieu Eeckhoute, Jerome Carroll, Jason S. Brown, Myles TI Unique ER alpha Cistromes Control Cell Type-Specific Gene Regulation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; BREAST-CANCER; OSTEOBLAST DIFFERENTIATION; ALKALINE-PHOSPHATASE; ANTIGEN PROMOTER; BONE-FORMATION; BINDING-SITES; HIGH-AFFINITY; TARGET GENE; CYCLIN D1 AB Estrogens play an important role in normal physiology and in a variety of pathological states involving diverse tissues including breast and bone. The mechanism by which estrogens exert cell type- and disease-specific effects, however, remains to be explained. We have compared the gene expression profile of the MCF7 breast cancer cell line with that of the osteoblast-like cell line U2OS-ER alpha by expression microarrays. We find that fewer than 10% of the 17 beta-estradiol (E2)-regulated genes are common to both cell types. We have validated this in primary calvarial osteoblasts. To dissect the mechanism underlying the cell type- specific E2 regulation of gene expression in MCF7 and U2OS-ER alpha cells, we compared the ER alpha binding sites on DNA in the two cell types by performing chromatin immunoprecipitation (ChIP) on genomic tiling arrays (ChIP-on-chip). Consistent with the distinct patterns of E2-regulated gene expression in these two cell lines, we find that the vast majority of ER alpha binding sites are also cell type specific and correlate both in position and number with cell type-specific gene regulation. Interestingly, although the forkhead factor FoxA1 plays a critical role in defining the ER alpha cistrome in MCF7 cells, it is not expressed in U2OS-ER alpha cells, and forkhead motifs are not enriched in the ER alpha cistrome in these cells. Finally, the ER alpha cistromes are correlated with cell type- specific epigenetic histone modifications. These results support a model for the cell type-specific action of E2 being driven primarily through specific ER alpha occupancy of epigenetically marked cis-regulatory regions of target genes. (Molecular Endocrinology 22: 2393-2406, 2008) C1 [Krum, Susan A.; Lupien, Mathieu; Eeckhoute, Jerome; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. [Miranda-Carboni, Gustavo A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Miranda-Carboni, Gustavo A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Carroll, Jason S.] Cambridge Res Inst, Canc Res UK, Cambridge CB2 0RE, England. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, 44 Binney St,D730, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI krum, susan/D-7282-2013; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [P01 CA8011105]; NIDDK NIH HHS [R01DK074967, R01 DK074967] NR 51 TC 84 Z9 85 U1 0 U2 5 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 NOV PY 2008 VL 22 IS 11 BP 2393 EP 2406 DI 10.1210/me.2008-0100 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365SZ UT WOS:000260429400003 PM 18818283 ER PT J AU Agoulnik, IU Bingman, WE Nakka, M Li, W Wang, QB Liu, XS Brown, M Weigel, NL AF Agoulnik, Irina U. Bingman, William E., III Nakka, Manjula Li, Wei Wang, Qianben Liu, X. Shirley Brown, Myles Weigel, Nancy L. TI Target Gene-Specific Regulation of Androgen Receptor Activity by p42/p44 Mitogen-Activated Protein Kinase SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROSTATE-CANCER CELLS; LIGAND-INDEPENDENT ACTIVATION; PROGESTERONE-RECEPTOR; PHOSPHORYLATION SITES; SIGNALING PATHWAY; TRANSCRIPTION; GROWTH; PROLIFERATION; BINDING; IDENTIFICATION AB Evidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation therapies, highlights the need to find alternate means to block AR activity. AR, a hormone-activated transcription factor, and its coactivators are phosphoproteins. Thus, we sought to determine whether inhibition of specific cell signaling pathways would reduce AR function. We found that short-term inhibition of p42/p44 MAPK activity either by a MAPK kinase inhibitor, U0126, or by depletion of kinase with small interfering RNA caused target gene-specific reductions in AR activity. AR enhances histone H3 acetylation of target genes that are sensitive to U0126 including prostate-specific antigen and TMPRSS2, but does not increase histone H3 acetylation of the U0126-resistant PMEPA1 gene. Thus, although AR induces transcription of many target genes, the molecular changes induced by AR at the chromatin level are target gene specific. Long-term treatment (24-48 h) with U0126 causes a G 1 cell cycle arrest and reduces AR expression both through a decrease in AR mRNA and a reduction in AR protein stability. Thus, treatments that reduce p42/p44 MAPK activity in prostate cancer have the potential to reduce AR activity through a reduction in expression levels as well as by target gene-selective inhibition of AR function. (Molecular Endocrinology 22: 2420-2432, 2008) C1 [Agoulnik, Irina U.; Bingman, William E., III; Nakka, Manjula; Li, Wei; Weigel, Nancy L.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Li, Wei] Baylor Coll Med, Duncan Canc Ctr, Houston, TX 77030 USA. [Weigel, Nancy L.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Wang, Qianben; Brown, Myles] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Weigel, NL (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM nweigel@bcm.tmc.edu RI Li, Wei/A-8544-2009; Wang, Qianben/E-4267-2011; OI Brown, Myles/0000-0002-8213-1658; Agoulnik, Irina/0000-0003-4889-0324 FU National Institutes of Health (NIH) [DK65262, CA58204, T32DK07696] FX This work was supported by National Institutes of Health (NIH) Grant DK65262 (to N.L.W. and I.U.A.); NIH Grant CA58204, the Specialized Program in Research Excellence in Prostate Cancer (to I.U.A. and N.L.W.); and NIH Grant T32DK07696 (to M.N.). NR 46 TC 25 Z9 26 U1 0 U2 3 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 NOV PY 2008 VL 22 IS 11 BP 2420 EP 2432 DI 10.1210/me.2007-0481 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365SZ UT WOS:000260429400005 PM 18787043 ER PT J AU Khan, N Mupparaju, SP Mintzopoulos, D Kesarwani, M Righi, V Rahme, LG Swartz, HM Tzika, AA AF Khan, Nadeem Mupparaju, Sriram P. Mintzopoulos, Dionyssios Kesarwani, Meenu Righi, Valeria Rahme, Laurence G. Swartz, Harold M. Tzika, A. Aria TI Burn trauma in skeletal muscle results in oxidative stress as assessed by in vivo electron paramagnetic resonance SO MOLECULAR MEDICINE REPORTS LA English DT Article DE electron paramagnetic resonance; oximetry; partial pressure of oxygen; redox; skeletal muscle; burn; trauma; mitochondria; reactive oxygen species; nuclear magnetic resonance; genomics ID INTRAMYOCELLULAR LIPID CONCENTRATIONS; CLINICAL-APPLICATIONS; INSULIN SENSITIVITY; EPR SPECTROSCOPY; MITOCHONDRIAL; OXIMETRY; INJURY; MOUSE; TISSUE; COACTIVATORS AB Using a mouse model, we tested the hypotheses that severe burn trauma causes metabolic disturbances in skeletal muscle, and that these can be measured and repeatedly followed by in vivo electron paramagnetic resonance (EPR). We used a 1.2-GHz (L-band) EPR spectrometer to measure partial pressure of oxygen (pO(2)) levels, redox status and oxidative stress following a non-lethal burn trauma model to the left hind limbs of mice. Results obtained in the burned mouse gastrocnemius muscle indicated a significant decrease in tissue pO(2) immediately (P=0.032) and at 6 h post burn (P=0.004), compared to the gastrocnemius of the unburned hind limb. The redox status of the skeletal muscle also peaked at 6 h post burn (P=0.027) in burned mice. In addition, there was an increase in the EPR signal of the nitroxide produced by oxidation of the hydroxylamine (CP-H) probe at 12 h post burn injury, indicating a burn-induced increase in mitochondrial reactive oxygen species (ROS). The nitroxide signal continued to increase between 12 and 24 h, suggesting a further increase in ROS generation post burn. These results confirm genomic results, which indicate a downregulation of antioxidant genes and therefore strongly suggest the dysfunction of the mitochondrial oxidative system. We believe that the direct measurement of tissue parameters such as pO(2), redox and ROS by EPR may be used to complement measurements by nuclear magnetic resonance (NMR) in order to assess tissue damage and the therapeutic effectiveness of antioxidant agents in severe burn trauma. C1 [Mintzopoulos, Dionyssios; Righi, Valeria; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. [Khan, Nadeem; Mupparaju, Sriram P.; Swartz, Harold M.] EPR Ctr Viable Syst, Dept Diagnost Radiol, Dartmouth Med Sch, Hanover, NH 03755 USA. [Mintzopoulos, Dionyssios; Righi, Valeria; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02114 USA. [Kesarwani, Meenu; Rahme, Laurence G.; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Mol Surg Lab, Boston, MA 02114 USA. [Mintzopoulos, Dionyssios; Kesarwani, Meenu; Rahme, Laurence G.; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu OI Righi, Valeria/0000-0003-2394-8462 FU Shriners Hospital for Children [8893]; National Institutes of Health (NIH) [P50GM021700]; National Institute of Diabetes and Digest and Kidney (NIDDK) [DK072112] FX This work was supported in part by a Shriners Hospital for Children research grant no. 8893 to A. Aria Tzika, a National Institutes of Health (NIH) Center Grant P50GM021700 (Ronald G. Tompkins, PI; A. Aria Tzika, Director of NMR Core), and by a National Institute of Diabetes and Digest and Kidney (NIDDK) research grant no. DK072112 to Nadeem Khan. We thank Dr Huagang Hou, Dartmouth Medical School, for advice on the procedures for EPR measurements. We also thank Drs Katie Edmondson and Ann Power Smith of Write Science Right for editorial assistance. NR 48 TC 9 Z9 9 U1 1 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1791-2997 EI 1791-3004 J9 MOL MED REP JI Mol. Med. Rep. PD NOV-DEC PY 2008 VL 1 IS 6 BP 813 EP 819 DI 10.3892/mmr_00000033 PG 7 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA 374QH UT WOS:000261058300007 PM 21179378 ER PT J AU Ohtsuka, T Mitsuno, M Kitajima, Y Ide, T Lee, SW Miyazaki, K AF Ohtsuka, Takao Mitsuno, Mayumi Kitajima, Yoshihiko Ide, Takao Lee, Sam W. Miyazaki, Kohji TI Role of ASC in hypoxia-mediated cell death in pancreatic cancer SO MOLECULAR MEDICINE REPORTS LA English DT Article DE hypoxia; pancreatic cancer; ASC ID TUMOR-GROWTH; APOPTOSIS; P53; GEMCITABINE; ACTIVATION; HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA; CHEMOSENSITIVITY; CHEMORESISTANCE; PROGRESSION; EXPRESSION AB ASC, an apoptosis-associated speck-like protein, can regulate apoptosis in response to various types of cell death stimuli. In this study, we investigated the role of ASC in hypoxia-mediated cell death in pancreatic cancer. ASC was inducible under a 1% O(2) hypoxic condition in pancreatic cancer cells, which was HIF1 alpha-dependent but p53-independent. Two representative chemotherapeutic agents for pancreatic cancer, 5-fluorouracil and gemcitabine, promoted cell death in a p53-dependent manner; however, 1% hypoxia caused chemoresistance to these drugs. Western blot analysis of this condition showed that expression of Bax, a pro-apoptotic gene, decreased, while the anti-apoptotic genes IAP-2 and survivin increased. These results suggest that, although hypoxia induces both pro-apoptotic and anti-apoptotic genes, the total balance seems to be anti-apoptotic dominant, which might explain chemoresistance in pancreatic cancer. To overcome this antiapoptotic dominant condition, we infected adenovirus-expressing ASC into pancreatic cancer cells. The expressed ASC induced cell death even under 20% normoxia, and was enhanced by hypoxia. Our data demonstrate the possible mechanism of chemoresistance under hypoxia in pancreatic cancer cells, thereby suggesting the potential use of ASC as a new treatment strategy for pancreatic cancer. C1 [Ohtsuka, Takao; Mitsuno, Mayumi; Kitajima, Yoshihiko; Ide, Takao; Miyazaki, Kohji] Saga Univ, Fac Med, Dept Surg, Saga 8498501, Japan. [Ide, Takao; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Ide, Takao; Lee, Sam W.] Harvard Univ, Sch Med, Boston, MA USA. RP Ohtsuka, T (reprint author), Saga Univ, Fac Med, Dept Surg, 5-1-1 Nabeshima, Saga 8498501, Japan. EM ootsuka4@cc.saga-u.ac.jp FU Ministry of Education, Science, Sports, and Culture of Japan [19790943] FX This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (no. 19790943). NR 24 TC 1 Z9 1 U1 1 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1791-2997 J9 MOL MED REP JI Mol. Med. Rep. PD NOV-DEC PY 2008 VL 1 IS 6 BP 827 EP 831 DI 10.3892/mmr_00000035 PG 5 WC Pathology SC Pathology GA 374QH UT WOS:000261058300009 PM 21479491 ER PT J AU Dracheva, S Patel, N Woo, DA Marcus, SM Siever, LJ Haroutunian, V AF Dracheva, S. Patel, N. Woo, D. A. Marcus, S. M. Siever, L. J. Haroutunian, V. TI Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide SO MOLECULAR PSYCHIATRY LA English DT Article DE suicide; bipolar disorder; schizophrenia; RNA editing; ADAR; prefrontal cortex ID 5-HT2C RECEPTOR; MENTAL-DISORDERS; GENE FAMILY; BEHAVIOR; TRANSPORTER; EXPRESSION; PROTEIN; NEUROBIOLOGY; ASSOCIATION; MECHANISMS AB Suicide is a major public health problem with similar to 1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT(2C)R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT(2C)R mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT(2C)R, that is, VSV (Val156-Ser158-Val160). Because the VSV isoform of 5-HT(2C)R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior. C1 [Dracheva, S.; Patel, N.; Woo, D. A.; Marcus, S. M.; Siever, L. J.; Haroutunian, V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Dracheva, S.; Marcus, S. M.; Siever, L. J.; Haroutunian, V.] James J Peters Vet Affairs Med Ctr, MIRECC, Bronx, NY USA. RP Dracheva, S (reprint author), Bronx VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM stella.dracheva@mssm.edu FU VA Merit; VISN3 Mental Illness Research; Education Clinical Center (MIRECC) FX Postmortem brain tissue was donated by The Stanley Medical Research Institute's array collection courtesy of Drs Michael B Knable, E Fuller Torrey, Maree J Webster and Robert H Yolken. This study was supported by VA Merit award to SD and by the VISN3 Mental Illness Research and Education Clinical Center (MIRECC) (LJS, VH and SD). We thank Dr William M Byne for his help in the preparation of the article. NR 51 TC 43 Z9 44 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2008 VL 13 IS 11 BP 1001 EP 1010 DI 10.1038/sj.mp.4002081 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 368OS UT WOS:000260632200003 PM 17848916 ER PT J AU de Chassey, B Navratil, V Tafforeau, L Hiet, MS Aublin-Gex, A Agaugue, S Meiffren, G Pradezynski, F Faria, BF Chantier, T Le Breton, M Pellet, J Davoust, N Mangeot, PE Chaboud, A Penin, F Jacob, Y Vidalain, PO Vidal, M Andre, P Rabourdin-Combe, C Lotteau, V AF de Chassey, B. Navratil, V. Tafforeau, L. Hiet, M. S. Aublin-Gex, A. Agaugue, S. Meiffren, G. Pradezynski, F. Faria, B. F. Chantier, T. Le Breton, M. Pellet, J. Davoust, N. Mangeot, P. E. Chaboud, A. Penin, F. Jacob, Y. Vidalain, P. O. Vidal, M. Andre, P. Rabourdin-Combe, C. Lotteau, V. TI Hepatitis C virus infection protein network SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE Functional analysis; hepatitis C; interactome; virus-host cell ID INSULIN-RECEPTOR SUBSTRATE-1; LIVER FIBROSIS; INTERACTING PROTEINS; INTERACTION DATASETS; CORE PROTEIN; FACTOR YY1; RESISTANCE; DATABASE; YEAST; REPLICATION AB A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein-protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGF beta pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins. C1 [de Chassey, B.; Tafforeau, L.; Hiet, M. S.; Aublin-Gex, A.; Agaugue, S.; Meiffren, G.; Pradezynski, F.; Faria, B. F.; Chantier, T.; Le Breton, M.; Pellet, J.; Davoust, N.; Mangeot, P. E.; Andre, P.; Rabourdin-Combe, C.; Lotteau, V.] INSERM, U851, IMAP Team, F-69007 Lyon, France. [de Chassey, B.; Navratil, V.; Tafforeau, L.; Hiet, M. S.; Aublin-Gex, A.; Agaugue, S.; Meiffren, G.; Pradezynski, F.; Faria, B. F.; Chantier, T.; Le Breton, M.; Pellet, J.; Davoust, N.; Mangeot, P. E.; Chaboud, A.; Penin, F.; Andre, P.; Rabourdin-Combe, C.; Lotteau, V.] Univ Lyon, BioSci Lyon Gerland IFR128, Lyon, France. [Navratil, V.] INRA, UMR 754, Lyon, France. [Chaboud, A.; Penin, F.] CNRS, UMR 5086, Inst Biol & Chim Prot, Lyon, France. [Jacob, Y.] Inst Pasteur, Unite Postulante Genet Papillomavirus & Canc Huma, Paris, France. [Vidalain, P. O.] Inst Pasteur, CNRS, URA 3015, Lab Genom Virale & Vaccinat, Paris, France. [Vidal, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Andre, P.; Lotteau, V.] Hop Croix Rousse, Hosp Civils Lyon, Virol Lab, F-69317 Lyon, France. RP Lotteau, V (reprint author), INSERM, U851, IMAP Team, 21 Av T Garnier, F-69007 Lyon, France. EM vincent.lotteau@inserm.fr RI navratil, vincent/C-4193-2008; lotteau, vincent/M-8143-2014; OI Tafforeau, Lionel/0000-0002-8468-7422 FU ANRS; INSERM; French Ministry of Industry; INRA FX This work was funded by ANRS, INSERM and the French Ministry of Industry. We acknowledge L Meyniel for critical reading of the manuscript. We also acknowledge Lyon Biopole. V Navratil is supported by a grant from INRA. NR 66 TC 213 Z9 216 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD NOV PY 2008 VL 4 AR 230 DI 10.1038/msb.2008.66 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 379KG UT WOS:000261394500005 PM 18985028 ER PT J AU Peterson, RT AF Peterson, Randall T. TI Chemical biology and the limits of reductionism SO NATURE CHEMICAL BIOLOGY LA English DT Editorial Material ID SMALL-MOLECULE LIBRARIES; INHIBITORS; ZEBRAFISH; ASSAYS; TARGETS; GENES AB Chemical biology and systems biology have grown and evolved in parallel during the past decade, but the mindsets of the two disciplines remain quite different. As the inevitable intersections between the disciplines become more frequent, chemical biology has an opportunity to assimilate the most powerful ideas from systems biology. Can the integrationist mindset of systems biology liberate chemical biology from the compulsion to reduce everything to individual small molecule-target pairings? C1 [Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02139 USA. [Peterson, Randall T.] MIT, Broad Inst, Cambridge, MA 02142 USA. RP Peterson, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02139 USA. EM peterson@cvrc.mgh.harvard.edu NR 20 TC 33 Z9 35 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD NOV PY 2008 VL 4 IS 11 BP 635 EP 638 DI 10.1038/nchembio1108-635 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 364CY UT WOS:000260315000002 PM 18936741 ER PT J AU Swearingen, B Loeffler, J AF Swearingen, Brooke Loeffler, Jay TI Does radiosurgery have a role in the treatment of acromegaly? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE acromegaly; pituitary; radiosurgery; remission; tumor ID GROWTH-HORMONE; RADIOTHERAPY AB Surgical treatment of acromegaly aims to normalize the levels of growth hormone and insulin-like growth factor I (IGF-I) and to control tumor growth; however, not all patients achieve remission. Treatment of residual tumor or recurrent disease, therefore, requires additional modalities, such as somatostatin analogs or radiosurgery. Losa et al. have evaluated the efficacy and safety of radiosurgery in a cohort of 83 patients with acromegaly who had previously undergone surgical debulking. The authors reported a 5-year biochemical remission rate of 52.6% after treatment. Remission was found to correlate with the baseline growth hormone and IGF-I levels, but not with tumor volume. In this Practice Point commentary, we place the findings of Losa et al. into clinical context, discuss the possible limitations of their approach, and comment on the relevance of radiosurgery to the treatment of acromegaly. C1 [Swearingen, Brooke] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Swearingen, Brooke; Loeffler, Jay] Harvard Univ, Sch Med, Boston, MA USA. RP Swearingen, B (reprint author), Massachusetts Gen Hosp, ACC 331,15 Parkman St, Boston, MA 02114 USA. EM bswearingen@partners.org NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD NOV PY 2008 VL 4 IS 11 BP 592 EP 593 DI 10.1038/ncpendmet0948 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 361YX UT WOS:000260165700003 PM 18762791 ER PT J AU Lo, J AF Lo, Janet TI Does growth hormone therapy benefit body composition and glucose homeostasis in girls with Turner syndrome? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE fat distribution; growth hormone; impaired glucose tolerance; insulin; Turner syndrome AB Growth hormone therapy is commonly used in girls with Turner syndrome to improve short stature associated with the disease. Concerns have been raised, however, regarding the effect of growth hormone on glucose metabolism. In this Practice Point commentary, I discuss the findings of a cross-sectional study performed by Wooten et al. that evaluated growth hormone treatment in girls with Turner syndrome. The authors found that girls with Turner syndrome who received growth hormone treatment had a lower BMI, less intra-abdominal fat, less subcutaneous abdominal fat, and less total body fat than girls with Turner syndrome who never received growth hormone. Importantly, girls who were treated with growth hormone were less likely to have impaired glucose tolerance than girls who never received growth hormone. Although the results of this study are supportive of the long-term benefits of growth hormone treatment in girls with Turner syndrome, interpretation of these findings should also take into account the limitation that this study was not randomized. C1 [Lo, Janet] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, Boston, MA 02114 USA. [Lo, Janet] Harvard Univ, Sch Med, Boston, MA USA. [Lo, Janet] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. RP Lo, J (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM jlo@partners.org NR 7 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD NOV PY 2008 VL 4 IS 11 BP 596 EP 597 DI 10.1038/ncpendmet0954 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 361YX UT WOS:000260165700005 PM 18725904 ER PT J AU Sorensen, AG Batchelor, TT Wen, P Zhang, WT Jain, RK AF Sorensen, A. Gregory Batchelor, Tracy T. Wen, PatrickY Zhang, Wei-Ting Jain, Rakesh K. TI Response criteria for glioma SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE blood-brain barrier; criteria; glioma; MRI; RECIST ID HIGH-GRADE GLIOMAS; RECURRENT MALIGNANT GLIOMA; SURROGATE END-POINTS; PHASE-II; RADIATION NECROSIS; TUMOR; CHEMOTHERAPY; BEVACIZUMAB; BRAIN; VOLUME AB The current method for assessing the response to therapy of glial tumors was described by Macdonald et al. in 1990. Under this paradigm, response categorization is determined on the basis of changes in the cross-sectional area of a tumor on neuroimaging, coupled with clinical assessment of neurological status and corticosteroid utilization. These categories of response have certain limitations; for example, cross-sectional assessment is not as accurate as volumetric assessment, which is now feasible. Disentangling antitumor effects of therapies from their effects on blood-brain barrier permeability can be challenging. The use of insufficient response criteria might be overestimating the true benefits of drugs in early-stage studies, and, therefore, such therapies could mistakenly move forward into later phases, only to result in disappointment when overall survival is measured. We propose that studies report both radiographic and clinical response rates, use volumetric rather than cross-sectional area to measure lesion size, and incorporate findings from mechanistic imaging and blood biomarker studies more frequently, and also suggest that investigators recognize the limitations of imaging biomarkers as surrogate end points. C1 [Jain, Rakesh K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab Tumor Biol, Cambridge, MA 02138 USA. [Sorensen, A. Gregory] MIT, Cambridge, MA 02139 USA. [Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Wen, PatrickY] Dana Farber Brigham & Womens Hosp, Ctr Neurooncol, Boston, MA USA. RP Sorensen, AG (reprint author), Mailcode 149-2301,Bldg 149,13th St, Boston, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu FU US Public Health Service [M01-RR-01066, 1R21CA117079-01, 5T32CA009502-20, 5P41RR014075, 5P01CA080124]; MIND Institute FX This work was funded by the US Public Health Service (grants M01-RR-01066, 1R21CA117079-01, 5T32CA009502-20, 5P41RR014075 and 5P01CA080124) and The MIND Institute. We wish to thank Craig Peterson for technical assistance, and Zariana Nikolova, Richard Parker, Wendy Hayes, and Steven Green for helpful discussions. NR 32 TC 107 Z9 109 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2008 VL 5 IS 11 BP 634 EP 644 DI 10.1038/ncponc1204 PG 11 WC Oncology SC Oncology GA 366FO UT WOS:000260466200006 PM 18711427 ER PT J AU Hurwitz, MD AF Hurwitz, Mark D. TI Technology Insight: combined external-beam radiation therapy and brachytherapy in the management of prostate cancer SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE brachytherapy; combined-modality therapy (CMT); external-beam radiation therapy (EBRT); prostate cancer ID DOSE-RATE BRACHYTHERAPY; QUALITY-OF-LIFE; AMERICAN-BRACHYTHERAPY; PHASE-II; INTERSTITIAL BRACHYTHERAPY; GASTROINTESTINAL TOXICITY; SOCIETY RECOMMENDATIONS; CONFORMAL RADIATION; MORBIDITY OUTCOMES; PERMANENT IMPLANT AB External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity. C1 Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol,Reg Program Dev, Boston, MA 02115 USA. RP Hurwitz, MD (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol,Reg Program Dev, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM mhurwitz@lroc.harvard.edu NR 54 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 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2008 VL 5 IS 11 BP 668 EP 676 DI 10.1038/ncponc1224 PG 9 WC Oncology SC Oncology GA 366FO UT WOS:000260466200009 PM 18825143 ER PT J AU Morgan, BA AF Morgan, Bruce A. TI A glorious revolution in stem cell biology SO NATURE GENETICS LA English DT Editorial Material ID EPIDERMIS AB A newly described Lgr5-expressing cell population is poised to depose the reigning monarch of the follicular hierarchy, the label-retaining cell, to claim the title as stem cell of the hair follicle. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu NR 8 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2008 VL 40 IS 11 BP 1269 EP 1270 DI 10.1038/ng1108-1269 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 366RQ UT WOS:000260501500006 PM 18957980 ER PT J AU Petrocca, F Lieberman, J AF Petrocca, Fabio Lieberman, Judy TI RIG-ing an antitumor response SO NATURE MEDICINE LA English DT Editorial Material ID SIRNA; RNA AB A small interfering RNA has been engineered to silence an oncogene and activate the immune response simultaneously. The approach shrinks tumors in mice (pages 1256-1263). C1 [Petrocca, Fabio] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Petrocca, F (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 NR 8 TC 5 Z9 5 U1 0 U2 1 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 NOV PY 2008 VL 14 IS 11 BP 1152 EP 1153 DI 10.1038/nm1108-1152 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 370GR UT WOS:000260751200014 PM 18989278 ER PT J AU Liu, WZ Kennington, LA Rosas, HD Hersch, S Cha, JH Zamore, PD Aronin, N AF Liu, Wanzhao Kennington, Lori A. Rosas, H. Diana Hersch, Steven Cha, Jang-Ho Zamore, Phillip D. Aronin, Neil TI Linking SNPs to CAG repeat length in Huntington's disease patients SO NATURE METHODS LA English DT Article ID TRINUCLEOTIDE REPEAT; MUTANT HUNTINGTIN; GENE HOMOLOG; ALLELE; INACTIVATION; SIRNA AB Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples. C1 [Zamore, Phillip D.] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA. [Zamore, Phillip D.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. [Liu, Wanzhao; Kennington, Lori A.; Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Rosas, H. Diana; Hersch, Steven; Cha, Jang-Ho] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Zamore, PD (reprint author), Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, 364 Plantat St, Worcester, MA 01605 USA. EM phillip.zamore@umassmed.edu; neil.aronin@umassmed.edu RI Zamore, Phillip/A-8941-2013 FU NIH Diabetes and Endocrinology Research [5P30DK32520-25]; US National Institutes of Health [NS38194, 1P01NS058793]; National Institute of Neurological Disorders and Stroke [NS042861]; CHDI, Inc. FX We thank M. Chan for advice on lymphocyte isolation and culture, J. Straubhauer (NIH Diabetes and Endocrinology Research grant 5P30DK32520-25) for assistance with data analysis, members of Zamore and Aronin labs for helpful discussions, assistance and comments on the manuscript. US National Institutes of Health (NS38194 to N. A., P.D.Z. and M. DiFiglia; 1P01NS058793 to H. D. R. and S. H.; and National Institute of Neurological Disorders and Stroke NS042861 to H.D.R.) and CHDI, Inc. (N. A. and P.D.Z.) supported this work. NR 15 TC 22 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD NOV PY 2008 VL 5 IS 11 BP 951 EP 953 DI 10.1038/nmeth.1261 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 367DK UT WOS:000260532500014 PM 18931668 ER PT J AU Lundstrom, BN Higgs, MH Spain, WJ Fairhall, AL AF Lundstrom, Brian N. Higgs, Matthew H. Spain, William J. Fairhall, Adrienne L. TI Fractional differentiation by neocortical pyramidal neurons SO NATURE NEUROSCIENCE LA English DT Article ID SPIKE-FREQUENCY ADAPTATION; SENSORY ADAPTATION; NEURAL CODE; CORTICAL-NEURONS; ORDER DYNAMICS; BARREL CORTEX; BRAIN-STEM; POWER-LAW; IN-VITRO; MECHANISMS AB Neural systems adapt to changes in stimulus statistics. However, it is not known how stimuli with complex temporal dynamics drive the dynamics of adaptation and the resulting firing rate. For single neurons, it has often been assumed that adaptation has a single time scale. We found that single rat neocortical pyramidal neurons adapt with a time scale that depends on the time scale of changes in stimulus statistics. This multiple time scale adaptation is consistent with fractional order differentiation, such that the neuron's firing rate is a fractional derivative of slowly varying stimulus parameters. Biophysically, even though neuronal fractional differentiation effectively yields adaptation with many time scales, we found that its implementation required only a few properly balanced known adaptive mechanisms. Fractional differentiation provides single neurons with a fundamental and general computation that can contribute to efficient information processing, stimulus anticipation and frequency-independent phase shifts of oscillatory neuronal firing. C1 [Lundstrom, Brian N.; Higgs, Matthew H.; Spain, William J.; Fairhall, Adrienne L.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Higgs, Matthew H.; Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98108 USA. RP Fairhall, AL (reprint author), Univ Washington, Dept Physiol & Biophys, Box 357290, Seattle, WA 98195 USA. EM fairhall@u.washington.edu FU Burroughs-Wellcome Careers at the Scientific Interface grant; McKnight Scholar Award; Sloan Research Fellowship; National Institute of Neurological Disorders and Stroke [F30NS055650]; University of Washington's Medical Scientist Training Program; Achievement Rewards for College Scientists (ARCS) fellowship; Veterans Affairs Merit Review FX We are grateful to B. Aguera y Arcas, W. Bialek, F. Dunn, M. Famulare, M. Giugliano, S. Hong, M. Maravall, P. Murphy, F. Rieke, L. Sorensen and B. Wark for helpful discussions and/or comments on the manuscript. We thank S. Usher for excellent technical assistance. This work was supported by a Burroughs-Wellcome Careers at the Scientific Interface grant, and a McKnight Scholar Award and a Sloan Research Fellowship to A.L.F.B.N.L. was supported by grant number F30NS055650 from the National Institute of Neurological Disorders and Stroke, the University of Washington's Medical Scientist Training Program (supported by the National Institute of General Medical Sciences), and an Achievement Rewards for College Scientists (ARCS) fellowship. M. H. H. and W.J.S. were supported by a Veterans Affairs Merit Review to W.J.S. NR 50 TC 171 Z9 173 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2008 VL 11 IS 11 BP 1335 EP 1342 DI 10.1038/nn.2212 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 366HZ UT WOS:000260472700023 PM 18931665 ER PT J AU Kaelin, WG AF Kaelin, William G., Jr. TI The von Hippel-Lindau tumour suppressor protein: O-2 sensing and cancer SO NATURE REVIEWS CANCER LA English DT Review ID HYPOXIA-INDUCIBLE-FACTOR; RENAL-CELL-CARCINOMA; HYDROXYLASE DOMAIN PROTEIN-2; RNA-POLYMERASE-II; PROLYL HYDROXYLASE; FACTOR-ALPHA; GENE-PRODUCT; HIF-ALPHA; PROLINE HYDROXYLATION; VASCULAR TUMORS AB The von Hippel-Lindau disease is caused by inactivating germline mutations of the VHL tumour suppressor gene and is associated with an increased risk of a variety of tumours in an allele-specific manner. The role of the heterodimeric transcription factor hypoxia-inducible factor (HIF) in the pathogenesis of VHL-defective tumours has been more firmly established during the past 5 years. In addition, there is now a greater appreciation of HIF-independent VHL functions that are relevant to tumour development, including maintenance of the primary cilium, regulation of extracellular matrix formation and turnover, and modulation of cell death in certain cell types following growth factor withdrawal or in response to other forms of stress. C1 [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Kaelin, William G., Jr.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM William_Kaelin@dfci.harvard.edu FU Doris Duke Charitable Foundation; National Institutes of Health; Howard Hughes Medical Institute; Breast Cancer Research Foundation FX W. G. K. is supported by the Doris Duke Charitable Foundation as a Distinguished Clinical Scientist and by the National Institutes of Health, the Howard Hughes Medical Institute and the Breast Cancer Research Foundation. NR 145 TC 328 Z9 337 U1 6 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2008 VL 8 IS 11 BP 865 EP 873 DI 10.1038/nrc2502 PG 9 WC Oncology SC Oncology GA 364YV UT WOS:000260372800011 PM 18923434 ER PT J AU Stevens, W Gelman, R Glencross, DK Scott, LE Crowe, SM Spira, T AF Stevens, Wendy Gelman, Rebecca Glencross, Deborah K. Scott, Lesley E. Crowe, Suzanne M. Spira, Thomas TI Evaluating new CD4 enumeration technologies for resource-constrained countries SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID EXTERNAL QUALITY ASSESSMENT; HIV-INFECTED INDIVIDUALS; T-LYMPHOCYTE ENUMERATION; PLATFORM FLOW-CYTOMETRY; SINGLE-PLATFORM; ABSOLUTE CD4(+); CELL COUNTS; ALTERNATIVE METHODS; FACSCOUNT SYSTEM; LIMITED SETTINGS C1 [Stevens, Wendy; Glencross, Deborah K.; Scott, Lesley E.] Univ Witwatersrand, Dept Mol Med & Haematol, Johannesburg, South Africa. [Stevens, Wendy; Glencross, Deborah K.; Scott, Lesley E.] Natl Hlth Lab Serv, Johannesburg, South Africa. [Gelman, Rebecca] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelman, Rebecca] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Crowe, Suzanne M.] Monash Univ, Macfariane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3004, Australia. [Crowe, Suzanne M.] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. [Crowe, Suzanne M.] Alfred Hosp, Melbourne, Vic, Australia. [Spira, Thomas] Ctr Dis Control & Prevent, Global Programme AIDS, NCHHSTP, CCID, Atlanta, GA 30333 USA. RP Stevens, W (reprint author), Univ Witwatersrand, Dept Mol Med & Haematol, 7 York Rd Parktown, Johannesburg, South Africa. EM wendy.stevens@nhls.ac.za NR 69 TC 18 Z9 18 U1 0 U2 1 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 NOV PY 2008 VL 6 IS 11 BP S29 EP S38 DI 10.1038/nrmicro2000 PG 10 WC Microbiology SC Microbiology GA 372EE UT WOS:000260883800005 PM 22745957 ER PT J AU Ishiai, M Kitao, H Smogorzewska, A Tomida, J Kinomura, A Uchida, E Saberi, A Kinoshita, E Kinoshita-Kikuta, E Koike, T Tashiro, S Elledge, SJ Takata, M AF Ishiai, Masamichi Kitao, Hiroyuki Smogorzewska, Agata Tomida, Junya Kinomura, Aiko Uchida, Emi Saberi, Alihossein Kinoshita, Eiji Kinoshita-Kikuta, Emiko Koike, Tohru Tashiro, Satoshi Elledge, Stephen J. Takata, Minoru TI FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID DNA-DAMAGE RESPONSE; HEMATOPOIETIC STEM-CELLS; CROSS-LINK REPAIR; HOMOLOGOUS RECOMBINATION; CORE COMPLEX; PROTEIN; IDENTIFICATION; INTERACTS; ATM; MONOUBIQUITINATION AB In response to DNA damage or replication fork stress, the Fanconi anemia pathway is activated, leading to monoubiquitination of FANCD2 and FANCI and their colocalization in foci. Here we show that, in the chicken DT40 cell system, multiple alanine-substitution mutations in six conserved and clustered Ser/Thr-Gln motifs of FANCI largely abrogate monoubiquitination and focus formation of both FANCI and FANCD2, resulting in loss of DNA repair function. Conversely, FANCI carrying phosphomimic mutations on the same six residues induces constitutive monoubiquitination and focus formation of FANCI and FANCD2, and protects against cell killing and chromosome breakage by DNA interstrand cross-linking agents. We propose that the multiple phosphorylation of FANCI serves as a molecular switch in activation of the Fanconi anemia pathway. Mutational analysis of putative phosphorylation sites in human FANCI indicates that this switch is evolutionarily conserved. C1 [Ishiai, Masamichi; Kitao, Hiroyuki; Tomida, Junya; Uchida, Emi; Saberi, Alihossein; Takata, Minoru] Kyoto Univ, Ctr Radiat Biol, Dept Late Effect Studies, Lab DNA Damage Signaling,Sakyo Ku, Kyoto 6068501, Japan. [Kitao, Hiroyuki; Kinomura, Aiko; Takata, Minoru] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Human Genet, Minami Ku, Hiroshima 7348553, Japan. [Smogorzewska, Agata; Elledge, Stephen J.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Genet, Ctr Genet & Genom,Howard Hughes Med Inst, Boston, MA 02115 USA. [Smogorzewska, Agata] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kinoshita, Eiji; Kinoshita-Kikuta, Emiko; Koike, Tohru] Hiroshima Univ, Grad Sch Biomed Sci, Dept Funct Mol Sci, Minami Ku, Hiroshima 7348553, Japan. [Tashiro, Satoshi] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Cellular Biol, Minami Ku, Hiroshima 7348553, Japan. RP Takata, M (reprint author), Kyoto Univ, Ctr Radiat Biol, Dept Late Effect Studies, Lab DNA Damage Signaling,Sakyo Ku, Yoshidakonoe Cho, Kyoto 6068501, Japan. EM mtakata@house.rbc.kyoto-u.ac.jp RI Smogorzewska, Agata/B-8891-2011 FU Ministry of Education, Science, Sports, and Culture of Japan; Ministry of Health, Labour, and Welfare; US National Institute of Allergy and Infectious Diseases [1U19A1067751]; US National Institutes of Health; Novartis Foundation (Japan); Uehara Memorial Foundation; Howard Hughes Medical Institute; [T32CA09216] FX We would like to thank T. Natsume (National Institute of Advanced Industrial Science and Technology, Japan), K. Komatsu (Kyoto University), H. Kurumizaka (Waseda University), J. Lin and J. W. Harper (Harvard Medical School) for reagents; R. Sasaki (Digital Microsystems) for advice and help in microscopy; K. Namikoshi for expert technical help; and H. Shimamoto and S. Arai for secretarial assistance. This work was supported in part by Grants-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan (M. T.), by grants from Ministry of Health, Labour, and Welfare (M. T.), and by US National Institute of Allergy and Infectious Diseases grant 1U19A1067751 and US National Institutes of Health grants (S. J. E.). A. Smogorzewska is supported by T32CA09216 to the MGH Pathology Department. Financial support was also provided by The Novartis Foundation (Japan) for the Promotion of Science (M. T.) and The Uehara Memorial Foundation (M. T.). S. J. E. is funded by the Howard Hughes Medical Institute. NR 38 TC 118 Z9 122 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD NOV PY 2008 VL 15 IS 11 BP 1138 EP 1146 DI 10.1038/nsmb.1504 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 368QV UT WOS:000260638500010 PM 18931676 ER PT J AU Rodriguez, M Felsenfeld, AJ AF Rodriguez, Mariano Felsenfeld, Arnold J. TI PTH, FGF-23 and early CKD SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcium; CKD; FGF-23; phosphate; PTH ID CHRONIC KIDNEY-DISEASE; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; MINERAL METABOLISM; PHOSPHORUS; PHOSPHATE; 1,25-DIHYDROXYVITAMIN-D; ASSOCIATION; CALCIUM C1 [Rodriguez, Mariano] Hosp Univ Reina Sofia, Unidad Invest, Serv Nefrol, Cordoba 14004, Spain. [Felsenfeld, Arnold J.] Univ Calif Los Angeles, Dept Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. [Felsenfeld, Arnold J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Rodriguez, M (reprint author), Hosp Univ Reina Sofia, Unidad Invest, Serv Nefrol, Avd Menendez Pidal S-N, Cordoba 14004, Spain. EM juanm.rodriguez.sspa@juntadeandalucia.es RI Rodriguez, teresa/H-5452-2011 NR 13 TC 1 Z9 1 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD NOV PY 2008 VL 23 IS 11 DI 10.1093/ndt/gfn438 PG 3 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 361UW UT WOS:000260153600007 ER PT J AU Sas, A Jones, R Tyor, W AF Sas, A. Jones, R. Tyor, W. TI Intra-peritoneal injection of polyclonal anti-interferon alpha antibodies cross the blood brain barrier and neutralize interferon alpha SO NEUROCHEMICAL RESEARCH LA English DT Article DE antibodies; blood brain barrier; interferon alpha ID SINDBIS VIRUS; MICE; PATHOGENESIS AB The central nervous system (CNS) is known to be an immunologically privileged organ in the body largely because the blood brain barrier (BBB) prevents the flow of large molecules, proteins, and cells from crossing into the CNS from the periphery. These restrictive properties of the BBB have made it difficult to treat CNS diseases. In this study, mice were infected intracranially (i.c.) with Sindbis virus (SV) and then treated either i.c. or intraperitoneally (i.p.) with neutralizing antibodies against interferon alpha (IFN alpha). SV infected control mice received i.p. saline. Antibodies against mouse IFN alpha were detected in the brain tissue of mice that received i.p. and i.c. injections of the antibody. ELISA analysis showed that both i.c. and i.p. antibody treated mice had significantly decreased levels of IFN alpha in the brain tissue. Also, mice that received IFN alpha neutralizing antibodies showed decreased presence of protein kinase R (PKR) measured by immunohistochemical densitometry, indicating the antibody successfully inhibited IFN alpha. The data shows that antibodies are capable of crossing the BBB and inhibiting IFN alpha, indicating that it is possible to target molecules of interest in the CNS with peripheral antibody treatment. C1 [Tyor, W.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Sas, A.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Jones, R.; Tyor, W.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Tyor, W (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM william.tyor@va.gov FU MUSC Institute of Neuroscience [NIH F31, NS054592-01A2, NIH C06 RR015455] FX This study was funded by MUSC Institute of Neuroscience Grant, NIH F31 NS054592-01A2 and NIH C06 RR015455. NR 14 TC 7 Z9 8 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 2008 VL 33 IS 11 BP 2281 EP 2287 DI 10.1007/s11064-008-9715-8 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 352GG UT WOS:000259483300014 PM 18461447 ER PT J AU Lin, FH Witzel, T Zeffiro, TA Belliveau, JW AF Lin, Fa-Hsuan Witzel, Thomas Zeffiro, Thomas A. Belliveau, John W. TI Linear constraint minimum variance beamformer functional magnetic resonance inverse imaging SO NEUROIMAGE LA English DT Article DE Event-related; fMRI; In1; Visual; MRI; Neuroimaging; LCMV; Inverse solution; MEG; Magnetoencephalography; Rapid imaging ID EVENT-RELATED FMRI; SPATIALLY FILTERED MAGNETOENCEPHALOGRAPHY; SURFACE-BASED ANALYSIS; HUMAN BRAIN ACTIVITY; DISTORTION CORRECTION; HEMODYNAMIC-RESPONSE; BLOOD OXYGENATION; CEREBRAL-CORTEX; AUDITORY FMRI; STEADY-STATE AB Accurate estimation of the timing of neural activity is required to fully model the information flow among functionally specialized regions whose joint activity underlies perception, cognition and action. Attempts to detect the fine temporal structure of task-related activity Would benefit from functional imaging methods allowing higher sampling rates. Spatial filtering techniques have been used in magnetoencephalography source imaging applications. In this work, we use the linear constraint minimal variance (LCMV) beamformer localization method to reconstruct single-shot volumetric functional magnetic resonance imaging (fMRI) data using signals acquired simultaneously from all channels of a high density radio-frequency (RF) coil array. The LCMV beamformer method generalizes the existing volumetric magnetic resonance inverse imaging (In1) technique, achieving higher detection sensitivity while maintaining whole-brain spatial coverage and 100 ms temporal resolution. In this paper, we begin by introducing the LCMV reconstruction formulation and then quantitatively assess its performance using both simulated and empirical data. To demonstrate the sensitivity and inter-subject reliability of volumetric LCMV In1, we employ an event-related design to probe the spatial and temporal properties of task-related hemodynamic signal modulations in primary visual cortex. Compared to minimum-norm estimate (MINE) reconstructions, LCMV offers better localization accuracy and superior detection sensitivity. Robust results from both single subject and group analyses demonstrate the excellent sensitivity and specificity of volumetric In1 in detecting the spatial and temporal structure of task-related brain activity. (c) 2008 Published by Elsevier Inc. C1 [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. [Lin, Fa-Hsuan; Belliveau, John W.] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Witzel, Thomas] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02138 USA. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. RP Lin, FH (reprint author), Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. EM fhlin@nmr.mgh.harvard.edu RI Lin, Fa-Hsuan/G-6988-2012; Witzel, Thomas/P-1402-2014 OI Lin, Fa-Hsuan/0000-0002-9539-1731; FU NCRR NIH HHS [P41 RR014075, P41 RR014075-11, P41 RR14075]; NIBIB NIH HHS [R01 EB000790, R01 EB006847, R01 EB006847-02, R21 EB007298, T32 EB001680]; NICHD NIH HHS [R01 HD040712]; NIDA NIH HHS [R01 DA014178, R01 DA14178]; NINDS NIH HHS [R01 NS037462] NR 75 TC 18 Z9 18 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2008 VL 43 IS 2 BP 297 EP 311 DI 10.1016/j.neuroimage.2008.06.038 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 362RV UT WOS:000260215700012 PM 18672071 ER PT J AU O'Sullivan, M Jouvent, E Saernann, PG Mangin, JF Viswanathan, A Gschwendtner, A Bracoud, L Pachai, C Chabriat, H Dichgans, M AF O'Sullivan, Mike Jouvent, Eric Saernann, Philipp G. Mangin, Jean-Francois Viswanathan, Anand Gschwendtner, Andreas Bracoud, Luc Pachai, Chahin Chabriat, Hugues Dichgans, Martin TI Measurement of brain atrophy in subcortical vascular disease: A comparison of different approaches and the impact of ischaemic lesions SO NEUROIMAGE LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; PLACEBO-CONTROLLED TRIAL; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; CEREBRAL ATROPHY; MRI; CADASIL; ROBUST; SEGMENTATION; REGISTRATION AB Measurement of brain atrophy has been proposed as a Surrogate marker in MS and degenerative dementias. Although cerebral small vessel disease predominantly affects white and subcortical grey matter, recent data suggest that whole brain atrophy is also a good indicator of clinical and cognitive status in this disease. Automated methods to measure atrophy are available that are accurate and reproducible in disease-free brains. However, optimal methods in small vessel disease have not been established and the impact of ischaemic lesions on different techniques has not been explored systematically. In this study, three contrasting techniques - Statistical Parametric Mapping 5 (SPM5), SIENAX and BrainVisa - were applied to measure cross-sectional atrophy (brain parenchymal fraction or BPF) in a large (n=143) two-centre cohort of patients with CADASIL, a genetic model of small vessel disease. All three techniques showed Similar sensitivity to trends in BPF associated with age and lesion load. No single technique was particularly vulnerable to error as a result Of lesions. Provided Major errors in registration were excluded by visual inspection, manual correction of segmentations had a negligible impact with mean errors of 0.41% for SIENAX and 0.46% for BrainVisa. BPF correlated Strongly with global cognitive function and physical disability, independent of the technique used. Correlation coefficients with the Minimental State Examination score were: BrainVisa 0.58, SIENAX 0.58, SPM5 0.60 (for all, p < 0.001). These results suggest that all three methods can be applied reliably in patients with ischaemic lesions. Choice of analysis approach for this kind of clinical question will be determined by factors other than their robustness and precision, such as a desire to explore Subtle localised changes using extensions of these processing tools. Crown Copyright (c) 2008 Published by Elsevier Inc. All rights reserved. C1 [O'Sullivan, Mike; Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Neurol Klin, D-80804 Munich, Germany. [Jouvent, Eric; Viswanathan, Anand; Chabriat, Hugues] CHU Lariboisiere, Dept Neurol, Paris, France. [Saernann, Philipp G.] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Mangin, Jean-Francois] CEA, Serv Hosp Frederic Jolliot, Unite Neuroanat Fonctionelle, Orsay, France. [Viswanathan, Anand] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. [Bracoud, Luc; Pachai, Chahin] Bioimaging Technol SAS, Lyon, France. RP O'Sullivan, M (reprint author), St Georges Univ London, Ctr Clin Neurosci, London SW17 0RE, England. EM research@mikeosuilivan.org RI turton, miranda/F-4682-2011; O'Sullivan, Michael/A-1796-2010; Jouvent, Eric/B-4320-2014; Chabriat, Hugues/G-5699-2010 OI Jouvent, Eric/0000-0001-7797-2236; Chabriat, Hugues/0000-0001-8436-6074 NR 35 TC 16 Z9 16 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2008 VL 43 IS 2 BP 312 EP 320 DI 10.1016/j.neuroimage.2008.07.049 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 362RV UT WOS:000260215700013 PM 18722537 ER PT J AU Simon, JH Kleinschmidt-DeMasters, BK AF Simon, Jack H. Kleinschmidt-DeMasters, B. K. TI Variants of Multiple Sclerosis SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Devic's Neuromyelitis optica; Balo's concentric sclerosis; Marburg MS; Schilder's disease ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; MYELINOCLASTIC DIFFUSE SCLEROSIS; DEVICS-NEUROMYELITIS-OPTICA; BALOS CONCENTRIC SCLEROSIS; SCHILDERS-DISEASE; MAGNETIZATION-TRANSFER; CLINICAL-COURSE; WATER CHANNEL; MRI FEATURES; SPINAL-CORD AB The classic multiple sclerosis variants including Devic's neuromyelitis optica (NMO), Balo's concentric Sclerosis, Schilder's disease, and Marburg MS are both interesting and instructive from a disease pathophysiology perspective. Although rare, the variants are important as they often arise in the differential diagnosis for severe, acute demyelinating disease, including MS and-acute disseminated encephalomyelitis. In the case of NMO, an originally unsuspected and entirely new pathophysiology based on water channels has been described, only after the recent original description of the more specific diagnostic test for NMO based on serum immunoglobulin. C1 [Simon, Jack H.] Portland VA Med Ctr, Portland, OR 97207 USA. [Simon, Jack H.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97201 USA. [Simon, Jack H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Kleinschmidt-DeMasters, B. K.] Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. [Kleinschmidt-DeMasters, B. K.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. [Kleinschmidt-DeMasters, B. K.] Univ Colorado, Hlth Sci Ctr, Dept Neurosurg, Denver, CO 80262 USA. RP Simon, JH (reprint author), Portland VA Med Ctr, Mail Stop P2IMAG,3710 SW Vet Hosp Rd, Portland, OR 97207 USA. EM jack.simon3@va.gov NR 54 TC 6 Z9 9 U1 1 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2008 VL 18 IS 4 BP 703 EP 716 DI 10.1016/j.nic.2008.06.003 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 382ZE UT WOS:000261643100011 PM 19068410 ER PT J AU Gaman, A Kuo, B AF Gaman, Alexandru Kuo, Braden TI Neuromodulatory Processes of the Brain-Gut Axis SO NEUROMODULATION LA English DT Review DE Brain-gut axis; electrical stimulation; neuromodulation ID IRRITABLE-BOWEL-SYNDROME; SPINAL-CORD STIMULATION; SACRAL NERVE-STIMULATION; GASTRIC ELECTRICAL-STIMULATION; LOWER ESOPHAGEAL SPHINCTER; SLOW-TRANSIT CONSTIPATION; GUINEA-PIG ILEUM; VISCERAL PAIN; SMALL-INTESTINE; FECAL INCONTINENCE AB Brain-gut axis represents a complex reflex circuit that integrates the communication between cortex and the digestive system. Disturbances of the neuromodulatory processes in the brain-gut axis generate functional digestive disorders mainly centered on the pain symptoms and motility disorders. This article reviews structural and pathophysiologic aspects of the brain-gut axis and explains how the neuromodulatory interventions currently used in order to treat gastrointestinal conditions related to the brain-gut axis disturbances. The neuromodulation can be realized by pharmacologic targeting mainly receptors in the periphery or using electrical stimulation applied at different levels of the nervous system or directly in the muscular layers of the bowels resulting in modulation of the digestive system activity. The efficacy of the methods using electrostimulation is dependent on the parameters of the physical system used: amplitude, frequency, burst time of the electrical current, and also the positioning of the electrodes. While pharmacologic interventions are largely used at the moment, neuromodulatory interventions involving electrical stimulation showed clinical efficacy in research trials and have promise. C1 [Gaman, Alexandru; Kuo, Braden] Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kuo, B (reprint author), Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM bkuo@partners.org FU National Institute of Health [K23 DK069614-01] FX Founded by National Institute of Health, grant K23 DK069614-01. NR 101 TC 10 Z9 11 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1094-7159 J9 NEUROMODULATION JI Neuromodulation PD NOV PY 2008 VL 11 IS 4 BP 249 EP 259 DI 10.1111/j.1525-1403.2008.00172.x PG 11 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA 358YT UT WOS:000259954100002 PM 19844605 ER PT J AU Murphy, DL Fox, MA Timpano, KR Moya, PR Ren-Patterson, R Andrews, AM Holmes, A Lesch, KP Wendland, JR AF Murphy, Dennis L. Fox, Meredith A. Timpano, Kiara R. Moya, Pablo R. Ren-Patterson, Renee Andrews, Anne M. Holmes, Andrew Lesch, Klaus-Peter Wendland, Jens R. TI How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems SO NEUROPHARMACOLOGY LA English DT Review DE Homeostasis; Serotonin transporter; Anxiety; Obsessive-compulsive disorder; Depression; Epistasis ID OBSESSIVE-COMPULSIVE DISORDER; KNOCK-OUT MICE; POSITRON-EMISSION-TOMOGRAPHY; IRRITABLE-BOWEL-SYNDROME; PRIMARY PULMONARY-HYPERTENSION; DEFICIT HYPERACTIVITY DISORDER; 5-HT2A PROMOTER POLYMORPHISM; CATECHOL O-METHYLTRANSFERASE; ANTIDEPRESSANT-INDUCED MANIA; BIOGENIC-AMINE TRANSPORTERS AB Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species: an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene: and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species. Published by Elsevier Ltd. C1 [Murphy, Dennis L.; Fox, Meredith A.; Timpano, Kiara R.; Moya, Pablo R.; Wendland, Jens R.] NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Timpano, Kiara R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ren-Patterson, Renee] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Andrews, Anne M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Andrews, Anne M.] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Lesch, Klaus-Peter] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. [Wendland, Jens R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. EM dennismurphy@mail.nih.gov RI Andrews, Anne/B-4442-2011; Wendland, Jens/A-1809-2012; Timpano, Kiara/C-8760-2012; Lesch, Klaus-Peter/J-4906-2013; OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X; Timpano, Kiara/0000-0002-0665-8722 FU NIMH, NIH; NARSAD 2007 Young Investigator Award; NIMH Division of Intramural Research Programs Julius Axelrod Memorial Fellowship Training Award FX This research was supported by the Intramural Research Program of the NIMH, NIH. Jens R. Wendland, M.D. was also supported by a NARSAD 2007 Young Investigator Award and an NIMH Division of Intramural Research Programs Julius Axelrod Memorial Fellowship Training Award. The authors are also grateful to Theresa B. DeGuzman, Teresa Tolliver, Su-Jan Huang and Justin LaPorte for their assistance in these studies. NR 290 TC 124 Z9 128 U1 5 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2008 VL 55 IS 6 BP 932 EP 960 DI 10.1016/j.neuropharm.2008.08.034 PG 29 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 373OX UT WOS:000260982700003 PM 18824000 ER PT J AU Leritz, EC McGlinchey, RE Lundgren, K Grande, LJ Milberg, WP AF Leritz, Elizabeth C. McGlinchey, Regina E. Lundgren, Kristine Grande, Laura J. Milberg, William P. TI Using Lexical Familiarity Judgments to Assess Verbally Mediated Intelligence in Aphasia SO NEUROPSYCHOLOGY LA English DT Article DE premorbid intelligence; lexical processing; lexical-semantics; aphasia ID MENTAL-STATE-EXAMINATION; TRAUMATIC BRAIN-INJURY; COGNITIVE RESERVE; PERFORMANCE; IQ; IMPAIRMENT; OLDER; RECOGNITION; EDUCATION; DEMENTIA AB In this study. a task using forced-choice lexical familiarity judgments of irregular versus archaic words (a newly developed measure called the Lexical Orthographic Familiarity Test: LOFT) was compared to a standardized oral word-reading measure (the Wechsler Test of Adult Reading WTAR) in a group of 35 aphasic adults and a comparison group of 125 community dwelling, nonbrain damaged adults. When compared to the comparison group, aphasics had significantly lower scores on the WTAR but not the LOFT. Although both the WTAR and LOFT were significantly correlated with education in the nonbrain-damaged group, only the LOFT was correlated with education and also with the Barona full scale IQ index in the aphasic group. Lastly, WTAR performance showed a significantly greater relationship to the severity of language disorder in the aphasic group than did the LOFT. These results have both theoretical and clinical implications for the assessment of language-disordered adults, as they indicate that patients with aphasia may retain aspects of verbally mediated intelligence, and that the LOFT may provide a better estimate of premorbid functioning in aphasia than other currently available measures. C1 [Leritz, Elizabeth C.; Milberg, William P.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, GRECC, Cambridge, MA 02138 USA. [Lundgren, Kristine] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Leritz, EC (reprint author), 150 S Huntington Ave,GRECC 182 JP, Boston, MA 02130 USA. EM bleritz@heartbrain.coni RI McGlinchey, Regina/R-1971-2016 FU National Institute of Neurological Disorders and Stroke [F32NS051942]; National Institute of Deafness and Communication Disorders [5P30DC005207]; Medical Research Service VA Merit Review Awards FX This research was supported by a grant from the National Institute of Neurological Disorders and Stroke (F32NS051942), by a grant from the National Institute of Deafness and Communication Disorders (5P30DC005207), and by Medical Research Service VA Merit Review Awards to William Milberg and Regina McGlinchey. We thank Martin L. Albert, MD, PhD, for his support of this project. We would also like to thank Jacque Spitzer for her assistance with data collection, and Carol Cayer-Meade. Patricia Fitzpatrick, PhD, and Marjorie Nicholas, PhD, for conducting speech and language evaluations. Finally, we would like to thank Bruce Crosson, PhD, for his helpful comments on an earlier version of this article. and one of the anonymous reviewers whose detailed and thoughtful comments greatly improved the final version. NR 46 TC 4 Z9 4 U1 3 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD NOV PY 2008 VL 22 IS 6 BP 687 EP 696 DI 10.1037/a0013319 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 367JT UT WOS:000260549000001 PM 18999341 ER PT J AU Perlis, RH Moorjani, P Fagerness, J Purcell, S Trivedi, MH Fava, M Rush, AJ Smoller, JW AF Perlis, Roy H. Moorjani, Priya Fagerness, Jesen Purcell, Shaun Trivedi, Madhukar H. Fava, Maurizio Rush, A. John Smoller, Jordan W. TI Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: Association of TREK1 and treatment resistance in the STAR*D study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE depression; genetic; treatment-resistant; SSRI ID SEQUENCED TREATMENT ALTERNATIVES; REPORT QIDS-SR; DEPRESSIVE SYMPTOMATOLOGY; POTASSIUM CHANNEL; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; INDUCED INHIBITION; MAJOR DEPRESSION; RATING-SCALE; CITALOPRAM AB Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (KCNK2 (TREK1), SLC18A2 (VMAT2), S100A10, and HDAC5) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C(16)) score <= 5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in KCNK2 were associated with treatment response (Bonferroni-corrected, gene-based empirical p < 0.001). In follow-up analyses, KCNK2 was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (n = 225). These findings indicate that genetic variation in KCNK2 may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response. C1 [Perlis, Roy H.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Perlis, Roy H.; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Perlis, Roy H.; Moorjani, Priya; Fagerness, Jesen; Purcell, Shaun; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. [Trivedi, Madhukar H.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org OI Rush, Augustus/0000-0003-2004-2382 FU NIMH [N01 MH-90003, K23MH67060]; NARSAD; Bowman Family Foundation award; Forest Laboratories; Wyeth; Pfizer; GlaxoSmithKline; Bristol-Myers Squibb FX The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study is supported by federal funds from NIMH under contract N01 MH-90003 to the University of TexasSouthwestern Medical Center at Dallas (AJ Rush, principal investigator). Dr Perlis is supported by NIMH K23MH67060, a NARSAD Young Investigator Award, and a Bowman Family Foundation award. We thank Rutgers Cell and DNA Repository for extracting DNA and for providing samples. We appreciate the support of Forest Laboratories, Wyeth, Pfizer, GlaxoSmithKline, and Bristol-Myers Squibb for providing medications at no cost to the STAR*D study. We also thank Stephen Wisniewski, PhD, and Heather Eng for providing the clinical data. We thank the STAR*D research team, who conducted the clinical study and obtained the clinical data and the blood samples for these analyses. Finally, we thank the study participants without whom this study would not have been possible. NR 46 TC 54 Z9 59 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2008 VL 33 IS 12 BP 2810 EP 2819 DI 10.1038/npp.2008.6 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 359SB UT WOS:000260007300003 PM 18288090 ER PT J AU Sarna, L Bialous, SA Jun, HJ Wewers, ME Cooley, ME Feskanich, D AF Sarna, Linda Bialous, Stella Aguinaga Jun, Hee-Jin Wewers, Mary Ellen Cooley, Mary E. Feskanich, Diane TI Smoking Trends in the Nurses' Health Study (1976-2003) SO NURSING RESEARCH LA English DT Article DE cigarette smoking; nurse; smoking cessation; tobacco smoking ID NATIONAL DEATH INDEX; OF-THE-LITERATURE; TOBACCO DEPENDENCE; NURSING-STUDENTS; SUBSTANCE USE; CESSATION; BEHAVIOR; INTERVENTION; SPECIALTIES; WOMEN AB Background: Smoking trends among nurses are important to monitor as smoking negatively affects their health and decreases their likelihood of providing cessation interventions to patients. Objectives: The objective of the study was to describe the changes in smoking trends in the participants in the Nurses' Health Study (NHS) cohorts over 27 years. Methods: An analysis of biennial changes in smoking status and cigarette consumption within nine 5-year birth cohorts (1920-1924 to 1960-1964) and age-specific mortality rates by smoking status were examined in 237,648 female registered nurses (RNs): NHS (ages of 30-55 years in 1976, followed through 2002) and NHS II (ages of 25-42 years in 1989, followed through 2003). Results: Current smokers constituted 33.2% of NHS in 1976 and 13.5% of NHS II in 1989. Smoking rates declined in all birth cohorts; 8.4% were smoking in 2002/2003. Seventynine percent of nurses who ever smoked had quit. The mean cigarettes per day declined over time but still exceeded half a pack per day (15.1 cigarettes) at the end of follow-up. The mortality rate among current smokers was higher than that of former smokers and was approximately twice that of never smokers in all age categories; those who smoked were more likely to have comorbid conditions. Discussion: This study provides the first report of smoking trends among RNs in the NHS. The decline in smoking rate among female nurses mirrors the decline in smoking rate among women in the United States over the past 25 years. Increased mortality and morbidity rates indicate the devastating cost of smoking to the profession and can provide support for the urgent need for further research to encourage continued smoking cessation efforts for nursing professionals. C1 [Sarna, Linda] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Bialous, Stella Aguinaga] Tobacco Policy Int, San Francisco, CA USA. [Jun, Hee-Jin; Feskanich, Diane] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Jun, Hee-Jin; Feskanich, Diane] Harvard Univ, Sch Med, Boston, MA USA. [Wewers, Mary Ellen] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. RP Sarna, L (reprint author), Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. FU The Robert Wood Johnson Foundation [55769]; National Cancer Institute [CA 92696-02]; National Institutes of Health. [CA87979, CA50385] FX This project was supported by a grant from The Robert Wood Johnson Foundation (55769, Sarna) and funding front the National Cancer Institute 1 K07 (CA 92696-02, Cooley). The Nurses' Health Study is supported by Grants CA87979 and CA50385 from the National Institutes of Health. NR 49 TC 37 Z9 37 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD NOV-DEC PY 2008 VL 57 IS 6 BP 374 EP 382 DI 10.1097/NNR.0b013e31818bf38b PG 9 WC Nursing SC Nursing GA 377DB UT WOS:000261230800002 PM 19018212 ER PT J AU Albertson, AM Thompson, D Franko, DL Kleinman, RE Barton, BA Crockett, SJ AF Albertson, Ann M. Thompson, Douglas Franko, Debra L. Kleinman, Ronald E. Barton, Bruce A. Crockett, Susan J. TI Consumption of breakfast cereal is associated with positive health outcomes: evidence from the National Heart, Lung, and Blood Institute Growth and Health Study SO NUTRITION RESEARCH LA English DT Article DE Cereal; Health; Physical activity; Adolescents; Breakfast; Humans ID BODY-MASS INDEX; TO-EAT CEREALS; NUTRIENT INTAKE; CHILDHOOD OBESITY; PHYSICAL-ACTIVITY; BEVERAGE CHOICES; ADOLESCENT GIRLS; AFRICAN-AMERICAN; SCHOOL-CHILDREN; WEIGHT CHANGE AB The purpose of this study was to examine 3 possible explanations for the documented association between cereal consumption and positive health outcomes. The study design was a descriptive, longitudinal study known as the National Heart, Lung, and Blood Institute Growth Health Study. Data from annual 3-day food records were analyzed to answer study questions. The National Heart, Lung, and Blood Institute Growth Health Study recruited 2379 girls (1166 white and 1213 black), age 9 to 10 at baseline. Frequency of consumption of breakfast cereal; other types of floods eaten at breakfasts and macronutrients, micronutrients, beverages, and fruits and vegetables and physical activity were the main Outcome measures. The association of type of breakfast (cereal breakfast vs breakfast without cereal) with the outcomes of interest was estimated using regression techniques. The major findings were (1) cereal consumed at breakfast provided more fiber, iron, folic acid, and zinc and less fat, sodium, sugar, and cholesterol, compared with file nutrients in foods eaten during noncereal breakfasts. The cereal consumed provided less protein, carbohydrates, and calcium, compared to foods consumed during noncercal breakfasts; (2) eating cereal for breakfast appeared to facilitate milk consumption (leading to increased calcium intake) and to displace fats/sweets, quick breads, soda, and meat/eggs as breakfast foods. Eating cereal at breakfast was associated with increased consumption of fiber and carbohydrates and decreased consumption of fats throughout the days and (3) greater physical activity was also associated with cereal breakfast. In Conclusion, cereal consumption as part of a healthy lifestyle may play a role in maintaining adequate nutrient intake and physical activity among girls. (C) 2008 Elsevier Inc. All rights reserved. C1 [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Albertson, Ann M.; Crockett, Susan J.] Gen Mills Inc, Bell Inst Hlth & Nutr, Minneapolis, MN 55427 USA. [Thompson, Douglas; Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD 21210 USA. [Franko, Debra L.; Kleinman, Ronald E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Franko, DL (reprint author), Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. EM d.franko@neu.edu OI Barton, Bruce/0000-0001-7878-8895 FU General Mills Inc (Minneapolis, Minn); National Heart, Lung, and Blood Institute (NHLBI) [HL/DK71122]; NGHS [HC55023-26] FX This research was supported by General Mills Inc (Minneapolis, Minn) and by a grant from the National Heart, Lung, and Blood Institute (NHLBI) (HL/DK71122). The manuscript was completed while one of the authors (DF) was a distinguished research fellow at the Institute for Advanced Study and the School of Psychological Science at La Trobe University, Melbourne, Australia. The work was also supported by contracts HC55023-26 and Cooperative Agreements U01-HL-48941-44. Participating NGHS centers included Children's Medical Center, Cincinnati, Ohio (Stephen R. Daniels, principal investigator; John A. Morrison, coinvestigator); Westat Inc, Rockville, Md (George B. Schreiber, principal investigator; Ruth Striegel-Moore coinvestigator), and University of California, Berkeley, Calif (Zak I. Sabry, principal investigator; Patricia B. Crawford, coinvestigator); Maryland Medical Research Institute, Baltimore, Md (Bruce A. Barton, principal investigator) served as the data coordinating center. Program office: NHLBI (Eva Obarzanek, Phi), MPH, RD, project officer [1992-2007]; Gerald H. Payne, project officer [1985-1991]). NR 44 TC 32 Z9 33 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD NOV PY 2008 VL 28 IS 11 BP 744 EP 752 DI 10.1016/j.nutres.2008.09.002 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 375TV UT WOS:000261137100003 PM 19083483 ER PT J AU Ginde, AA Foianini, A Renner, DM Valley, M Camargo, CA AF Ginde, Adit A. Foianini, Anthony Renner, Daniel M. Valley, Morgan Camargo, Carlos A., Jr. TI The Challenge of CT and MRI Imaging of Obese Individuals Who Present to the Emergency Department: A National Survey SO OBESITY LA English DT Article AB The objective of this study was to estimate the availability of large weight capacity computed tomography (CT) and magnetic resonance imaging (MRI) equipment in US hospitals with emergency departments (EDs) and to evaluate animal facilities as alternate sources of imaging. We conducted a telephone survey of radiology technicians from a random sample of all the US hospitals with EDs (n = 262) and all 136 primary hospitals of academic EDs, 145 zoos, and 28 veterinary schools. We measured the prevalence of large weight capacity (>450 lb) CT and MRI, stratified by hospital characteristics. Response rates were 94-100% across samples. Nationally, 10% (95% confidence interval, 7-15) of hospitals with EDs had large weight capacity CT and 8% (95% confidence interval, 5-13) had large weight capacity MRI. In academic hospitals, access to large capacity equipment was better for CT (28%), but similar for MRI (10%) (P < 0.001 and 0.51, respectively). Few rural (5%) and critical-access hospitals (3%) had large capacity CT. In addition, 34% of trauma centers, 23% of stroke centers, and 21% of bariatric surgery centers of excellence had large capacity CT. Only two zoos (1%) had CT scanners; both would not image human patients. Among veterinary schools, 16 (57%) had large weight capacity CT equipment, but only 4 (14%) would consider imaging human patients. Further, 23 (82%) veterinary schools reported policies that specifically prohibited imaging humans. For patients who weigh >450 lb, access to emergent CT and MRI is limited, even at academic and bariatric surgery centers. Animal facilities are not a viable alternative for diagnostic imaging of human patients. C1 [Ginde, Adit A.; Foianini, Anthony; Renner, Daniel M.; Valley, Morgan] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Ginde, AA (reprint author), Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO USA. EM adit.ginde@uchsc.edu RI Siry, Bonnie/D-7189-2017 NR 14 TC 15 Z9 15 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD NOV PY 2008 VL 16 IS 11 BP 2549 EP 2551 DI 10.1038/oby.2008.410 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 368OO UT WOS:000260631700026 PM 18787528 ER PT J AU Garrett, LA Garner, EIO Feltmate, CM Goldstein, DP Berkowitz, RS AF Garrett, Leslie A. Garner, Elizabeth I. O. Feltmate, Colleen M. Goldstein, Donald P. Berkowitz, Ross S. TI Subsequent Pregnancy Outcomes in Patients With Molar Pregnancy and Persistent Gestational Trophoblastic Neoplasia SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Garrett, Leslie A.] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol,New England Trophoblast Dis, Div Gynecol Oncol,Sch Med,Trophoblast Tumor Regis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Garrett, LA (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol,New England Trophoblast Dis, Div Gynecol Oncol,Sch Med,Trophoblast Tumor Regis, Boston, MA 02115 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 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD NOV PY 2008 VL 63 IS 11 BP 704 EP 705 DI 10.1097/01.ogx.0000335639.50781.79 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371TP UT WOS:000260854500015 ER PT J AU Shiften, JL Monz, BU Russo, PA Segreti, A Johannes, CB AF Shiften, Jan L. Monz, Brigitta U. Russo, Patricia A. Segreti, Anthony Johannes, Catherine B. TI Sexual Problems and Distress in United States Women Prevalence and Correlates SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID QUALITY-OF-LIFE; DESIRE DISORDER; NATIONAL-SURVEY; DYSFUNCTION; HEALTH; POPULATION; MEN; RELIABILITY; ATTITUDES; VALIDITY AB OBJECTIVE: To estimate the prevalence of self-reported sexual problems (any, desire, arousal, and orgasm), the prevalence of problems accompanied by personal distress, and to describe related correlates. METHODS: The 31,581 female respondents aged 18 years and older were from 50,002 households sampled from a national research panel representative of U.S. women. Correlates of each distressing sexual problem were evaluated using multiple logistic regression techniques. RESULTS: The age-adjusted point prevalence of any sexual problem was 43.1% and 22.2% for sexually related personal distress (defined as a score of at least 15 on Female Sexual Distress Scale). Any distressing sexual problem (defined as reporting both a sexual problem and sexually related personal distress, Female Sexual Distress Scale score of at least 15) occurred in 12.0% of respondents and was more common in women aged 45-64 years (14.8%) than in younger (10.8%) or older (8.9%) women. Correlates of distressing sexual problems included poor self-assessed health, low education level, depression, anxiety, thyroid conditions, and urinary in-continence. CONCLUSION: The prevalence of distressing sexual problems peaked in middle-aged women and was considerably lower than the prevalence of sexual problems. This underlines the importance of assessing the prevalence of sexually related personal distress in accurately estimating the prevalence of sexual problems that may require clinical intervention. (Obstet Gynecol 2008;-112:970-8) C1 [Shiften, Jan L.] Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. PRC Hlth Serv Res & Management Consulting, Washington, DC USA. RTI Hlth Solut, Res Triangle Pk, NC USA. RTI Hlth Solut, Waltham, MA USA. RP Shiften, JL (reprint author), Massachusetts Gen Hosp, Vincent OB GYN Serv, 55 Fruit St,Yawkey 10-A, Boston, MA 02114 USA. EM jshifren@partners.org FU Boehringer Ingelheim International GmbH FX Funded by Boehringer Ingelheim International GmbH. NR 36 TC 371 Z9 382 U1 5 U2 40 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2008 VL 112 IS 5 BP 970 EP 978 DI 10.1097/AOG.0b013e3181898cdb PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 366TR UT WOS:000260506800002 PM 18978095 ER PT J AU Bortfeld, T Chan, TCY Trofimov, A Tsitsiklis, JN AF Bortfeld, Thomas Chan, Timothy C. Y. Trofimov, Alexei Tsitsiklis, John N. TI Robust Management of Motion Uncertainty in Intensity-Modulated Radiation Therapy SO OPERATIONS RESEARCH LA English DT Article ID RESPIRATORY MOTION; IMRT OPTIMIZATION; DOSE DISTRIBUTION; ORGAN MOTION; RADIOTHERAPY; PROBABILITY; CANCER; CT; GENERATION AB Radiation therapy is subject to uncertainties that need to be accounted for when determining a suitable treatment plan for a cancer patient. For lung and liver tumors, the presence of breathing motion during treatment is a challenge to the effective and reliable delivery of the radiation. In this paper, we build a model of motion uncertainty using probability density functions that describe breathing motion, and provide a robust formulation of the problem of optimizing intensity-modulated radiation therapy. We populate our model with real patient data and measure the robustness of the resulting solutions on a clinical lung example. Our robust framework generalizes current mathematical programming formulations that account for motion, and gives insight into the trade-off between sparing the healthy tissues and ensuring that the tumor receives sufficient dose. For comparison, we also compute solutions to a nominal (no uncertainty) and margin (worst-case) formulation. In our experiments, we found that the nominal solution typically underdosed the tumor in the unacceptable range of 6% to 11%, whereas the robust solution underdosed by only 1% to 2% in the worst case. In addition, the robust solution reduced the total dose delivered to the main organ-at-risk (the left lung) by roughly 11% on average, as compared to the margin solution. C1 [Bortfeld, Thomas; Trofimov, Alexei] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bortfeld, Thomas; Trofimov, Alexei] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chan, Timothy C. Y.] MIT, Ctr Operat Res, Cambridge, MA 02139 USA. [Tsitsiklis, John N.] MIT, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM tbortfeld@partners.org; tcychan@alum.mit.edu; atrofimov@partners.org; jnt@mit.edu FU National Science Foundation [ECS-0312921]; Natural Sciences and Engineering Research Council of Canada; United States-Israel Binational Science Foundation (BSF) [2003275]; National Cancer Institute [P01-CA21239, R01-CA103904] FX The authors thank David Craft and Benjamin Martin for their help with the implementation of this method in treatment-planning software. They also appreciate the discussions with Gregory Sharp about the patient data. This research was supported in part by the National Science Foundation under grant ECS-0312921, the Natural Sciences and Engineering Research Council of Canada, the United States-Israel Binational Science Foundation (BSF) under grant 2003275, and the National Cancer Institute under grant P01-CA21239 and grant R01-CA103904. NR 35 TC 20 Z9 20 U1 4 U2 7 PU INFORMS PI HANOVER PA 7240 PARKWAY DR, STE 310, HANOVER, MD 21076-1344 USA SN 0030-364X J9 OPER RES JI Oper. Res. PD NOV-DEC PY 2008 VL 56 IS 6 BP 1461 EP 1473 DI 10.1287/opre.1070.0484 PG 13 WC Management; Operations Research & Management Science SC Business & Economics; Operations Research & Management Science GA 410GK UT WOS:000263565300010 ER PT J AU Nguyen, J Jakobiec, FA Hanna, E Fay, A AF Nguyen, John Jakobiec, Frederick A. Hanna, Eissa Fay, Aaron TI Subepidermal Calcified Nodule of the Eyelid SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Subepidermal calcified nodule, a rare form of calcinosis cutis, is a benign lesion of the eyelid that occurs in children. We report a case of a 9-year-old boy with a nodule of the right upper eyelid simulating Molluscum contagiosum. The histopathologic examination of the excised nodule confirmed the diagnosis. C1 [Nguyen, John; Jakobiec, Frederick A.; Hanna, Eissa; Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Nguyen, J (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM john_nguyen@meei.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2008 VL 24 IS 6 BP 494 EP 495 DI 10.1097/IOP.0b013e31818be82c PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 378AT UT WOS:000261294200020 PM 19033855 ER PT J AU Khalid, AN Woodworth, BA Prince, A Quraishi, SA Antunes, MB Long, FHA Bolger, WE Chiu, AG Palmer, JN Cohen, NA AF Khalid, Ayesha N. Woodworth, Bradford A. Prince, Anthony Quraishi, Sadeq A. Antunes, Marcelo B. Long, Fenella H. A. Bolger, William E. Chiu, Alexander G. Palmer, James N. Cohen, Noam A. TI Physiologic alterations in the murine model after nasal fungal antigenic exposure SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID CILIARY-BEAT FREQUENCY; MAMMALIAN RESPIRATORY-TRACT; CHRONIC RHINOSINUSITIS; EPITHELIAL-CELLS; CULTURE AB OBJECTIVE: To determine whether a recently developed murine model of fungus-induced sinonasal inflammation demonstrated alterations in ciliary activity and expression of inflammatory cytokines. STUDY DESIGN: A prospective randomized controlled study of rhinosinusitis after fungal antigenic sensitization was performed with intraperitoneal aspergillus antigen injection followed by intranasal antigen challenge for 4 weeks. Saline solution was used in a parallel fashion for control animals. SUBJECTS AND METHODS: Six mice were used to validate the model. Additional 15 mice were used for ciliary beat frequency (CBF) analysis and cytokine expression with multiplex technology. Mean values for degree of inflammation, secretory hyperplasia. CBF. and cytokine expression were compared. RESULTS: Histologic analyses demonstrated dense chronic inflammation in aspergillus-challenged animals versus sparse inflammatory cells in controls. Significant differences in mean of aspergillus-challenged versus control animals were observed in degree of inflammation (P < 0.01), secretory hyperplasia (P < 0.01), CBF (P < 0.00002), IL-1 alpha (P < 0.0002), IL-10 (P < 0.0003), IL-4 (P < 0.02) TNF-alpha (P < 0.02). and RANTES (P < 0,01). CONCLUSION: Alteration in baseline CBF accompanied by increased expression of specific inflammatory cytokines was observed in aspergillus-challenged mice. (C) 2008 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [Khalid, Ayesha N.] Penn State Coll Med, Div Otolaryngol Head & Neck Surg, Philadelphia, PA USA. [Woodworth, Bradford A.; Prince, Anthony; Antunes, Marcelo B.; Chiu, Alexander G.; Palmer, James N.; Cohen, Noam A.] Univ Penn, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Div Rhinol, Philadelphia, PA 19104 USA. [Woodworth, Bradford A.; Palmer, James N.; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Quraishi, Sadeq A.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Long, Fenella H. A.] Univ Penn, Dept Pathol, Matthew J Ryan Sch Vet Med, Philadelphia, PA 19104 USA. [Bolger, William E.] Suburban ENT Associates, Bethesda, MD USA. RP Cohen, NA (reprint author), Hosp Univ Penn, Div Rhinol, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upewnn.edu RI Chiu, Alexander/J-1230-2014; OI Chiu, Alexander/0000-0002-7592-6575; Cohen, Noam/0000-0002-9462-3932 FU Research in Otolaryngology and Allergy Development (ROAD) Scholarship (ANK); Young Investigator Award from The Sinus and Allergy Health Partnership (NAC) FX Research was supported by a Research in Otolaryngology and Allergy Development (ROAD) Scholarship (ANK) and a Young Investigator Award from The Sinus and Allergy Health Partnership (NAC). This work was presented at the Annual Meeting of the American Rhinologic Society and the Academy of Otolaryngic Allergy (AAOA), September 2007, in Washington, DC. NR 20 TC 14 Z9 14 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2008 VL 139 IS 5 BP 695 EP 701 DI 10.1016/j.otohns.2008.07.018 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 369UR UT WOS:000260719900016 PM 18984266 ER PT J AU Undavia, M Goldstein, NE Cohen, P Sinthawanarong, K Singson, M Bhutani, D Munson, T Gomes, JA Fischer, A Mehta, D AF Undavia, Manish Goldstein, Nathan E. Cohen, Pilar Sinthawanarong, Kamoltip Singson, Magdalena Bhutani, Divaya Munson, Tracey Gomes, Joseph Anthony Fischer, Avi Mehta, Davendra TI Impact of Implantable Cardioverter-Defibrillator Recalls on Patients' Anxiety, Depression, and Quality of Life SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Scientific Session of the Heart-Rhythm-Society CY MAY 17-20, 2006 CL Boston, MA SP Heart Rhythm Soc DE ICD recalls; anxiety; depression; quality of life; case-control study ID HOSPITAL ANXIETY; PHYSICIAN COMMUNICATION; ICD RECALL; SCALE; DISEASE; SHOCKS; QUESTIONNAIRE; AMIODARONE; PREVENTION; PACEMAKER AB Background: In the past 2 years, multiple implantable cardioverter-defibrillator ( ICD) manufacturers have issued recalls on ICD models due to the potential for serious malfunction and even patient death. Previous studies examining the relationship between these recalls and patients' psychological well-being have been limited by small sample size and conflicting results. The purpose of this study is to examine the association between ICD recalls and patients' anxiety, depression, and quality of life. Methods: Patients were drawn from an outpatient electrophysiology clinic at a tertiary care hospital in New York City. Patients who had devices subject to a recall ( cases) were identified from lists provided by device manufacturer and controls ( patients with ICDs not subjected to a recall) were drawn from a convenience sample of outpatients. The survey instrument consisted of two validated questionnaires Hospital Anxiety and Depression Score ( HADS) and MacNew heart disease health-related quality of life ( QOL) instrument. In addition, a series of Likert-type scales were designed to elucidate patients' concerns related to the following domains: anger, trust, hope, concerns regarding ICD shock, fear of death ( FOD), and physicians' ability to reduce their concern about the ICD recall. Data were analyzed using simple descriptive statistics and bivariate analyses (x(2) and t-test) as appropriate. Result: Sixty-one cases and 43 control patients were enrolled. Thirty-two patients ( 52%) with devices subject to a recall opted for a generator replacement. There were no significant differences in the mean scores on the HADS scale, or the MacNew QOL scale between these two groups of patients ( cases and controls). Subgroup analysis within the group of patients whose ICDs were recalled ( cases) revealed a reduced QOL among patients with a class I recall ( reasonable probability that the product will cause serious adverse health consequences or death) as compared to those with a class II recall ( product may cause temporary or medically reversible adverse health consequences) ( P = 0.01). Both cases and control patients reported having reduced trust in the health-care system. On the whole, however, patients were satisfied with the way their physicians dealt with the recall. There was no significant change in the overall concern of ICD shocks or FOD between the two groups. Conclusion: In this study of ICD recall, we found no difference in the levels of anxiety, depression, or QOL expressed by patients with an ICD subject to a recall as compared to those without. These findings may be a reflection of good physician-patient communication, which might have reduced any anxiety associated with recalls. ( PACE 2008; 31: 1411 - 1418) C1 [Undavia, Manish; Cohen, Pilar; Sinthawanarong, Kamoltip; Singson, Magdalena; Bhutani, Divaya; Munson, Tracey; Gomes, Joseph Anthony; Fischer, Avi; Mehta, Davendra] Mt Sinai Sch Med, Dept Med, Div Cardiol, New York, NY USA. [Goldstein, Nathan E.] Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. James J Peters VA Med Ctr, Bronx, NY USA. RP Undavia, M (reprint author), Mt Sinai Med Ctr, Dept Cardiol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM manish.undavia@mssm.edu FU NIA NIH HHS [K23 AG025933-03, K23 AG025933-01A1, 1 K23 AG025933-01A1, K23 AG025933] NR 33 TC 18 Z9 18 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD NOV PY 2008 VL 31 IS 11 BP 1411 EP 1418 DI 10.1111/j.1540-8159.2008.01204.x PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 391AA UT WOS:000262203600007 PM 18950298 ER PT J AU Rosso, AL Gallagher, RM Luborsky, M Mossey, JM AF Rosso, Andrea L. Gallagher, Rollin M. Luborsky, Mark Mossey, Jana M. TI Depression and Self-Rated Health Are Proximal Predictors of Episodes of Sustained Change in Pain in Independently Living, Community Dwelling Elders SO PAIN MEDICINE LA English DT Article DE Pain; Depression; Self-Rated Health; Aged; Epidemiology; Risk Factor ID OSTEOARTHRITIS PROJECT NORSTOP; OLDER-ADULTS; UNITED-STATES; GENERAL-POPULATION; AFRICAN-AMERICAN; CARE; DISABILITY; SCALE; INTERFERENCE; PREVALENCE AB To identify, in community dwelling elders, the determinants of sustained pain improvement or worsening. A longitudinal study with two baseline and 11 monthly follow-up interviews was conducted. Pain was assessed monthly using the Parmelee adaptation of the McGill Pain Inventory. Subjects included 109 Caucasian and 132 African American, Philadelphia residing Medicare recipients (65-74 years of age). To identify sustained pain change (>= 2 months), the data for each subject were reconfigured to yield 10 overlapping 3-month data segments. Each segment was classified as improved or worsened pain. Other variables included: the Geriatric Depression Scale (GDS), self-rated health (SRH), physical functioning, and number of improved or worsened medical conditions. Pain experienced (over 3-month periods) was typically stable. Sustained improved pain was more likely than worsened pain. Odds ratios obtained through Generalized Estimation Equation analyses showed that a 1-point increase in GDS scores increased the odds of worsened pain by 1.18 (1.11-1.30). Fair/poor SRH, being female, and having medical conditions worsen increased the odds of worsened pain by 4.04 (2.12-7.70), 1.63 (1.11-2.38), and 2.12 (1.42-3.16), respectively. Observed, statistically significant associations between these variables, except gender, and improved pain were in the opposite direction. With a 1-month time lag between predictor variable assessment and follow-up pain measures, the study supports temporal associations between depressive symptoms and SRH and subsequent pain change. Clinicians providing care to community dwelling elders are advised to evaluate and attend to both the depressive symptoms and SRH of their patients. C1 [Rosso, Andrea L.; Mossey, Jana M.] Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19072 USA. [Gallagher, Rollin M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Pain Med Serv, Philadelphia, PA USA. [Luborsky, Mark] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. RP Mossey, JM (reprint author), Drexel Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 1501 Race St, Philadelphia, PA 19072 USA. EM jm55@drexel.edu OI Rosso, Andrea/0000-0001-5890-9856 FU NIA NIH HHS [R01 AG015730] NR 57 TC 8 Z9 8 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV-DEC PY 2008 VL 9 IS 8 BP 1035 EP 1049 DI 10.1111/j.1526-4637.2008.00533.x PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 375HZ UT WOS:000261106100012 PM 19067830 ER PT J AU Dobscha, SK Corson, K Leibowitz, RQ Sullivan, MD Gerrity, MS AF Dobscha, Steven K. Corson, Kathryn Leibowitz, Ruth Q. Sullivan, Mark D. Gerrity, Martha S. TI Rationale, Design, and Baseline Findings from a Randomized Trial of Collaborative Care for Chronic Musculoskeletal Pain in Primary Care SO PAIN MEDICINE LA English DT Review DE Disease Management; Pain; Chronic Illness; Depression; Narcotics ID MORRIS DISABILITY QUESTIONNAIRE; PHYSICIAN JOB-SATISFACTION; CHRONIC NONMALIGNANT PAIN; CHRONIC NONCANCER PAIN; ABUSE SCREENING-TEST; SPINAL-CORD-INJURY; CHRONIC BACK-PAIN; SELF-REPORT; PATIENT SATISFACTION; MANAGEMENT PROGRAMS AB This article describes the rationale, design, and baseline findings from an ongoing study of collaborative care for chronic musculoskeletal pain and comorbid depression. Cluster randomized clinical trial. Forty-two clinicians and 401 patients from five Veterans Affairs primary care clinics. The intervention was based on the chronic care model, and included patient and provider activation and education, patient assessment, outcomes monitoring, and feedback to providers over 12 months. The intervention team consisted of a full-time psychologist care manager and a part-time physician internist. Approaches included goal setting emphasizing function, patient activation and educating about fear avoidance, and care management. Main outcomes are Roland-Morris Disability Questionnaire (RMDQ) score, depression severity (Patient Health Questionnaire-9), and pain severity (Chronic Pain Grade Severity subscale) at 6 and 12 months. Fifteen percent of primary care patients mailed a study advertisement letter requested screening for the study. The mean age of enrolled patients was 62. Back and neck or joint pain diagnoses were present in 67% and 65% of patients, respectively. Mean pain duration was 15 years, and mean RMDQ score (range 0-24) was 14.7 (standard deviation = 4.4). Sixty-five percent of patients were receiving disability. Eighteen percent of patients met criteria for major depression, 17% for posttraumatic stress disorder, and 9% for alcohol misuse. Thirty-nine percent of patients felt strongly that experiencing pain was a sign of damage, and 60% reported strong avoidance of painful activities. These baseline data support the rationale to develop a multifaceted approach to treat chronic pain in primary care that includes detection and treatment of psychiatric comorbidity. C1 [Gerrity, Martha S.] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97207 USA. [Dobscha, Steven K.; Corson, Kathryn; Leibowitz, Ruth Q.; Gerrity, Martha S.] Columbia Ctr Study Chron Comorbid Phys & Mental D, Portland, OR 97207 USA. [Dobscha, Steven K.; Corson, Kathryn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Sullivan, Mark D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Div Hosp & Specialty Med, POB 1034, R&D 66, Portland, OR 97207 USA. EM steven.dobscha@va.gov RI Duncan, Kirsty/H-1911-2011 FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service Projects [PMI 03-195, RCD04129] FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Projects PMI 03-195 and RCD04129. 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 102 TC 16 Z9 16 U1 5 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV-DEC PY 2008 VL 9 IS 8 BP 1050 EP 1064 DI 10.1111/j.1526-4637.2008.00457.x PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 375HZ UT WOS:000261106100013 PM 18565008 ER PT J AU Manchikanti, L Hirsch, JA Smith, HS AF Manchikanti, Laxmaiah Hirsch, Joshua A. Smith, Howard S. TI Evidence-Based Medicine, Systematic Reviews, and Guidelines in Interventional Pain Management: Part 2: Randomized Controlled Trials SO PAIN PHYSICIAN LA English DT Review DE Randomized controlled trial (RCT); placebo-controlled trial; pragmatic controlled trial; randomization; allocation concealment; sample size; blinding; consolidated standards of reporting trials (CONSORT) statement; minimal clinically important change (MCIC); minimal clinical important difference (MCID) ID LOW-BACK-PAIN; NECK DISABILITY INDEX; FACET JOINT PAIN; QUALITY-OF-LIFE; CLINICALLY IMPORTANT DIFFERENCE; UNDERSTANDING-CONTROLLED-TRIALS; SPINAL-CORD STIMULATION; HEALTH-STATUS MEASURES; LUMBAR RADICULAR PAIN; PERCUTANEOUS RADIOFREQUENCY NEUROTOMY AB Evidence-based medicine (EBM) is a shift in medical paradigms and about solving clinical problems, acknowledging that intuition, unsystematic clinical experience, and pathophysiologic rationale are insufficient grounds for clinical decision-making. The importance of randomized trials has been created by the concept of the hierarchy of evidence in guiding therapy. Even though the concept of hierarchy of evidence is not absolute, in modern medicine, most researchers synthesizing the evidence may or may not follow the principles of EBM, which requires that a formal set of rules must complement medical training and common sense for clinicians to interpret the results of clinical research. N of 1 randomized controlled trials (RCTs) has been positioned as the top of the hierarchy followed by systematic reviews of randomized trials, single randomized trial, systematic review of observational studies, single observational study, physiologic studies, and unsystematic clinical observations. However, some have criticized that the hierarchy of evidence has done nothing more than glorify the results of imperfect experimental designs on unrepresentative populations in controlled research environments above all other sources of evidence that may be equally valid or far more applicable in given clinical circumstances. Design, implementation, and reporting of randomized trials is crucial. The biased interpretation of results from randomized trials, either in favor of or opposed to a treatment, and lack of proper understanding of randomized trials, leads to a poor appraisal of the quality. Multiple types of controlled trials include placebo-controlled and pragmatic trials. Placebo-controlled RCTs have multiple shortcomings such as cost and length, which limit the availability for studying certain outcomes, and may suffer from problems of faulty implementation or poor generalizability, despite the study design which ultimately may not be the prime consideration when weighing evidence for treatment alternatives. However, in practical clinical trials, interventions compared in the trial are clinically relevant alternatives, participants reflect the underlying affected population with the disease, participants come from a heterogeneous group of practice settings and geographic locations, and endpoints of the trial reflect a broad range of meaningful clinical outcomes. C1 [Manchikanti, Laxmaiah] Pain Management Ctr, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Howard S.] Albany Med Coll, Dept Anesthesiol, Albany, NY 12208 USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 525 TC 96 Z9 96 U1 3 U2 12 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD NOV-DEC PY 2008 VL 11 IS 6 BP 717 EP 773 PG 57 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 383GR UT WOS:000261662600002 PM 19057624 ER PT J AU Guimaraes, AR Rakhlin, E Weissleder, R Thayer, SP AF Guimaraes, Alexander R. Rakhlin, Elena Weissleder, Ralph Thayer, Sarah P. TI Magnetic Resonance Imaging Monitors Physiological Changes With Antihedgehog Therapy in Pancreatic Adenocarcinoma Xenograft Model SO PANCREAS LA English DT Article DE angiogenesis; magnetic resonance imaging; nanoparticle; pancreatic cancer; sonic hedgehog ID HEDGEHOG SIGNALING PATHWAY; TUMOR ANGIOGENESIS; GENE-EXPRESSION; CELL-LINES; CANCER; TUMORIGENESIS; BIOLOGY; IDENTIFICATION; METASTASIS; RESECTION AB Objectives: The sonic hedgehog (Shh) pathway has an established role in pancreatic cancer (pancreatic adenocarcinoma [PDAC]). We tested whether magnetic resonance imaging measures of vascular volume fraction (VVF) using magnetic iron oxide nanoparticles are sensitive to the antiangiogenic effect of targeted Shh therapies in a PDAC xenograft model. Methods: Pancreatic adenocarcinoma xenograft lines were subcutaneously implanted into nude mice (n = 19 samples within 4 groups). Therapies were targeted to 3 loci of the Shh signaling pathway (anti-Shh antibody, cyclopamine, or forskolin). Magnetic resonance imaging (4.7-T Bruker Pharmascan) was performed (after 1 week of intraperitoneal therapy) before and after intravenous injection of MION-47. Vascular volume fraction was quantifiped as Delta R2 (from multicontrast T2 sequences) and normalized to an assumed VVF in muscle of 3%. Linear regression compared VVF to histological indices including microvessel density (MVD), viable gland density (VGD), and proliferative index (PI). Results: In response to anti-Hh treatment, tumors showed a decrease in VGD, PI, MVD, and VVF compared with controls (P < 0.001). Vascular volume fraction was compared with histological indicators of response: PI (R(2) = 0.88; P < 0.05), VGD (R(2) = 0.87; P < 0.05), and MVD (R(2) = 0.85; P < 0.05). Conclusions: Magnetic resonance imaging VVF using magnetic iron oxide nanoparticles may serve as a noninvasive measure of biological response to Shh PDAC therapy with easy translation to the clinic. C1 [Guimaraes, Alexander R.; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA USA. [Guimaraes, Alexander R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Rakhlin, Elena; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Guimaraes, AR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Div Abdominal Imaging, White 270,55 Fruit St, Boston, MA 02114 USA. EM aguimaraesl@partners.org FU Dr Thayer's Lustgarten Foundation; K08-Mentored Clinical Scientist Development Award FX This study was supported by Dr Thayer's Lustgarten Foundation and K08-Mentored Clinical Scientist Development Award ( S. P. T.). NR 30 TC 14 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 440 EP 444 DI 10.1097/MPA.0b013e31817c5113 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400016 PM 18953259 ER PT J AU Androutsopoulos, V Dominguez, I Ferrone, C Castillo, CFD Warshaw, AL Thayer, SP AF Androutsopoulos, V. Dominguez, I. Ferrone, C. Castillo, C. Fernandez-del Warshaw, A. L. Thayer, S. P. TI DOES GEMZAR IMPROVE SURVIVAL IN RESECTED PANCREATIC CANCER PATIENTS? SO PANCREAS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, 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 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 459 EP 459 DI 10.1097/01.MPA.0000335426.58851.1a PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400022 ER PT J AU Correa-Gallego, C Ferrone, C Sahani, D Forcione, D Brugge, W Thayer, SP Warshaw, AL Fernandez-del Castillo, C AF Correa-Gallego, C. Ferrone, C. Sahani, D. Forcione, D. Brugge, W. Thayer, S. P. Warshaw, A. L. Fernandez-del Castillo, C. TI INCIDENTALLY DISCOVERED PANCREATIC CYSTS: WHAT EVALUATION IS USEFUL? SO PANCREAS LA English DT Meeting Abstract C1 [Correa-Gallego, C.; Ferrone, C.; Thayer, S. P.; Warshaw, A. L.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sahani, D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Forcione, D.; Brugge, W.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 466 EP 466 DI 10.1097/01.MPA.0000335436.25099.99 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400049 ER PT J AU Konstantinidis, I Deshpande, V Catalano, OA Forcione, DG Sahani, D Castillo, CFD Thayer, SP Warshaw, AL Ferrone, CR AF Konstantinidis, I. Deshpande, V. Catalano, O. A. Forcione, D. G. Sahani, D. Castillo, C. Fernandez-del Thayer, S. P. Warshaw, A. L. Ferrone, C. R. TI LYMPHOEPITHELIAL CYSTS OF THE PANCREAS: REPORT OF A SINGLE INSTITUTION EXPERIENCE OF 8 CASES SO PANCREAS LA English DT Meeting Abstract C1 [Konstantinidis, I.; Castillo, C. Fernandez-del; Thayer, S. P.; Warshaw, A. L.; Ferrone, C. R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Deshpande, V.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Catalano, O. A.; Sahani, D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Forcione, D. G.] Massachusetts Gen Hosp, Dept GI, Boston, MA 02114 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 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 478 EP 478 DI 10.1097/01.MPA.0000335489.63636.65 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400097 ER PT J AU Nehra, D Mino-Kenudson, M Thayer, SP Ferrone, CR Finkelstein, D Silver, M Warshaw, AL del-Castillo, CF AF Nehra, D. Mino-Kenudson, M. Thayer, S. P. Ferrone, C. R. Finkelstein, D. Silver, M. Warshaw, A. L. del-Castillo, C. Fernandez TI INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS: A GENETIC DISEASE? SO PANCREAS LA English DT Meeting Abstract C1 [Nehra, D.; Mino-Kenudson, M.; Thayer, S. P.; Ferrone, C. R.; Finkelstein, D.; Silver, M.; Warshaw, A. L.; del-Castillo, C. Fernandez] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 486 EP 487 DI 10.1097/01.MPA.0000335347.96697.4c PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400135 ER PT J AU Rakonczay, Z Hegyi, P Biczo, G Dosa, S Ivanyi, B Hracsko, Z Varga, IS Gukovsky, I Gukovskaya, AS Pandol, SJ Wittmann, T Takacs, T AF Rakonczay, Z., Jr. Hegyi, P. Biczo, G. Dosa, S. Ivanyi, B. Hracsko, Z. Varga, I. S. Gukovsky, I. Gukovskaya, A. S. Pandol, S. J. Wittmann, T. Takacs, T. TI L-ORNITHINE INDUCES ACUTE NECROTIZING PANCREATITIS IN RATS SO PANCREAS LA English DT Meeting Abstract C1 [Rakonczay, Z., Jr.; Hegyi, P.; Biczo, G.; Wittmann, T.; Takacs, T.] Univ Szeged, Dept Med 1, Szeged, Hungary. [Dosa, S.; Ivanyi, B.] Univ Szeged, Dept Pathol, Szeged, Hungary. [Hracsko, Z.; Varga, I. S.] Univ Szeged, Dept Biochem & Mol Biol, Szeged, Hungary. [Gukovsky, I.; Gukovskaya, A. S.; Pandol, S. J.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 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 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 491 EP 491 DI 10.1097/01.MPA.0000335367.24513.ee PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400153 ER PT J AU Thrower, E Yuan, J Kelly, M Jones, C Pandol, S Guha, S AF Thrower, E. Yuan, J. Kelly, M. Jones, C. Pandol, S. Guha, S. TI PROTEIN KINASE D: A NOVEL REGULATOR OF ZYMOGEN ACTIVATION AND AMYLASE SECRETION IN ACUTE PANCREATITIS SO PANCREAS LA English DT Meeting Abstract C1 [Thrower, E.; Kelly, M.; Jones, C.] Vet Adm Connecticut Healthcare, Sect Digest Dis, West Haven, CT USA. [Thrower, E.; Kelly, M.; Jones, C.] Yale Univ, Sch Med, New Haven, CT USA. [Yuan, J.; Pandol, S.] VA Greater LA Hlth Care Syst, Los Angeles, CA USA. [Yuan, J.; Pandol, S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Guha, S.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol, Houston, TX 77030 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 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 498 EP 498 DI 10.1097/01.MPA.0000335400.62423.be PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400183 ER PT J AU Whitcomb, DC Muddana, V Langmead, CJ Lamb, J Papachristou, GI AF Whitcomb, D. C. Muddana, V. Langmead, C. J. Lamb, J. Papachristou, G. I. TI ANGIOPOIETIN-2, A REGULATOR OF VASCULAR PERMEABILITY IN INFLAMMATION IS ELEVATED IN SEVERE ACUTE PANCREATITIS AND IS ASSOCIATED WITH SYSTEMIC ORGAN FAILURE SO PANCREAS LA English DT Meeting Abstract C1 [Whitcomb, D. C.; Muddana, V.; Lamb, J.; Papachristou, G. I.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Whitcomb, D. C.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Whitcomb, D. C.] Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA USA. [Langmead, C. J.] Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. [Papachristou, G. I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol, Pittsburgh, PA 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 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2008 VL 37 IS 4 BP 500 EP 501 DI 10.1097/01.MPA.0000335411.31036.03 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365RL UT WOS:000260425400193 ER PT J AU Haidet, P O'Malley, KJ Sharf, BF Gladney, AP Greisinger, AJ Street, RL AF Haidet, Paul O'Malley, Kimberly J. Sharf, Barbara F. Gladney, Alicia P. Greisinger, Anthony J. Street, Richard L., Jr. TI Characterizing explanatory models of illness in healthcare: Development and validation of the CONNECT instrument SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Physician-patient relations; Cultural diversity; Patient-centered care; Anthropology; Cultural; Patient participation; Psychometrics; Primary health care ID COMMUNICATION; PATIENT; MANAGEMENT; ADHERENCE; COMMUNITY; BELIEFS; LESSONS; DOCTOR; SCALES AB Objective: A growing body of qualitative and quantitative research suggests that individual patients and physicians often have differing perspectives, or 'explanatory models,' regarding the patient's health condition of illness. Discordance between explanatory models may lead to difficulties in communication and poor disease outcomes. However, due to a lack of tools to systematically measure concordance in patient and physician explanatory models, a large-scale study of explanatory models of illness has not been previously possible. The objective of this project was to develop and pilot-test a survey-based tool (the CONNECT Instrument) that measures salient aspects of explanatory models of illness. Methods: We conducted a multi-method survey development project that included qualitative and quantitative item development, refinement, pilot testing, and psychometric evaluation. We evaluated the instrument in two unique, consecutive cohorts of primary care patients in a variety of private and public settings in Houston, TX. We also used the instrument to examine concordance between patient and physician explanatory models in the second cohort. Results: The final version of the CONNECT Instrument contains nineteen items that focus on six dimensions of explanatory models. Cronbach alphas ranged from 0.65 to 0.89 for the six CONNECT dimensions. The instrument demonstrated evidence of criterion-related validity when individual CONNECT dimension scores were compared with scores from previously published instruments, and demonstrated expected differences between patients 'and physicians' explanatory models of illness. Conclusion: The CONNECT instrument is a tool with good psychometric properties that enables researchers to measure important aspects of patients 'and physicians' explanatory models of illness. Our continuing work will focus oil gathering additional validity evidence and evaluating associations between explanatory model concordance and health outcomes. Practice implications: The CONNECT instrument can be used to improve quality in clinical practice and medical education by measuring an important intermediate outcome in the chain of factors leading to patient trust, satisfaction, and adherence. Published by Elsevier Ireland Ltd. C1 [Haidet, Paul] DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Haidet, Paul] Baylor Coll Med, Houston, TX 77030 USA. [O'Malley, Kimberly J.] Pearson Educ Measurement, Austin, TX USA. [Sharf, Barbara F.; Street, Richard L., Jr.] Texas A&M Univ, Dept Speech, College Stn, TX USA. [Gladney, Alicia P.] Harris Cty Dept Educ, Houston, TX USA. [Greisinger, Anthony J.] Kelsey Res Fdn, Houston, TX USA. [Greisinger, Anthony J.] Kelsey Seybold Clin, Houston, TX USA. RP Haidet, P (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM phaidet@bcm.edu FU AHRQ HHS [P01 HS10876] NR 32 TC 17 Z9 17 U1 0 U2 11 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 NOV PY 2008 VL 73 IS 2 BP 232 EP 239 DI 10.1016/j.pec.2008.07.007 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 374DS UT WOS:000261023500012 PM 18760889 ER PT J AU Iosifescu, A Halm, EA McGinn, T Siu, AL Federman, AD AF Iosifescu, Alice Halm, Ethan A. McGinn, Thomas Siu, Albert L. Federman, Alex D. TI Beliefs about generic drugs among elderly adults in hospital-based primary care practices SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Generic drugs; Beliefs; Elderly; Low-income; Access to care ID HEALTH LITERACY; MEDICARE BENEFICIARIES; OLDER-ADULTS; PHYSICIAN COMMUNICATION; POTENTIAL SAVINGS; PATIENTS REQUESTS; MEDICATIONS; SUBSTITUTION; ASSOCIATION; COVERAGE AB Objective: This Study aimed to characterize seniors' belief's about generic drugs, and examine potential correlates of these beliefs, including socioeconomic and health Status variables, health literacy, and physician communication skills. Methods: Older adults (>= 65 years) were interviewed in two primary care practices of an inner-city, tertiary care hospital (n = 311). Beliefs about generics were measured using a scale that compared generic and brand name drugs across four domains. Beliefs were modeled with multivariable linear regression. Results: Negative beliefs about generics were associated with non-white race (p < 0.0001), lower education (p = 0.008) and income (p = 0.001), and having Medicaid coverage (p = 0.001). Individuals with low health literacy and who reported that their physicians had poor communication skills were more likely to hold negative views (p < 0.0001 and p = 0.003, respectively). In multivariable analysis, black race (beta = -2.30. p = 0.006) and inadequate health literacy (beta = -2.17, p = 0.0004) remained strongly associated with negative views about generic drugs. Poor physician communication skills also predicted negative beliefs about generics but the association was not significant for all levels of communication skill. Conclusion: Many low-income seniors mistrust generic medications, especially African-Americans and seniors with low health literacy. Practice implications: Educational efforts to promote generic medications should account for patients' health literacy and Cultural backgrounds. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Halm, Ethan A.; McGinn, Thomas; Federman, Alex D.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Siu, Albert L.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Siu, Albert L.] Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, 1 Gustave L Levy Pl Box 1087, New York, NY 10029 USA. EM alex.federman@mssm.edu RI Mendoza, Elvia/A-9361-2012 FU Robert Wood Johnson Generalist Physician Faculty Scholars Program Award; National Institute on Aging; American Federation for Aging Research FX Funding: This project was supported by a Robert Wood Johnson Generalist Physician Faculty Scholars Program Award (Dr. Federman). Dr. Federman also receives support from the Paul B. Beeson Career Development Award Program in Aging from the National Institute on Aging and the American Federation for Aging Research. Ms. losifescu's work oil this project was supported by a Medical Student Training in Aging Research (MSTAR) Program award from the American Federation for Aging Research. NR 38 TC 33 Z9 35 U1 0 U2 3 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 NOV PY 2008 VL 73 IS 2 BP 377 EP 383 DI 10.1016/j.pec.2008.07.012 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 374DS UT WOS:000261023500033 PM 18706784 ER PT J AU DuBois, SG London, WB Zhang, Y Matthay, KK Monclair, T Ambros, PF Cohn, SL Pearson, A Diller, L AF DuBois, Steven G. London, Wendy B. Zhang, Yang Matthay, Katherine K. Monclair, Tom Ambros, Peter F. Cohn, Susan L. Pearson, Andrew Diller, Lisa TI Lung metastases in neuroblastoma at initial diagnosis: A report from the International Neuroblastoma Risk Group (INRG) project SO PEDIATRIC BLOOD & CANCER LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Society-of-Pediatric-Hematology-Oncology CY MAY 03-06, 2007 CL Toronto, CANADA SP Amer Soc Pediat Hematol Oncol DE lung metastases; MYCN; neuroblastoma; pulmonary ID PEDIATRIC-ONCOLOGY-GROUP; NEURO-BLASTOMA; TUMOR THROMBUS; STAGE-IV; PULMONARY METASTASES; AGE; PROGNOSIS; SURVIVAL AB Background. Neuroblastoma is the most common extracranial pediatric solid cancer. Lung metastasis is rarely detected in children with newly diagnosed neuroblastoma. We aimed to describe the incidence, clinical characteristics, and outcome of patients with long metastatis at initial diagnosis using a large international database. Procedure. The subset of patients from the International Neuroblastoma Risk Group database with INSS stage 4 neuroblastoma and known data regarding lung metastasis at diagnosis was selected for analysis. Clinical and biological characteristics were compared between patients with and without lung metastasis. Survival for patients with and without lung metastasis was estimated by Kaplan-Meier methods. Cox proportional hazards methods were used to determine the independent prognostic, value of lung metastasis at diagnosis. Results. Of the 2,808 patients with INSS stage 4 neuroblastoma diagnosed between 1990 and 2002, 100 patients (3.6%) were reported to have lung metastasis at diagnosis. Lung metastasis was more common among patients with MYCN amplified tumors, adrenal primary tumors, or elevated lactate dehydrogenase (LDH) levels (P<0.02 in each case). Five-year overall survival standard error for patients with lung metastasis was 34.5% +/- 6.8% compared to 44.7% +/- 1.3%. for patients Without lung metastasis P = 0.0002). However, in multivariable analysis, the presence of lung metastasis was not independently predictive of outcome. Conclusions. Lung metastasis at initial diagnosis of neuroblasloma is associated with MYCN amplification and elevated LDH levels. Although lung metastasis at diagnosis was riot independently predictive of outcome in this analysis, it remains a useful prognostic marker of unfavorable outcome. C1 [DuBois, Steven G.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [London, Wendy B.; Zhang, Yang] Univ Florida, INRG Database & Childrens Oncol Grp, Stat & Data Ctr, Gainesville, FL USA. [Monclair, Tom] Univ Oslo, Rikshosp, Natl Hosp, Dept Surg, N-0027 Oslo, Norway. [Ambros, Peter F.] St Anna Childrens Hosp, Childrens Canc Res Inst, Vienna, Austria. [Cohn, Susan L.] Univ Chicago, Inst Mol Pediat Sci, Chicago, IL 60637 USA. [Pearson, Andrew] Inst Canc Res, London SW3 6JB, England. [Pearson, Andrew] Royal Marsden Hosp, London SW3 6JJ, England. [Diller, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Diller, Lisa] Childrens Hosp, Boston, MA 02115 USA. RP DuBois, SG (reprint author), Univ Calif San Francisco, Sch Med, Dept Pediat, 505 Parnassus Ave,Box 0106, San Francisco, CA 94143 USA. EM duboiss@peds.ucsf.edu OI Ambros, Peter F./0000-0002-5507-7211; Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [U10 CA098543, U10 CA098543-07] NR 23 TC 21 Z9 25 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2008 VL 51 IS 5 BP 589 EP 592 DI 10.1002/pbc.21684 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 351ZS UT WOS:000259465400006 PM 18649370 ER PT J AU Chowdhury, F Khan, AI Harris, JB LaRocque, RC Chowdhury, MI Ryan, ET Faruque, ASG Calderwood, SB Qadri, F AF Chowdhury, Fahima Khan, Ashraful I. Harris, Jason B. LaRocque, Regina C. Chowdhury, Mohiul Islam Ryan, Edward T. Faruque, A. S. G. Calderwood, Stephen B. Qadri, Firdausi TI A Comparison of Clinical and Immunologic Features in Children and Older Patients Hospitalized With Severe Cholera in Bangladesh SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE cholera; Vibrio cholerae O1/O139; children; older patients; immunological responses ID SUBUNIT-WHOLE-CELL; VIBRIO-CHOLERAE; IMMUNE-RESPONSES; ZINC SUPPLEMENTATION; ANTIBODY-RESPONSE; ENDEMIC CHOLERA; SYNONYM BENGAL; NORTH JAKARTA; O139 BENGAL; FIELD-TRIAL AB Background: Infection with Vibrio cholerae induces protection from Subsequent severe disease, suggesting that an effective vaccine could be an important preventive strategy. Available vaccines provide less protection against cholera than natural infection, particularly in children. Methods: We examined a cohort of 121 children (2 years-12 years of age) and 276 older patients (> 12 years of age) hospitalized with cholera in Dhaka, Bangladesh over a 4-year period, to compare clinical features in older patients and children and immune responses to key antigens. Results: Older patients had more severe disease. Children with cholera were more commonly retinol deficient, while zinc deficiency was equally prevalent in both groups. Children developed higher vibriocidal and serum immune responses to the B subunit of cholera toxin (CTB). In contrast, older patients Mounted higher immune responses to 2 other key V. cholerae antigens, the lipopolysaccharide (LPS) and toxin coregulated pilus antigens (TcpA). We compared immune responses following infection with those occurring after receipt of a live, oral vaccine in both children and older patients in Bangladesh, during a similar time period. The response rates for vibriocidal and LPS antibodies were higher after infection than after vaccination. Both vaccinated older patients and children responded poorly to CTB and TcpA. Conclusions: Although children developed vigorous vibriocidal and CTB-specific responses following infection, they had lessened responses to LIPS and TcpA compared with older patients, as well as lessened responses to vaccination. More studies need to be carried Out to determine factors, including micronutrient interventions that can improve responses in children to both natural infection and vaccination. C1 [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Dhaka 1000, Bangladesh. [Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Div Sci Lab, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU FIC NIH HHS [K01 TW007409-04, D43 TW005572, D43 TW005572-05, K01 TW007144, K01 TW007144-05, K01 TW007409, K01 TW07144, K01 TW07409]; NIAID NIH HHS [R03 AI063079, R01 AI040725, R01 AI040725-09, R01 AI40725, T32 AI007061, R03 AI063079-03, U01 AI058935, U01 AI058935-09]; PHS HHS [U01 A0I58935] NR 37 TC 20 Z9 20 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2008 VL 27 IS 11 BP 986 EP 992 DI 10.1097/INF.0b013e3181783adf PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 368UO UT WOS:000260648400007 PM 18833030 ER PT J AU Lipton, J Joffe, S Ullrich, NJ AF Lipton, Jonathan Joffe, Steven Ullrich, Nicole J. TI CNS Relapse of Acute Myelogenous Leukemia Masquerading as Pseudotumor Cerebri SO PEDIATRIC NEUROLOGY LA English DT Article ID IDIOPATHIC INTRACRANIAL HYPERTENSION; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; MENINGEAL LEUKEMIA; CHILDREN AB An 18-year-old man in remission from acute myelogenous leukemia 3 years after a bone marrow transplant presented with signs of pseudotumor cerebri, including headache, visual changes, and papilledema. He manifested elevated opening pressure on lumbar puncture and positive cytology, with a concurrent normal bone marrow aspirate and biopsy. He was diagnosed with an isolated central nervous system relapse of acute myeloid leukemia. Although the precise etiology remains elusive, this case demonstrates that pseudotumor cerebri must remain within the differential diagnosis after other complications are excluded, particularly in persons with underlying hematologic malignancies. (C) 2008 Published by Elsevier Inc. C1 [Lipton, Jonathan; Ullrich, Nicole J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Joffe, Steven; Ullrich, Nicole J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ullrich, NJ (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM nicole.ullrich@childrens.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 13 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD NOV PY 2008 VL 39 IS 5 BP 355 EP 357 DI 10.1016/j.pediatrneurol.2008.07.025 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 393DY UT WOS:000262352300009 PM 18940560 ER PT J AU Chang, HL Kish, JB Smith, BL Goldstein, AM AF Chang, Henry L. Kish, Joshua B. Smith, Barbara L. Goldstein, Allan M. TI A 16-year-old male with gynecomastia and ductal carcinoma in situ SO PEDIATRIC SURGERY INTERNATIONAL LA English DT Article DE Pediatric breast disease; Male breast cancer; Male ductal carcinoma in situ; Gynecomastia ID MALE BREAST; CHILDREN; PATIENT; CANCER; BRCA2; BOY AB While gynecomastia is common in adolescents, male breast cancer in the pediatric population is exceedingly rare. Occasional reports describe malignant and pre-malignant lesions in mastectomy specimens for gynecomastia in young adults. We present a 16-year-old male with unilateral gynecomastia discovered to have ductal carcinoma in situ (DCIS), treated by mastectomy with 4 year follow-up. C1 [Chang, Henry L.; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02115 USA. [Kish, Joshua B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA USA. [Smith, Barbara L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Oncol, Boston, MA USA. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Warren 1153, Boston, MA 02115 USA. EM agoldstein@partners.org NR 18 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-0358 J9 PEDIATR SURG INT JI Pediatr. Surg. Int. PD NOV PY 2008 VL 24 IS 11 BP 1251 EP 1253 DI 10.1007/s00383-008-2246-1 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 362FZ UT WOS:000260184900014 PM 18766353 ER PT J AU Greene, R AF Greene, Ross TI Kids Do Well If They Can SO PHI DELTA KAPPAN LA English DT Article C1 [Greene, Ross] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Greene, Ross] Massachusetts Gen Hosp, Dept Psychiat, Collaborat Problem Solving Inst, Boston, MA 02114 USA. RP Greene, R (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU PHI DELTA KAPPA PI BLOOMINGTON PA 8TH AND UNION P O BOX 789, BLOOMINGTON, IN 47402 USA SN 0031-7217 J9 PHI DELTA KAPPAN JI Phi Delta Kappan PD NOV PY 2008 VL 90 IS 3 BP 160 EP 167 PG 8 WC Education & Educational Research SC Education & Educational Research GA 417CA UT WOS:000264051400004 ER PT J AU Humbert, IA Robbins, J AF Humbert, Ianessa A. Robbins, JoAnne TI Dysphagia in the Elderly SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Review ID AGE-RELATED-CHANGES; MUSCLE PROTEIN-SYNTHESIS; TRANSCRANIAL MAGNETIC STIMULATION; HUMAN THYROARYTENOID MUSCLE; WHOLE VASTUS LATERALIS; DIFFERENT FIBER TYPES; EVENT-RELATED FMRI; OLDER-ADULTS; MOTOR UNITS; CORTICAL REPRESENTATION AB The capacity to swallow or eat is a basic human need and can be a great pleasure. Older adults look forward to sharing mealtimes and participating in social interactions. The loss of capacity to swallow and dine can have far-reaching implications. With age, the ability to swallow undergoes changes that increase the risk for disordered swallowing, with devastating health implications for older adults. With the growth in the aging population, dysphagia is becoming a national health care burden and concern. Upward of 40% of people in institutionalized settings are dysphagic. There is a need to address dysphagia in ambulatory, acute care, and long-term care settings. C1 [Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr 11G, Madison, WI 53705 USA. [Humbert, Ianessa A.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD 21231 USA. [Robbins, JoAnne] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr 11G, 2500 Overlook Terrace GRECC 11G, Madison, WI 53705 USA. EM jrobbin2@wisc.edu FU NICHD NIH HHS [K12 HD049112]; NIGMS NIH HHS [R01 GM088477] NR 136 TC 39 Z9 49 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 EI 1558-1381 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD NOV PY 2008 VL 19 IS 4 BP 853 EP + DI 10.1016/j.pmr.2008.06.002 PG 16 WC Rehabilitation SC Rehabilitation GA 437NH UT WOS:000265493700012 PM 18940645 ER PT J AU LeMaster, JW Mueller, MJ Reiber, GE Mehr, DR Madsen, RW Conn, VS AF LeMaster, Joseph W. Mueller, Michael J. Reiber, Gayle E. Mehr, David R. Madsen, Richard W. Conn, Vicki S. TI Effect of Weight-Bearing Activity on Foot Ulcer Incidence in People With Diabetic Peripheral Neuropathy: Feet First Randomized Controlled Trial SO PHYSICAL THERAPY LA English DT Article ID 6-MINUTE WALK TEST; ACTIVITY PROMOTION PROGRAM; INCREASE PHYSICAL-ACTIVITY; OLDER-ADULTS; CARDIOVASCULAR-DISEASE; HIGH-RISK; EXERCISE; METAANALYSIS; RELIABILITY; INTENSITY AB Background. Weight-bearing exercise has been contraindicated among people with diabetic peripheral neuropathy (DM+PN). However, recent cohort studies have suggested that daily weight-bearing activity is associated with lower risk for foot ulceration. Objective. The objective of this study was to determine the effect of a lower-extremity exercise and walking intervention program on weight-bearing activity and foot ulcer incidence in people with DM+PN. Design. This was an observer-blinded, 12-month randomized controlled trial Setting. The settings were physical therapy offices in part I of the intervention and the community in part 2 of the intervention. Participants. The participants were 79 individuals with DM+PN who were randomly assigned either to a control group (n=38) or an intervention group (n=41) group. Intervention. Intervention components included leg strengthening and balance exercises; a graduated, self-monitored walking program (part 1); and motivational telephone calls every 2 weeks (part 2). Both groups received diabetic foot care education, regular foot care, and 8 sessions with a physical therapist. Measurements. Total and exercise bout-related daily steps at baseline and at 3, 6, and 12 months were measured by accelerometers. Foot lesions/ulcers were photographed and classified by an independent panel of dermatologists. Use of adequate footwear was monitored. Results. At 6 months; bout-related daily steps increased 14% from baseline in the intervention group and decreased 6% from baseline in the control group. Although the groups did not differ statistically in the change in total daily steps, at 12 months steps had decreased by 13% in the control group. Foot ulcer rates did not differ significantly between groups. Conclusion. Promoting weight-bearing activity did not lead to significant increases in foot ulcers. Weight-bearing activity can be considered following adequate assessment and counseling of patients with DM+PN. C1 [LeMaster, Joseph W.; Mehr, David R.] Univ Missouri, Sch Med, Dept Family & Community Med, Columbia, MO 65212 USA. [Mueller, Michael J.] Washington Univ, Sch Med, Program Phys Therapy, St Louis, MO USA. [Mueller, Michael J.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO USA. [Reiber, Gayle E.] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv & Epidemiol, Seattle, WA 98195 USA. [Madsen, Richard W.] Univ Missouri, Dept Stat, Columbia, MO 65211 USA. [Conn, Vicki S.] Univ Missouri, Sinclair Sch Nursing, Columbia, MO 65211 USA. [Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP LeMaster, JW (reprint author), Univ Missouri, Sch Med, Dept Family & Community Med, MA306-K Med Sci Bldg,DC032-00, Columbia, MO 65212 USA. EM lemasterj@health.missouri.edu OI Conn, Vicki/0000-0003-2404-6575 FU Robert Wood Johnson Foundation FX This study was funded by the Robert Wood Johnson Foundation Generalist Physician Faculty Scholars program. This material is the result of work supported with resources and the use of facilities at the University of Missouri Health Care System, the Harry S Truman Memorial Veterans' Hospital, and the VA Puget Sound Health Care System. NR 62 TC 46 Z9 48 U1 3 U2 16 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD NOV PY 2008 VL 88 IS 11 BP 1385 EP 1398 DI 10.2522/ptj.20080019 PG 14 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 369UC UT WOS:000260718400012 PM 18801859 ER PT J AU Galletti, R Denoux, C Gambetta, S Dewdney, J Ausubel, FM De Lorenzo, G Ferrari, S AF Galletti, Roberta Denoux, Carine Gambetta, Stefano Dewdney, Julia Ausubel, Frederick M. De Lorenzo, Giulia Ferrari, Simone TI The AtrbohD-Mediated Oxidative Burst Elicited by Oligogalacturonides in Arabidopsis Is Dispensable for the Activation of Defense Responses Effective against Botrytis cinerea SO PLANT PHYSIOLOGY LA English DT Article ID HOST-PATHOGEN INTERACTIONS; SYSTEMIC ACQUIRED-RESISTANCE; BERBERINE BRIDGE ENZYME; REACTIVE OXYGEN; SALICYLIC-ACID; HYDROGEN-PEROXIDE; DISEASE-RESISTANCE; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; PLANT DEFENSE AB Oligogalacturonides (OGs) are endogenous elicitors of defense responses released after partial degradation of pectin in the plant cell wall. We have previously shown that, in Arabidopsis (Arabidopsis thaliana), OGs induce the expression of PHYTOALEXIN DEFICIENT3 (PAD3) and increase resistance to the necrotrophic fungal pathogen Botrytis cinerea independently of signaling pathways mediated by jasmonate, salicylic acid, and ethylene. Here, we illustrate that the rapid induction of the expression of a variety of genes by OGs is also independent of salicylic acid, ethylene, and jasmonate. OGs elicit a robust extracellular oxidative burst that is generated by the NADPH oxidase AtrbohD. This burst is not required for the expression of OG-responsive genes or for OG-induced resistance to B. cinerea, whereas callose accumulation requires a functional AtrbohD. OG-induced resistance to B. cinerea is also unaffected in powdery mildew resistant4, despite the fact that callose accumulation was almost abolished in this mutant. These results indicate that the OG-induced oxidative burst is not required for the activation of defense responses effective against B. cinerea, leaving open the question of the role of reactive oxygen species in elicitor-mediated defense. C1 [Galletti, Roberta; De Lorenzo, Giulia; Ferrari, Simone] Univ Roma La Sapienza, Dipartimento Biol Vegetale, I-500185 Rome, Italy. [Gambetta, Stefano] Univ Padua, Dipartimento Terr & Sistemi Agroforestali, I-35020 Legnaro, Italy. [Denoux, Carine; Dewdney, Julia; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Denoux, Carine; Dewdney, Julia; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ferrari, S (reprint author), Univ Roma La Sapienza, Dipartimento Biol Vegetale, I-500185 Rome, Italy. EM simone.ferrari@uniroma1.it RI De Lorenzo, Giulia/F-5475-2013; OI De Lorenzo, Giulia/0000-0002-1707-5418; Galletti, Roberta/0000-0001-8299-7649 FU Ministero dell'Universita e della Ricerca [PRIN2006, PRIN 2005]; European Union [23044]; ERA-NET Plant Genomics [RBER063SN4]; National Institutes of Health [GM48707]; National Science Foundation [DBI-0114783] FX This work was supported by the Ministero dell'Universita e della Ricerca (grant no. PRIN2006), by the European Union (grant no. 23044 ["Nutra-Snacks"] to S. F.), by the Ministero dell'Universita e della Ricerca (grant no. PRIN 2005) and ERA-NET Plant Genomics (grant no. RBER063SN4) to G. D. L., and by the National Institutes of Health (grant no. GM48707) and the National Science Foundation (grant no. DBI-0114783) to F. M. A. NR 83 TC 105 Z9 111 U1 0 U2 21 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD NOV PY 2008 VL 148 IS 3 BP 1695 EP 1706 DI 10.1104/pp.108.127845 PG 12 WC Plant Sciences SC Plant Sciences GA 369UN UT WOS:000260719500041 PM 18790995 ER PT J AU Carlson, JM Brumme, ZL Rousseau, CM Brumme, CJ Matthews, P Kadie, C Mullins, JI Walker, BD Harrigan, PR Goulder, PJR Heckerman, D AF Carlson, Jonathan M. Brumme, Zabrina L. Rousseau, Christine M. Brumme, Chanson J. Matthews, Philippa Kadie, Carl Mullins, James I. Walker, Bruce D. Harrigan, P. Richard Goulder, Philip J. R. Heckerman, David TI Phylogenetic Dependency Networks: Inferring Patterns of CTL Escape and Codon Covariation in HIV-1 Gag SO PLOS COMPUTATIONAL BIOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; STRUCTURALLY CONSTRAINED EPITOPE; INFORMATION-THEORETIC ANALYSIS; WHOLE-GENOME ASSOCIATION; MAXIMUM-LIKELIHOOD; VIRAL LOAD; POPULATION-STRUCTURE; LYMPHOCYTE ESCAPE; COMPENSATORY MUTATION AB HIV avoids elimination by cytotoxic T-lymphocytes (CTLs) through the evolution of escape mutations. Although there is mounting evidence that these escape pathways are broadly consistent among individuals with similar human leukocyte antigen (HLA) class I alleles, previous population-based studies have been limited by the inability to simultaneously account for HIV codon covariation, linkage disequilibrium among HLA alleles, and the confounding effects of HIV phylogeny when attempting to identify HLA-associated viral evolution. We have developed a statistical model of evolution, called a phylogenetic dependency network, that accounts for these three sources of confounding and identifies the primary sources of selection pressure acting on each HIV codon. Using synthetic data, we demonstrate the utility of this approach for identifying sites of HLA-mediated selection pressure and codon evolution as well as the deleterious effects of failing to account for all three sources of confounding. We then apply our approach to a large, clinically-derived dataset of Gag p17 and p24 sequences from a multicenter cohort of 1144 HIV-infected individuals from British Columbia, Canada (predominantly HIV-1 clade B) and Durban, South Africa (predominantly HIV-1 clade C). The resulting phylogenetic dependency network is dense, containing 149 associations between HLA alleles and HIV codons and 1386 associations among HIV codons. These associations include the complete reconstruction of several recently defined escape and compensatory mutation pathways and agree with emerging data on patterns of epitope targeting. The phylogenetic dependency network adds to the growing body of literature suggesting that sites of escape, order of escape, and compensatory mutations are largely consistent even across different clades, although we also identify several differences between clades. As recent case studies have demonstrated, understanding both the complexity and the consistency of immune escape has important implications for CTL-based vaccine design. Phylogenetic dependency networks represent a major step toward systematically expanding our understanding of CTL escape to diverse populations and whole viral genes. C1 [Carlson, Jonathan M.; Kadie, Carl; Heckerman, David] Microsoft Res, eSci Grp, Redmond, WA USA. [Carlson, Jonathan M.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. [Brumme, Zabrina L.; Brumme, Chanson J.; Walker, Bruce D.; Goulder, Philip J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Rousseau, Christine M.; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Matthews, Philippa; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Nuffield Dept Med, Oxford, England. [Mullins, James I.] Univ Washington, Dept Med, Seattle, WA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Harrigan, P. Richard] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Harrigan, P. Richard] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Goulder, Philip J. R.] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Durban, South Africa. RP Carlson, JM (reprint author), Microsoft Res, eSci Grp, Redmond, WA USA. EM carlson@microsoft.com; heckerma@microsoft.com OI Matthews, Philippa/0000-0002-4036-4269; Brumme, Chanson/0000-0003-2722-5288 FU Microsoft Research FX This work was supported by Microsoft Research. NR 109 TC 75 Z9 76 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD NOV PY 2008 VL 4 IS 11 AR e1000225 DI 10.1371/journal.pcbi.1000225 PG 23 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 380QR UT WOS:000261480800017 PM 19023406 ER PT J AU Ch'ng, Q Sieburth, D Kaplan, JM AF Ch'ng, QueeLim Sieburth, Derek Kaplan, Joshua M. TI Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan SO PLOS GENETICS LA English DT Article ID GATED CALCIUM-CHANNEL; DENSE-CORE VESICLE; CAENORHABDITIS-ELEGANS; C-ELEGANS; ACTIVE ZONE; NEUROTRANSMITTER RELEASE; ACETYLCHOLINE-RELEASE; PLASMA-MEMBRANE; LIPRIN-ALPHA; RNAI SCREEN AB Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling. C1 [Ch'ng, QueeLim; Sieburth, Derek; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ch'ng, Q (reprint author), Kings Coll London, Ctr Dev Neurobiol, MRC, London WC2R 2LS, England. EM queelim@kcl.ac.uk; kaplan@molbio.mgh.harvard.edu RI Ch'ng, QueeLim/C-5348-2009 OI Ch'ng, QueeLim/0000-0003-1941-3828 FU Jane Coffin Childs Memorial Postdoctoral Fellowship; The Harold Whitworth Pierce Charitable Trust, Boston; Damon Runyon Cancer Research Foundation; National Institutes of Health FX This work was supported by postdoctoral fellowships from the Jane Coffin Childs Memorial Postdoctoral Fellowship (QC), The Harold Whitworth Pierce Charitable Trust, Boston, MA (QC), the Damon Runyon Cancer Research Foundation (DS) and by grants from the National Institutes of Health (JMK). NR 84 TC 43 Z9 77 U1 0 U2 4 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 NOV PY 2008 VL 4 IS 11 AR e1000283 DI 10.1371/journal.pgen.1000283 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 380QT UT WOS:000261481000037 PM 19043554 ER PT J AU Choy, E Yelensky, R Bonakdar, S Plenge, RM Saxena, R De Jager, PL Shaw, SY Wolfish, CS Slavik, JM Cotsapas, C Rivas, M Dermitzakis, ET Cahir-McFarland, E Kieff, E Hafler, D Daly, MJ Altshuler, D AF Choy, Edwin Yelensky, Roman Bonakdar, Sasha Plenge, Robert M. Saxena, Richa De Jager, Philip L. Shaw, Stanley Y. Wolfish, Cara S. Slavik, Jacqueline M. Cotsapas, Chris Rivas, Manuel Dermitzakis, Emmanouil T. Cahir-McFarland, Ellen Kieff, Elliott Hafler, David Daly, Mark J. Altshuler, David TI Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CISPLATIN-INDUCED CYTOTOXICITY; HAPLOTYPE MAP; COPY NUMBER; VARIANTS; CONTRIBUTE; RISK; LOCI; SUSCEPTIBILITY; PHENOTYPES AB Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance-i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels) than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding. C1 [Choy, Edwin; Yelensky, Roman; Bonakdar, Sasha; Plenge, Robert M.; Saxena, Richa; De Jager, Philip L.; Shaw, Stanley Y.; Wolfish, Cara S.; Cotsapas, Chris; Rivas, Manuel; Hafler, David; Daly, Mark J.; Altshuler, David] Broad Inst MIT & Harvard, Cambridge, MA USA. [Choy, Edwin; Yelensky, Roman; Plenge, Robert M.; Saxena, Richa; Cotsapas, Chris; Daly, Mark J.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Choy, Edwin] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Choy, Edwin; Yelensky, Roman; Plenge, Robert M.; Saxena, Richa; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yelensky, Roman] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [De Jager, Philip L.; Wolfish, Cara S.; Slavik, Jacqueline M.; Hafler, David] Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Boston, MA 02115 USA. [De Jager, Philip L.; Shaw, Stanley Y.; Cahir-McFarland, Ellen; Kieff, Elliott] Harvard Univ, Sch Med, Boston, MA USA. [De Jager, Philip L.] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Slavik, Jacqueline M.] Brigham & Womens Hosp, Biomed Res Inst, Boston, MA 02115 USA. [Cotsapas, Chris; Daly, Mark J.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rivas, Manuel] MIT, Dept Math, Cambridge, MA 02139 USA. [Dermitzakis, Emmanouil T.] Wellcome Trust Sanger Inst, Cambridge, England. [Cahir-McFarland, Ellen; Kieff, Elliott] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Cahir-McFarland, Ellen; Kieff, Elliott] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Choy, E (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; Dermitzakis, Emmanouil/B-7687-2013; OI Altshuler, David/0000-0002-7250-4107; Choy, Edwin/0000-0001-9896-8084 FU SPARC award of the Broad Institute of Harvard; MIT FX This work was supported by the SPARC award of the Broad Institute of Harvard and MIT. NR 43 TC 147 Z9 149 U1 0 U2 11 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 NOV PY 2008 VL 4 IS 11 AR e1000287 DI 10.1371/journal.pgen.1000287 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 380QT UT WOS:000261481000040 PM 19043577 ER PT J AU Fukazawa, A Alonso, C Kurachi, K Gupta, S Lesser, CF McCormick, BA Reinecker, HC AF Fukazawa, Atsuko Alonso, Carmen Kurachi, Kiyotaka Gupta, Sonal Lesser, Cammie F. McCormick, Beth Ann Reinecker, Hans-Christian TI GEF-H1 Mediated Control of NOD1 Dependent NF-kappa B Activation by Shigella Effectors SO PLOS PATHOGENS LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; NUCLEOTIDE EXCHANGE FACTOR; III SECRETION APPARATUS; TOLL-LIKE RECEPTOR-4; WEIGHT GTPASE RHOA; ACTIN CYTOSKELETON; TIGHT JUNCTIONS; BACTERIAL LIPOPOLYSACCHARIDE; PARACELLULAR PERMEABILITY; GENE-TRANSCRIPTION AB Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-kappa B activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappa B activation by H-Ala-Dc-gamma Glu-DAP (gamma TriDAP). GEF-H1 is essential for NF-kappa B activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens. C1 [Fukazawa, Atsuko; Alonso, Carmen; Kurachi, Kiyotaka; Gupta, Sonal; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. [Fukazawa, Atsuko; Alonso, Carmen; Kurachi, Kiyotaka; Gupta, Sonal; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Fukazawa, Atsuko; Alonso, Carmen; Kurachi, Kiyotaka; Gupta, Sonal; Lesser, Cammie F.; McCormick, Beth Ann; Reinecker, Hans-Christian] Harvard Univ, Sch Med, Boston, MA USA. [Lesser, Cammie F.] Massachusetts Gen Hosp, Dept Microbiol & Mol Genet, Boston, MA 02114 USA. [Lesser, Cammie F.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [McCormick, Beth Ann] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. RP Fukazawa, A (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. EM hans-christian_reinecker@hms.harvard.edu RI Alonso-Cotoner, Carmen/N-7057-2014 OI Alonso-Cotoner, Carmen/0000-0002-3483-2919 FU NIH/NIDDK [R01 DK068181, P01 DK003506-20, DK56754]; Spanish Gastroenterological Association; American Gastroenterological Associations (Jon Isenberg International Scholar Award) FX This work was supported by NIH/NIDDK R01 DK068181 (H.C.R.), NIH/NIDDK P01 DK003506-20 (H.C.R. and B.A.M.), and NIH/NIDDK DK56754 (B.A.M). C.A. was supported by a postdoctoral fellowship from the Spanish Gastroenterological Association and the American Gastroenterological Associations (Jon Isenberg International Scholar Award). NR 58 TC 53 Z9 55 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2008 VL 4 IS 11 AR e1000228 DI 10.1371/journal.ppat.1000228 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 380QV UT WOS:000261481200029 PM 19043560 ER PT J AU Shin, S Case, CL Archer, KA Nogueira, CV Kobayashi, KS Flavell, RA Roy, CR Zamboni, DS AF Shin, Sunny Case, Christopher L. Archer, Kristina A. Nogueira, Catarina V. Kobayashi, Koichi S. Flavell, Richard A. Roy, Craig R. Zamboni, Dario S. TI Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila SO PLOS PATHOGENS LA English DT Article ID NF-KAPPA-B; INNATE IMMUNE-RESPONSES; PORE-FORMING TOXINS; INTRACELLULAR GROWTH; BACTERIAL PEPTIDOGLYCAN; PHAGOSOME TRAFFICKING; MACROPHAGE APOPTOSIS; LEGIONNAIRES-DISEASE; PATHOGEN RECOGNITION; EPITHELIAL-CELLS AB The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-kappa B activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria. C1 [Shin, Sunny; Case, Christopher L.; Archer, Kristina A.; Nogueira, Catarina V.; Roy, Craig R.; Zamboni, Dario S.] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06520 USA. [Archer, Kristina A.; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Nogueira, Catarina V.] Univ Porto, Inst Ciencias Biomed Dr Abel Salazar, P-4100 Oporto, Portugal. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Sect Canc Immunol & AIDS, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Shin, S (reprint author), Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06520 USA. EM craig.roy@yale.edu RI Zamboni, Dario/D-3024-2012; OI Zamboni, Dario/0000-0002-7856-7512; Roy, Craig/0000-0003-4490-440X FU NIH [R01 AI04877]; National Science Foundation predoctoral fellowships; NRSA [T32 AI7019-29]; Cancer Research Institute FX This work was supported by NIH grant R01 AI04877 ( C. R. R.), National Science Foundation predoctoral fellowships ( K. A. A. and C. L. C.), NIH Ruth L. Kirschstein NRSA T32 AI7019-29 (S. S.), and the Irvington Institute Postdoctoral Fellowship Program of the Cancer Research Institute (S. S.). NR 70 TC 80 Z9 80 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2008 VL 4 IS 11 AR e1000220 DI 10.1371/journal.ppat.1000220 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 380QV UT WOS:000261481200024 PM 19043549 ER PT J AU Sui, JH Aird, DR Tamin, A Murakami, A Yan, MY Yammanuru, A Jing, HQ Kan, B Liu, X Zhu, Q Yuan, QA Adams, GP Bellini, WJ Xu, JG Anderson, LJ Marasco, WA AF Sui, Jianhua Aird, Daniel R. Tamin, Azaibi Murakami, Akikazu Yan, Meiying Yammanuru, Anuradha Jing, Huaiqi Kan, Biao Liu, Xin Zhu, Quan Yuan, Qing-an Adams, Gregory P. Bellini, William J. Xu, Jianguo Anderson, Larry J. Marasco, Wayne A. TI Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway SO PLOS PATHOGENS LA English DT Article ID ACUTE RESPIRATORY SYNDROME; HUMAN MONOCLONAL-ANTIBODY; ANGIOTENSIN-CONVERTING ENZYME-2; SOMATIC HYPERMUTATION; POTENT NEUTRALIZATION; STRUCTURAL BASIS; B-CELLS; RECEPTOR; PROTEIN; BATS AB Phylogenetic analyses have provided strong evidence that amino acid changes in spike ( S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous-and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase ( AID) "hot spot'' in a light chain CDR ( complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution. C1 [Sui, Jianhua; Aird, Daniel R.; Murakami, Akikazu; Yammanuru, Anuradha; Liu, Xin; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Tamin, Azaibi; Bellini, William J.; Anderson, Larry J.] Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. [Yan, Meiying; Jing, Huaiqi; Kan, Biao; Xu, Jianguo] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China. [Yan, Meiying; Jing, Huaiqi; Kan, Biao; Xu, Jianguo] Chinese Ctr Dis Control & Prevent, Natl Inst Communicable Dis Control & Prevent, Beijing, Peoples R China. [Yuan, Qing-an; Adams, Gregory P.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. RP Sui, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Jianhua_sui@dfci.harvard.edu; Wayne_marasco@dfci.harvard.edu OI SUI, JIANHUA/0000-0002-1272-9662 FU National Foundation for Cancer Research FX We thank Dr. Wenhui Li for helpful discussion and critical review of the manuscript. We also thank the National Foundation for Cancer Research for financial support in purchasing the FACS Calibur used for flow cytometric analysis performed in this study. NR 41 TC 22 Z9 24 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2008 VL 4 IS 11 AR e1000197 DI 10.1371/journal.ppat.1000197 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 380QV UT WOS:000261481200003 PM 18989460 ER PT J AU Lesser, I Zisook, S Flores, D Sciolla, A Wisniewski, S Cook, I Epstein, M Rosales, A Gonzalez, C Trivedi, M Luther, J Alpert, J Rush, AJ AF Lesser, Ira Zisook, Sidney Flores, Deborah Sciolla, Andres Wisniewski, Stephen Cook, Ian Epstein, Marcy Rosales, Aurora Gonzalez, Carlos Trivedi, Madhukar Luther, James Alpert, Jonathan Rush, A. John TI Depression Outcomes of Spanish-and English-Speaking Hispanic Outpatients in STAR*D SO PSYCHIATRIC SERVICES LA English DT Article ID PRIMARY-CARE PATIENTS; MENTAL-HEALTH-SERVICES; ILLNESS RATING-SCALE; QUALITY-OF-LIFE; REPORT QIDS-SR; UNITED-STATES; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; ETHNIC-DIFFERENCES; MEXICAN-AMERICANS AB Objective: This secondary data analysis from the Sequenced Treatment Alternatives to Relieve Depression (STAR* D) study compared clinical characteristics and outcome after citalopram treatment for Hispanic outpatients whose language preference was English (N= 121) or Spanish (N= 74). Methods: Data for Hispanic outpatients with nonpsychotic major depression were gathered from two STAR* D regional centers. Participants received citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission with a measurement-based care approach, with adjustments symptoms and side effects. Results: Spanish speakers were older, were more likely to be women, were less educated, had lower income, had more medical burden, and were more likely than English speakers to be seen in primary care rather than in psychiatric clinics. Compared with Spanish speakers, English speakers had more previous suicide attempts and more family history of mood disorders. The groups did not differ in a clinically meaningful way in severity of depression. Before adjustment for baseline differences, Spanish-speaking participants had lower rates of and slower times to remission and response compared with English speakers. After adjustment for baseline variables, these differences were no longer significant. Relapse rates did not differ between groups. Conclusions: Compared with English-speaking Hispanic patients, Spanish-speaking Hispanic patients may have a less robust response to antidepressants. The reasons for this are not clear but may include more disadvantaged social status. The degree to which these results can be generalized to other Hispanic populations or to other non-English-speaking groups remains to be seen. (Psychiatric Services 59:1273-1284, 2008) C1 [Lesser, Ira; Flores, Deborah; Epstein, Marcy; Rosales, Aurora] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. [Lesser, Ira; Flores, Deborah; Epstein, Marcy; Rosales, Aurora] Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Cook, Ian] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Zisook, Sidney; Sciolla, Andres; Gonzalez, Carlos] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Wisniewski, Stephen; Luther, James] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Trivedi, Madhukar] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Alpert, Jonathan] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Rush, A. John] Duke NUS Grad Med Sch, Singapore, Singapore. RP Lesser, I (reprint author), Harbor UCLA Med Ctr, Dept Psychiat, 1000 W Carson St,Box 8, Torrance, CA 90509 USA. EM ilesser@labiomed.org OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health (NIMH) [N01MH- 90003]; Aspect Medical Systems; PamLab; Cyberonics; Eli Lilly and Company; Novartis; Sepracor; AstraZeneca; Bristol-Myers Squibb; Cephalon; FabreKramer Pharmaceuticals; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica; Johnson Johnson; Neuronetics; Pfizer; Targacept; Wyeth-Ayerst Laboratories FX This project was funded under contract N01MH- 90003 from the National Institute of Mental Health (NIMH). The content of this article does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of commercial products or organizations imply endorsement by the U. S. government. The authors acknowledge the editorial support of Jon Kilner, M.S., M.A.; Dr. Lesser is supported by grants from Aspect Medical Systems, and he has spoken for Medical Education Speakers Network. Dr. Zisook has received research support from PamLab and Aspect Medical Systems and has received honoraria from GlaxoSmithKline and AstraZeneca. Dr. Wisniewski is a consultant for Bristol-Myers Squibb and Organon. Dr. Cook has received research support from Aspect Medical Systems, Cyberonics, Eli Lilly and Company, Novartis, and Sepracor. He is a consultant to Scale Venture Partners and is on the speaker's bureau for CME LLC, Medical Education Speakers Network, and Wyeth. Dr. Trivedi receives research support from or is a consultant for AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly and Company, FabreKramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson, Neuronetics, Pfizer, Targacept, and Wyeth-Ayerst Laboratories. The other authors report no competing interests. NR 98 TC 13 Z9 13 U1 9 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2008 VL 59 IS 11 BP 1273 EP 1284 DI 10.1176/appi.ps.59.11.1273 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 366RT UT WOS:000260501800009 PM 18971403 ER PT J AU Paskett, ED Herndon, JE Day, JM Stark, NN Winer, EP Grubbs, SS Pavy, MD Shapiro, CL List, MA Hensley, ML Naughton, MA Komblith, AB Habin, KR Fleming, GF Bittoni, MA AF Paskett, Electra D. Herndon, James E., II Day, Jeannette M. Stark, Nancy N. Winer, Eric P. Grubbs, Stephen S. Pavy, Michael D. Shapiro, Charles L. List, Marcy A. Hensley, Martee L. Naughton, Michelle A. Komblith, Alice B. Habin, Karleen R. Fleming, Gini F. Bittoni, Marisa A. CA Canc & Leukemia Grp B TI Applying a conceptual model for examining health-related quality of life in long-term breast cancer survivors: CALGB study 79804 SO PSYCHO-ONCOLOGY LA English DT Article; Proceedings Paper CT 1st Cancer Survivorship Conference CY JUN 02-04, 2002 CL Washington, DC SP NCI, Amer Canc Soc DE cancer; oncology; breast cancer survivor; quality of life; health behaviors ID SOCIAL SUPPORT SURVEY; ADJUVANT CHEMOTHERAPY; PSYCHOLOGICAL DISTRESS; DOSE INTENSITY; WOMEN; FATIGUE; CARCINOMA; SYMPTOMS; THERAPY; RISK AB Objectives: The Survivor's Health and Reaction study used a quality-of-life model adapted for cancer survivors by Dow and colleagues to identify factors related to global health-related quality of life (HRQL) and to document the prevalence of problems and health-oriented behaviors in a follow-up study of breast cancer patients who participated in CALGB 8541. Methods: A total of 245 survivors (78% of those invited) who were 9.4-16.5 years Post-diagnosis completed surveys that inquired about current HRQL, economic, spiritual, physical and psychosocial concerns, and health-oriented behaviors (e.g. smoking, exercise, and supplement use). A regression model was developed to examine factors related to global HRQL across all domains. Results: The regression model revealed that decreased energy levels (odds ratio (OR) = 1.05, 95% confidence interval (CI): 1.03, 1.07), having heart disease (OR = 5.01, 95% CI: 1.39, 18.1), having two or more co-morbidities (OR= 2.39, 95% CI: 1.10, 5.0), and lower social support (OR= 1.03, 95% CI: 1.02, 1.05) were associated with lower global HRQL. Factors related to psychological, spiritual, and economic domains were not predictive of global HRQL. Regarding lifestyle changes, some women reported engaging in health-oriented behaviors since their cancer diagnosis, such as improving eating habits (54%), increasing exercise (32%), and reducing/quitting smoking (20%). The most prevalent problems reported by women at follow-up were menopausal symptoms (64%), such as hot flashes and vaginal dryness, osteoporosis (25%), and lymphedema (23%). Conclusion: Suggestions are provided to target interventions, such as provider-based strategies, in order to improve HRQL in long-term breast cancer survivors. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Paskett, Electra D.; Shapiro, Charles L.; Bittoni, Marisa A.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Herndon, James E., II; Day, Jeannette M.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Stark, Nancy N.; Naughton, Michelle A.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Winer, Eric P.; Komblith, Alice B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Grubbs, Stephen S.] Delaware Christiana Core CCOP, Helen F Graham Canc Ctr, Newark, DE USA. [Pavy, Michael D.] SE Canc Control Consortium Inc CCOP, Goldsboro, NC USA. [List, Marcy A.; Fleming, Gini F.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. [Hensley, Martee L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Habin, Karleen R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Paskett, ED (reprint author), Ohio State Univ, Ctr Comprehens Canc, 320 W 10th Ave,Starling Loving Hall A356, Columbus, OH 43210 USA. EM electra.paskett@osumc.edu FU NCI NIH HHS [U10 CA077658, CA03927, CA12449, CA32291, CA33601, CA41287, CA45418, CA45808, CA57707, CA77651, CA77658, CA79883, U10 CA003927, U10 CA032291, U10 CA033601, U10 CA041287, U10 CA045418, U10 CA045808, U10 CA077651]; NIA NIH HHS [AG16602] NR 62 TC 17 Z9 17 U1 6 U2 15 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD NOV PY 2008 VL 17 IS 11 BP 1108 EP 1120 DI 10.1002/pon.1329 PG 13 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 375PC UT WOS:000261124800006 PM 18314912 ER PT J AU Ottowitz, WE Siedlecki, KL Lindquist, MA Dougherty, DD Fischman, AJ Hall, JE AF Ottowitz, William E. Siedlecki, Karen L. Lindquist, Martin A. Dougherty, Darin D. Fischman, Alan J. Hall, Janet E. TI Evaluation of prefrontal-hippocampal effective connectivity following 24 hours of estrogen infusion: An FDG-PET study SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Effective connectivity; Estradiol; Neural networks; Depression; Verbal memory; Postmenopausal women ID POSITRON-EMISSION-TOMOGRAPHY; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; GONADAL-STEROIDS; MENSTRUAL-CYCLE; BRAIN ACTIVITY; CONTROL-SYSTEM; SPINE DENSITY; PLASTICITY; BEHAVIOR AB Although several functional neuroimaging studies have addressed the relevance of hormones to cerebral function, none have evaluated the effects of hormones on network effective connectivity. Since estrogen enhances synaptic connectivity and has been shown to drive activity across neural systems, and because the hippocampus and prefrontal cortex (PFC) are putative targets for the effects of estrogen, we hypothesized that effective connectivity between these regions would be enhanced by an estrogen challenge. In order to test this hypothesis, FDG-PET scans were collected in eleven postmenopausal women at baseline and 24 h after a graded estrogen infusion. Subtraction analysis (SA) was conducted to identify sites of increased cerebral glucose uptake (CMRglc) during estrogen infusion. The lateral PFC and hippocampus were a priori sites for activation; SA identified the right superior frontal gyrus (RSFG; MNI coordinates 18, 60, 28) (SPM2, Wellcome Dept. of Cognitive Neurology, London, UK) as a site of increased CMRglc during estrogen infusion relative to baseline. Omnibus covariate analysis conducted relative to the RSFG identified the right hippocampus (MNI coordinates: 32, -32, -6) and right middle frontal gyrus (RMFG; MNI coordinates: 40, 22, 52) as sites of covariance. Path analysis (Amos 5.0 software) revealed that the path coefficient for the RSFG to RHIP path differed from zero only during E2 infusion (p < 0.05); moreover, the magnitude of the path coefficient for the RHIP to RMFG path showed a significant further increase during the estrogen infusion condition relative to baseline [Delta chi(2) = 4.05, Delta d.f. = 1, p = 0.044]. These findings are consistent with E2 imparting a stimulatory effect on effective connectivity within prefrontal-hippocampal circuitry. This holds mechanistic significance for resting state network interactions and may hold implications for mood and cognition. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Ottowitz, William E.] Columbia Univ, Dept Stat, Grad Sch Arts & Sci, New York, NY 10027 USA. [Siedlecki, Karen L.] Columbia Univ, Coll Phys & Surg, Taub Inst, New York, NY 10032 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp East, Dept Psychiat, Psychiat Neurosci Program, Charlestown, MA 02129 USA. [Fischman, Alan J.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. [Hall, Janet E.] Massachusetts Gen Hosp, Dept Med, Div Reprod Endocrinol, Boston, MA 02114 USA. RP Ottowitz, WE (reprint author), Columbia Univ, Dept Stat, Grad Sch Arts & Sci, 1255 Amsterdam Ave,Room 1005,MC 4690, New York, NY 10027 USA. EM weo2101@columbia.edu FU NIH and NIMH [R01 AG13241, K24HD01290, M01 RR01066, T32MH020004-09] FX The authors gratefully acknowledge support from NIH and NIMH for Grants R01 AG13241, K24HD01290, M01 RR01066, and T32MH020004-09. We also thank Steve Weiss for his technical assistance regarding scan acquisition. NR 43 TC 14 Z9 14 U1 0 U2 4 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 NOV PY 2008 VL 33 IS 10 BP 1419 EP 1425 DI 10.1016/j.psyneuen.2008.09.013 PG 7 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 385ZY UT WOS:000261853300013 PM 18977091 ER PT J AU Putnam, KM Pizzagalli, DA Gooding, DC Kalin, NH Davidson, RJ AF Putnam, Katherine M. Pizzagalli, Diego A. Gooding, Diane C. Kalin, Ned H. Davidson, Richard J. TI Neural activity and diurnal variation of cortisol: Evidence from brain electrical tomography analysis and relevance to anhedonia SO PSYCHOPHYSIOLOGY LA English DT Review DE Electroencephalography (EEG); Anhedonia; Cortisol; Stress; Prefrontal cortex; Low resolution electromagnetic tomography (LORETA) ID RESOLUTION ELECTROMAGNETIC TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; PITUITARY-ADRENAL AXIS; EEG-ALPHA ASYMMETRY; CEREBRAL-BLOOD-FLOW; ORBITOFRONTAL CORTEX; SALIVARY CORTISOL; FRONTAL-CORTEX; FUNCTIONAL NEUROANATOMY; MOMENTARY ASSESSMENT AB The medial prefrontal cortex (mPFC), hippocampus, and amygdala are implicated in the regulation of affect and physiological processes, including hypothalamic-pituitary-adrenal (HPA) axis function. Anhedonia is likely associated with dysregulation of these processes. Dense-array resting electroencephalographic and cortisol were obtained from healthy and anhedonic groups. Low-resolution electromagnetic tomography was used to compute intracerebral current density. For the control group, voxelwise analyses found a relationship between current density in beta and gamma bands and steeper cortisol slope (indicative of more adaptive HPA axis functioning) in regions of the hippocampus, parahippocampal gyrus, and mPFC. For the anhedonic group, the mPFC finding was absent. Anhedonia may be characterized by disruptions of mPFC-mediated neuroendocrine regulation, which could constitute a vulnerability to the development of stress- related disorders. C1 [Putnam, Katherine M.] Boston Univ, Natl Ctr PTSD, VA Boston Healthcare Syst, Sch Med,Dept Psychiat, Boston, MA 02130 USA. [Pizzagalli, Diego A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Gooding, Diane C.; Davidson, Richard J.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. [Gooding, Diane C.; Kalin, Ned H.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Davidson, Richard J.] Univ Wisconsin, Waisman Ctr, Keck Ctr Brain Imaging & Behav, Madison, WI 53706 USA. RP Putnam, KM (reprint author), Boston Univ, Natl Ctr PTSD, VA Boston Healthcare Syst, Sch Med,Dept Psychiat, 150 S Huntington Ave, Boston, MA 02130 USA. EM katherine.putnam@va.gov FU NIH [T32-MH18931, P50-MH52354, P50-MH069315, R37-MH43454]; National Alliance for Research in Depression and Schizophrenia (NARSAD); NIMH [P50-MH52354, R01MH68376]; NCCAM [R21 AT002974]; Wisconsin Alumni Research Foundation FX The authors thank Lauren McSweeney and Colin Sauder for assistance on manuscript preparation and Avram Holmes for performing the AlphaSim simulations reported in this article. This research was supported by an NIH training grant, T32-MH18931, and a Young Investigator award from the National Alliance for Research in Depression and Schizophrenia (NARSAD) awarded to K. M. P. and NIH grants P50-MH52354, P50-MH069315, and R37-MH43454 awarded to R.J.D. D. A. P. was supported by NIH grants from the NIMH, R01MH68376 and NCCAM R21 AT002974. D. C. G. was supported by a NIMH Supplement for Underrepresented Minorities, P50-MH52354, and a grant from the Wisconsin Alumni Research Foundation. NR 102 TC 8 Z9 8 U1 7 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2008 VL 45 IS 6 BP 886 EP 895 DI 10.1111/j.1469-8986.2008.00697.x PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 361AP UT WOS:000260100200002 PM 18823425 ER PT J AU Chou, CP Levenson, RB Elsayes, KM Lin, YH Fu, TY Chiu, YS Huang, JS Pan, HB AF Chou, Chen-Pin Levenson, Robin B. Elsayes, Khaled M. Lin, Yih-Huie Fu, Ting-Ying Chiu, You-Shin Huang, Jer-Shyung Pan, Huay-Ben TI Imaging of Female Urethral Diverticulum: An Update SO RADIOGRAPHICS LA English DT Article ID VOIDING CYSTOURETHROGRAPHY; POSITIVE-PRESSURE; DIAGNOSIS; WOMEN; ULTRASONOGRAPHY; URETHROGRAPHY; MANAGEMENT; URETHROSCOPY; SONOGRAPHY; EXPERIENCE C1 [Chou, Chen-Pin; Lin, Yih-Huie; Chiu, You-Shin; Huang, Jer-Shyung; Pan, Huay-Ben] Kaohsiung Vet Gen Hosp, Dept Radiol, Taipei 813, Taiwan. [Chou, Chen-Pin] Kaohsiung Vet Gen Hosp, Inst Clin Med, Taipei 813, Taiwan. Natl Yang Ming Univ, Taipei 813, Taiwan. [Levenson, Robin B.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Elsayes, Khaled M.] Univ Michigan, Dept Radiol, Ctr Hlth, Ann Arbor, MI 48109 USA. [Fu, Ting-Ying] Kaohsiung Vet Gen Hosp, Dept Pathol, Taipei 813, Taiwan. RP Chou, CP (reprint author), Kaohsiung Vet Gen Hosp, Dept Radiol, Taipei 813, Taiwan. EM r2207759@ms19.hinet.net NR 40 TC 23 Z9 24 U1 0 U2 1 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 NOV-DEC PY 2008 VL 28 IS 7 BP 1917 EP 1930 DI 10.1148/rg.287075076 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 371XV UT WOS:000260866900009 PM 19001648 ER PT J AU Gupta, R Cheung, AC Bartling, SH Lisauskas, J Grasruck, M Leidecker, C Schmidt, B Flohr, T Brady, TJ AF Gupta, Rajiv Cheung, Arnold C. Bartling, Soenke H. Lisauskas, Jennifer Grasruck, Michael Leidecker, Christianne Schmidt, Bernhard Flohr, Thomas Brady, Thomas J. TI Flat-Panel Volume CT: Fundamental Principles, Technology, and Applications SO RADIOGRAPHICS LA English DT Article ID CONE-BEAM CT; DETECTOR COMPUTED-TOMOGRAPHY; TEMPORAL BONE; PREOPERATIVE ANATOMY; SURGERY; SPECIMENS; GUIDANCE; SYSTEM; ARM AB Flat-panel volume computed tomography (CT) systems have an innovative design that allows coverage of a large volume per rotation, fluoroscopic and dynamic imaging, and high spatial resolution that permits visualization of complex human anatomy such as fine temporal bone structures and trabecular bone architecture. In simple terms, flat-panel volume CT scanners can be thought of as conventional multidetector CT scanners in which the detector rows have been replaced by an area detector. The flat-panel detector has wide z-axis coverage that enables imaging of entire organs in one axial acquisition. Its fluoroscopic and angiographic capabilities are useful for intraoperative and vascular applications. Furthermore, the high-volume coverage and continuous rotation of the detector may enable depiction of dynamic processes such as coronary blood flow and whole-brain perfusion. Other applications in which flat-panel volume CT may play a role include small-animal imaging, nondestructive testing in animal survival surgeries, and tissue-engineering experiments. Such versatility has led some to predict that flat-panel volume CT will gain importance in interventional and intraoperative applications, especially in specialties such as cardiac imaging, interventional neuroradiology, orthopedics, and otolaryngology. However, the contrast resolution of flat-panel volume CT is slightly inferior to that of multidetector CT, a higher radiation dose is needed to achieve a comparable signal-to-noise ratio, and a slower scintillator results in a longer scanning time. C1 [Gupta, Rajiv; Cheung, Arnold C.; Lisauskas, Jennifer; Brady, Thomas J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bartling, Soenke H.] German Canc Res Ctr, Heidelberg, Germany. [Grasruck, Michael; Leidecker, Christianne; Schmidt, Bernhard; Flohr, Thomas] Siemens Med Solut, Erlangen, Germany. RP Gupta, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders House,FND-2-216, Boston, MA 02114 USA. EM rgupta1@partners.org NR 27 TC 88 Z9 92 U1 0 U2 3 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 NOV-DEC PY 2008 VL 28 IS 7 BP 2009 EP 2022 DI 10.1148/rg.287085004 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 371XV UT WOS:000260866900015 PM 19001655 ER PT J AU Curtin, HD AF Curtin, Hugh D. TI The "Evil Gray": Cancer and Cartilage SO RADIOLOGY LA English DT Editorial Material ID RADIATION-THERAPY; LARYNGEAL-CANCER; INVASION C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Curtin, HD (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. EM hdcurtin@meei.harvard.edu NR 7 TC 4 Z9 4 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2008 VL 249 IS 2 BP 410 EP 412 DI 10.1148/radiol.2492081113 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 362RS UT WOS:000260215400004 PM 18936304 ER PT J AU Sorensen, AG AF Sorensen, A. Gregory TI Perfusion MR Imaging: Moving Forward SO RADIOLOGY LA English DT Editorial Material ID TUMOR GRADE; CONTRAST; STROKE; BRAIN; SURVIVAL; GLIOMAS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. RP Sorensen, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 13th St,Bldg 149,MC 2301, Boston, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu NR 11 TC 15 Z9 15 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 NOV PY 2008 VL 249 IS 2 BP 416 EP 417 DI 10.1148/radiol.2492081429 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 362RS UT WOS:000260215400006 PM 18936306 ER PT J AU Pomerantz, SR AF Pomerantz, Stuart R. TI Net Assets: Primum Non Nocere-Online Radiology Safety Resources SO RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA 02114 USA. RP Pomerantz, SR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, 55 Fruit St,Gray 2-B285, Boston, MA 02114 USA. EM netassets@rsna.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2008 VL 249 IS 2 BP 425 EP 428 DI 10.1148/radiol.2492081422 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 362RS UT WOS:000260215400008 PM 18936308 ER PT J AU Korosoglou, G Shah, S Vonken, EJ Gilson, WD Schar, M Tang, L Kraitchman, DL Boston, RC Sosnovik, DE Weiss, RG Weissleder, R Stuber, M AF Korosoglou, Grigorios Shah, Saurabh Vonken, Evert-Jan Gilson, Wesley D. Schaer, Michael Tang, Lijun Kraitchman, Dara L. Boston, Raymond C. Sosnovik, David E. Weiss, Robert G. Weissleder, Ralph Stuber, Matthias TI Off-Resonance Angiography: A New Method to Depict Vessels-Phantom and Rabbit Studies SO RADIOLOGY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; LYMPH-NODE METASTASES; FLIGHT MR-ANGIOGRAPHY; CONTRAST AGENT; MAGNETIC NANOPARTICLES; INVERSION-RECOVERY; ENHANCEMENT; TIME; VISUALIZATION; ARTERIOGRAPHY AB Purpose: To evaluate the utility of inversion recovery with on-resonant water suppression (IRON) in combination with injection of the long-circulating monocrystalline iron oxide nanoparticle (MION)-47 for contrast material -enhanced magnetic resonance (MR) angiography. Materials and Methods: Experiments were approved by the institutional animal care committee. Eleven rabbits were imaged at baseline before injection of a contrast agent and then serially 5-30 minutes, 2 hours, 1 day, and 3 days after a single intravenous bolus injection of 80 mu mol of MION-47 per kilogram of body weight (n = 6) or 250 mu mol/ kg MION-47 (n = 5). Conventional T1-weighted MR angiography and IRON MR angiography were performed on a clinical 3.0-T imager. Signal-to-noise and contrast-to-noise ratios were measured in the aorta of rabbits in vivo. Venous blood was obtained from the rabbits before and after MION-47 injection for use in phantom studies. Results: In vitro blood that contained MION-47 appeared signal attenuated on T1-weighted angiograms, while characteristic signal-enhanced dipolar fields were observed on IRON angiograms. In vivo, the vessel lumen was signal attenuated on T1-weighted MR angiograms after MION-47 injection, while IRON supported high intravascular contrast by simultaneously providing positive signal within the vessels and suppressing background tissue (mean contrast-tonoise ratio, 61.9 +/- 12.4 [standard deviation] after injection vs 1.1 +/- 0.4 at baseline, P < .001). Contrast-to-noise ratio was higher on IRON MR angiograms than on conventional T1-weighted MR angiograms (9.0 +/- 2.5, P < .001 vs IRON MR angiography) and persisted up to 24 hours after MION-47 injection (76.2 +/- 15.9, P < .001 vs baseline). Conclusion: IRON MR angiography in conjunction with superparamagnetic nanoparticle administration provides high intravascular contrast over a long time and without the need for image subtraction. C1 [Korosoglou, Grigorios; Shah, Saurabh; Vonken, Evert-Jan; Gilson, Wesley D.; Schaer, Michael; Tang, Lijun; Kraitchman, Dara L.; Weiss, Robert G.; Stuber, Matthias] Johns Hopkins Univ Hosp, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Weiss, Robert G.] Johns Hopkins Univ Hosp, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. [Boston, Raymond C.] Univ Penn, Sch Vet Med, Kennett Sq, PA 19348 USA. [Sosnovik, David E.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Stuber, M (reprint author), Johns Hopkins Univ Hosp, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St,Pk Bldg,Room 338, Baltimore, MD 21287 USA. EM mstuber@mri.jhu.edu RI Stuber, Matthias/B-2949-2010; Schar, Michael/C-8087-2015; OI Stuber, Matthias/0000-0001-9843-2028; Schar, Michael/0000-0002-7044-9941 FU NIH [1 K08 EB004922-01, R01 HL084186, R01 HL61912, R24 CA92782] FX Supported by NIH grants 1 K08 EB004922-01, R01 HL084186, R01 HL61912, and R24 CA92782, as well as by the Donald W. Reynolds NR 32 TC 15 Z9 16 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2008 VL 249 IS 2 BP 501 EP 509 DI 10.1148/radiol.2491071706 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 362RS UT WOS:000260215400015 PM 18780823 ER PT J AU Cobb, BL Lessard, CJ Harley, JB Moser, KL AF Cobb, Beth L. Lessard, Christopher J. Harley, John B. Moser, Kathy L. TI Genes and Sjogren's Syndrome SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review DE Sjogren's syndrome; Genetics; HLA; Association ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SINGLE-NUCLEOTIDE POLYMORPHISM; GENOME-WIDE ASSOCIATION; BINDING LECTIN GENE; LYMPHOID TYROSINE PHOSPHATASE; PROMOTER REGION POLYMORPHISMS; JUVENILE IDIOPATHIC ARTHRITIS; EUROPEAN CONSENSUS GROUP; PTPN22 620W ALLELE; CLASS-II GENES AB The evidence for a strong genetic component conferring susceptibility to primary Sjogren's syndrome (SS) is mounting. Several associations with SS have been reported and provide evidence that the HLA region harbors important susceptibility loci and that multiple genes outside the HLA region play a role. Genetic discovery lags behind success observed in related autoimmune diseases. Identifying genetic factors that cause SS will allow more precise definition of pathogenic mechanisms leading to the overall SS phenotype and clinically heterogeneous subsets of patients. Critical opportunities are certain to follow for translation into improved diagnosis and therapies for SS and its spectrum diseases. C1 [Cobb, Beth L.; Lessard, Christopher J.; Harley, John B.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. [Lessard, Christopher J.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. [Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA. RP Moser, KL (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM moserk@omrf.org FU NIH [DE015223, AR42460, AR12253, AR48940, AR62277, RR020143, AI24717]; Department of Veteran Affairs Merit Award (JBH) [AR050782, AR043274]; Alliance for Lupus Research FX Supported by NIH grants DE015223, AR42460, AR12253, AR48940, AR62277, RR020143, AI24717, a Department of Veteran Affairs Merit Award (JBH), AR050782, and AR043274 (KLM) and the Alliance for Lupus Research. NR 150 TC 21 Z9 21 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 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2008 VL 34 IS 4 BP 847 EP + DI 10.1016/j.rdc.2008.08.003 PG 23 WC Rheumatology SC Rheumatology GA 376RD UT WOS:000261199800003 PM 18984408 ER PT J AU Bingham, JT Papannagari, R de Velde, SKV Gross, C Gill, TJ Felson, DT Rubash, HE Li, G AF Bingham, J. T. Papannagari, R. de Velde, S. K. Van Gross, C. Gill, T. J. Felson, D. T. Rubash, H. E. Li, G. TI In vivo cartilage contact deformation in the healthy human tibiofemoral joint SO RHEUMATOLOGY LA English DT Article DE Compartmental cartilage deformation; Knee joint; Biomechanics; Magnetic resonance; Cartilage thickness ID ANTERIOR CRUCIATE LIGAMENT; HUMAN ARTICULAR-CARTILAGE; KNEE-JOINT; PATELLOFEMORAL JOINT; WEIGHT-BEARING; LOWER-LIMB; THICKNESS; KINEMATICS; MRI; MODEL AB Objectives. In vivo cartilage contact deformation is instrumental for understanding human joint function and degeneration. This study measured the total deformation of contacting articular cartilage in the human tibiofemoral joint during in vivo weight-bearing flexion. Methods. Eleven healthy knees were magnetic resonance (MR) scanned and imaged with a dual fluoroscopic system while the subject performed a weight-bearing single-leg lunge. The tibia, femur and associated articulating cartilage were constructed from the MR images and combined with the dual fluoroscopic images to determine in vivo cartilage contact deformation from full extension to 120 degrees of flexion. Results. In both compartments, minimum peak compartmental contact deformation occurred at 30 degrees of flexion (24 +/- 6% medial, 17 +/- 7% lateral) and maximum peak compartmental deformation occurred at 120 degrees of flexion (30 +/- 13% medial, 30 +/- 10% lateral) during the weight-bearing flexion from full extension to 120 degrees. Average medial contact areas and peak contact deformations were significantly greater than lateral compartment values (P < 0.05). In addition, cartilage thickness in regions of contact was on average 1.4- and 1.1-times thicker than the average thickness of the tibial and femoral cartilage surfaces, respectively (P < 0.05). Conclusions. These data may provide base- line knowledge for investigating the effects of various knee injuries on joint contact biomechanics and the aetiology of cartilage degeneration. C1 [Bingham, J. T.; Papannagari, R.; de Velde, S. K. Van; Gross, C.; Gill, T. J.; Rubash, H. E.; Li, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Felson, D. T.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org RI Bingham, Jeffrey/I-6901-2012; OI Bingham, Jeffrey/0000-0002-9590-8526; Felson, David/0000-0002-2668-2447 FU National Institutes of Health [R01-AR052408, R01-AR47785]; Harvard PASTEUR FX We thank Louis DeFrate, Jeremy Moses, Kyung Wook Nha and Meng Li of the MGH Bioengineering Laboratory whose comments and suggestions were invaluable. The technical assistance of Elizabeth Desouza from OR management of MGH was also greatly appreciated.; Funding: This work was supported by a grant from the National Institutes of Health (R01-AR052408) (G. L.), (R01-AR47785) (D. F.), and fellowship support from the Harvard PASTEUR Program (C. G.).; Disclosure statement: The authors have declared no conflicts of interest. NR 51 TC 69 Z9 73 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2008 VL 47 IS 11 BP 1622 EP 1627 DI 10.1093/rheumatology/ken345 PG 6 WC Rheumatology SC Rheumatology GA 361NJ UT WOS:000260134100007 PM 18775967 ER PT J AU Green, MF Penn, DL Bentall, R Carpenter, WT Gaebel, W Gur, RC Kring, AM Park, S Silverstein, SM Heinssen, R AF Green, Michael F. Penn, David L. Bentall, Richard Carpenter, William T. Gaebel, Wolfgang Gur, Ruben C. Kring, Ann M. Park, Sohee Silverstein, Steven M. Heinssen, Robert TI Social Cognition in Schizophrenia: An NIMH Workshop on Definitions, Assessment, and Research Opportunities SO SCHIZOPHRENIA BULLETIN LA English DT Review DE social cognition; schizophrenia; NIMH ID FACIAL-AFFECT RECOGNITION; MEDIAL PREFRONTAL CORTEX; PERSECUTORY DELUSIONS; EMOTION RECOGNITION; SPECTRUM DISORDERS; TRAINING-PROGRAM; MIND DEFICIT; NEURAL BASIS; PERCEPTION; PARANOIA AB Social cognition has become a high priority area for the study of schizophrenia. However, despite developments in this area, progress remains limited by inconsistent terminology and differences in the way social cognition is measured. To address these obstacles, a consensus-building meeting on social cognition in schizophrenia was held at the National Institute of Mental Health in March 2006. Agreement was reached on several points, including definitions of terms, the significance of social cognition for schizophrenia research, and suggestions for future research directions. The importance of translational interdisciplinary research teams was emphasized. The current article presents a summary of these discussions. C1 [Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Penn, David L.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Bentall, Richard] Univ Wales, Sch Psychol, Bangor, Gwynedd, Wales. [Carpenter, William T.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Carpenter, William T.] Vet Adm, VISN 5, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. [Gaebel, Wolfgang] Univ Dusseldorf, Dept Psychiat, D-4000 Dusseldorf, Germany. [Gur, Ruben C.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Kring, Ann M.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Park, Sohee] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Park, Sohee] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37240 USA. [Silverstein, Steven M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. [Silverstein, Steven M.] Univ Med & Dent New Jersey, Univ Behav HealthCare, Piscataway, NJ 08854 USA. [Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu OI Park, Sohee/0000-0003-3797-4776 FU NIMH FX This article presents a summary of the discussion from a workshop supported by the NIMH. The views expressed are those of the authors and do not necessarily reflect the official views of the NIMH, the National Institutes of Health, or any other branch of the US Department of Health and Human Services. NR 101 TC 261 Z9 274 U1 6 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2008 VL 34 IS 6 BP 1211 EP 1220 DI 10.1093/schbul/sbm145 PG 10 WC Psychiatry SC Psychiatry GA 361OI UT WOS:000260136600027 PM 18184635 ER PT J AU Condray, R Yao, JK Steinhauer, SR van Kammen, DP Reddy, RD Morrow, LA AF Condray, Ruth Yao, Jeffrey K. Steinhauer, Stuart R. van Kammen, Daniel P. Reddy, Ravinder D. Morrow, Lisa A. TI Semantic memory in schizophrenia: Association with cell membrane essential fatty acids SO SCHIZOPHRENIA RESEARCH LA English DT Article DE N400; Arachidonic acid; Dopamine; Paranoia; Thought disturbance ID EVENT-RELATED POTENTIALS; SEROTONERGIC RESPONSIVITY; DOPAMINERGIC MODULATION; ORBITOFRONTAL CORTEX; COGNITIVE DYSMETRIA; HUMAN ERYTHROCYTES; DISORDER; LANGUAGE; BRAIN; N400 AB Introduction: Semantic memory and language deficits are associated with schizophrenia. Understanding how these systems operate in this disorder will likely require a multi-factorial model that explains their linkages with cognition and modulation by dopamine. A biological factor that may provide causal convergence for these connections is cell membrane composition and dynamics. Methods: N400 is an electrophysiological measure of semantic memory and language that is sensitive to deficits in schizophrenia. Relationships among N400, cognition, dopamine, and cell membrane polyunsaturated fatty acids (PUFAs) were examined for patients tested under medicated (haloperidol only) and unmedicated (placebo) conditions. Relationships between these factors and clinical symptoms were also evaluated. The sample included 37 male schizophrenia inpatients and 34 male normal controls. The N400 priming effect was measured from visual event-related potentials recorded during a semantic priming-lexical decision task, in which semantic association (related versus unrelated words) and presentation rate (Stimulus Onset Asynchrony/SOAs: 350 and 950 ms) were varied. Results: N400 was associated with cognition (speed, visuoperception, attention) in patients and controls. These relationships were influenced by SOA in both groups, and by pharmacological condition in patients. Levels of total PUFAs and arachidonic acid were associated with N400 in unmedicated patients. Clinical symptoms (paranoia, thought disturbance) were associated with N400, but not with cognition or PUFAs. Conclusions: Results suggest cell membrane fatty acids are associated with semantic memory and language in schizophrenia. Findings also suggest a series of linkages that are modulated by dopamine: cell membrane fatty acids are associated with N400 semantic priming; N400 semantic priming is associated with clinical symptoms. (C) 2008 Published by Elsevier B.V. C1 [Condray, Ruth; Yao, Jeffrey K.; Steinhauer, Stuart R.; Reddy, Ravinder D.; Morrow, Lisa A.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. [Condray, Ruth; Yao, Jeffrey K.; Steinhauer, Stuart R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. [van Kammen, Daniel P.] MRSSI Inc, New York, NY 10016 USA. [van Kammen, Daniel P.] CHDI Inc, Los Angeles, CA 90045 USA. RP Condray, R (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, 3811 OHara St, Pittsburgh, PA 15213 USA. EM condrayr@upmc.edu FU National Institute of Mental Health [MH50631, MH55762, MH44841]; Medical Research Service of the Department of Veterans Affairs; Bataan and Corregidor Medical Fund, Inc.; Veterans Affairs Pittsburgh Healthcare System; Highland Drive Division FX Funding for this work was provided by grants to authors from the National Institute of Mental Health (MH50631, MH55762, MH44841), Medical Research Service of the Department of Veterans Affairs, the Bataan and Corregidor Medical Fund, Inc., and with resources and use of facilities at the Veterans Affairs Pittsburgh Healthcare System, Highland Drive Division. The NIMH and the Medical Research Service of the Department of Veterans Affairs had no further role in the design or conduct of the study, in analyses or interpretation of data, in writing of the reports or in the decision to submit the paper for publication.; This research was supported by the National Institute of Mental Health (ME50631 (RC), MH55762 (SRS), MH44841 (DPvK)), the Medical Research Service of the Department of Veterans Affairs, the Bataan and Corregidor Medical Fund, Inc. (DPvK), and with resources and use of facilities at the Veterans Affairs Pittsburgh Healthcare System, Highland Drive Division. We thank the patients who served as study participants. We are also grateful to a number of individuals who provided valuable contributions to the study, including the clinical and nursing staff of the Veterans Affairs Pittsburgh Healthcare System, Highland Drive Division. The contributions of the anonymous reviewers are also appreciated. NR 82 TC 12 Z9 12 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2008 VL 106 IS 1 SI SI BP 13 EP 28 DI 10.1016/j.schres.2008.03.009 PG 16 WC Psychiatry SC Psychiatry GA 377MY UT WOS:000261256500003 PM 18929465 ER PT J AU O'Halloran, JP Kemp, AS Gooch, KN Harvey, PD Palmer, BW Reist, C Schneider, LS AF O'Halloran, James P. Kemp, Aaron S. Gooch, Kirstan N. Harvey, Philip D. Palmer, Barton W. Reist, Christopher Schneider, Lon S. TI Psychometric comparison of computerized and standard administration of the neurocognitive assessment instruments selected by the CATIE and MATRICS consortia among patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE CMINDS; Neurocognition; Schizophrenia; Computerized Assessment; Concurrent Validity; Reliability ID SAMPLE-SIZE REQUIREMENTS; CLINICAL-TRIALS; COGNITIVE DEFICITS; INTRACLASS CORRELATION; TEST BATTERY; RELIABILITY; VALIDITY; COEFFICIENT; MEDICATIONS; AGREEMENT AB Neurocognitive assessment is an essential component for clinical trials of candidate "cognitive-enhancing" treatments for schizophrenia. However, manual administration of large, paper-based, neurocognitive batteries is often inefficient, error-prone, and inconsistent across multiple sites. Existing computerized testing systems are also limited both in the assessment instruments available and in the range of impairments that can be accommodated with the subject sitting alone at a single display. Therefore, a dual-display computerized testing system was developed, with funding from the National Institute of Mental Health (NDAH), that integrates (rather than replaces) the examiner for computerized administration of standard neurocognitive assessment batteries. Purpose: To compare standard administration versions (SAVs) of tests selected by the NIMH-sponsored CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) and MATRICS (TM) (Measurement and Treatment Research to Improve Cognition in Schizophrenia) consortia, with structurally- and functionally-equivalent, computerized administration versions (CAVs). Method: 116 outpatients with schizophrenia received both the SAVs and CAVs within one week and again, approximately 30 days later. Results: Intraclass Correlation Coefficient (ICC) comparisons between SAVs and CAVs yielded highly significant measures of absolute agreement for all tests, ranging 0.61-0.95. ICCs for test-retest reliability, ranging 0.56-0.94 for SAVs and 0.59-0.98 for CAVs, were also highly significant for both batteries, though significantly higher for CAVs overall. Conclusions: The CAVs of the neurocognitive assessment instruments selected by the CATIE and MATRICS (TM) consortia are substantially equivalent to antecedent SAVs. Importantly, the increased reliability afforded by computerization highlight the potential for increasing power, thereby decreasing sample size requirements, for clinical evaluations of putative "cognitive-enhancing" treatments. (C) 2007 Elsevier B.V. All rights reserved. C1 [O'Halloran, James P.; Kemp, Aaron S.; Gooch, Kirstan N.] NeuroComp Syst Inc, Irvine, CA 92614 USA. [Kemp, Aaron S.; Reist, Christopher] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Harvey, Philip D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Harvey, Philip D.] James J Peters Vet Adm VA Med Ctr, Bronx, NY USA. [Palmer, Barton W.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Palmer, Barton W.] Vet Med Res Fdn, San Diego, CA USA. [Reist, Christopher] VA Long Beach Healthcare Syst, Long Beach, CA USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat Neurol & Gerontol, Los Angeles, CA 90033 USA. RP O'Halloran, JP (reprint author), NeuroComp Syst Inc, 1340 Reynolds Ave,Suite 105, Irvine, CA 92614 USA. EM jpo@neurocomp.com OI Kemp, Aaron/0000-0001-6925-5667 FU NIMH Small Business Innovation Research [R43MH068077-01, R44MH068077-02] FX James P. O'Halloran is the founder and president of NeuroComp Systems, Inc. Kirstan N. Gooch is a full-time employee of NeuroComp, Systems, Inc. Aaron S. Kemp is a paid consultant to NeuroComp Systems, Inc. None of the other authors have any previous or on-going financial arrangements with NeuroComp Systems, Inc., aside from receipt of funding from NIMH for participation in this study as subcontract Pls. NR 38 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2008 VL 106 IS 1 BP 33 EP 41 DI 10.1016/j.schres.2007.11.015 PG 9 WC Psychiatry SC Psychiatry GA 377MY UT WOS:000261256500005 PM 18160262 ER PT J AU Bowie, CR Reichenberg, A McClure, MM Leung, WL Harvey, PD AF Bowie, Christopher R. Reichenberg, Abraham McClure, Margaret M. Leung, Winnie L. Harvey, Philip D. TI Age-associated differences in cognitive performance in older community dwelling schizophrenia patients: Differential sensitivity of clinical neuropsychological and experimental information processing tests SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Neuropsychology; Cognition; Information processing; Aging ID SCHIZOTYPAL PERSONALITY-DISORDER; PREFRONTAL CORTEX DYSFUNCTION; WORKING-MEMORY; WHITE-MATTER; FOLLOW-UP; MULTIPLE-SCLEROSIS; METABOLIC-RATE; DEFICITS; DECLINE; SYMPTOMS AB Cognitive dysfunction is a common feature of schizophrenia and deficits are present before the onset of psychosis, and are moderate to severe by the time of the first episode. Controversy exists over the course of cognitive dysfunction after the first episode. This study examined age-associated differences in performance on clinical neuropsychological (NP) and information processing tasks in a sample of geriatric community living schizophrenia patients (n = 172). Compared to healthy control subjects (n = 70), people with schizophrenia did not differ on NP tests across age groups but showed evidence for age-associated cognitive worsening on the more complex components of an information-processing test. Age-related changes in cognitive function in schizophrenia may be a function of both the course of illness and the processing demands of the cognitive measure of interest. Tests with fixed difficulty, such as clinical NP tests, may differ in their sensitivity from tests for which parametric difficulty manipulations can be performed. (C) 2007 Elsevier B.V. All rights reserved. C1 [Bowie, Christopher R.; Reichenberg, Abraham; McClure, Margaret M.; Leung, Winnie L.; Harvey, Philip D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Bowie, Christopher R.] James J Peters Bronx VA Med Ctr, Bronx, NY 10468 USA. [Reichenberg, Abraham] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [McClure, Margaret M.; Leung, Winnie L.; Harvey, Philip D.] Bronx VA Med Ctr, VA VISN MIRECC 3, Bronx, NY 10468 USA. [Harvey, Philip D.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RP Bowie, CR (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave,4th Floor,Box 1230, New York, NY 10029 USA. EM christopher.bowie@mssm.edu FU NIMH [MH 63116]; Mt. Sinai Silvio Conte Neuroscience Center [MH 36692]; VA VISN 3 MIRECC FX This research was supported by NIMH Grant Number MH 63116 to Dr. Harvey, the Mt. Sinai Silvio Conte Neuroscience Center (NIMH MH 36692; KL Davis PI) and the VA VISN 3 MIRECC. These sponsors had no role in study design, collection of data, data analysis, interpretation of results, or writing of the manuscript. NR 55 TC 22 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2008 VL 106 IS 1 SI SI BP 50 EP 58 DI 10.1016/j.schres.2007.10.026 PG 9 WC Psychiatry SC Psychiatry GA 377MY UT WOS:000261256500007 PM 18053687 ER PT J AU Stein, PD Gottschalk, A Sostman, HD Chenevert, TL Fowler, SE Goodman, LR Hales, CA Hull, RD Kanal, E Leeper, KV Nadich, DP Sak, DJ Tapson, VF Wakefield, TW Weg, JG Woodard, PK AF Stein, Paul D. Gottschalk, Alexander Sostman, H. Dirk Chenevert, Thomas L. Fowler, Sarah E. Goodman, Lawrence R. Hales, Charles A. Hull, Russell D. Kanal, Emanuel Leeper, Kenneth V., Jr. Nadich, David P. Sak, Daniel J. Tapson, Victor F. Wakefield, Thomas W. Weg, John G. Woodard, Pamela K. TI Methods of Prospective Investigation of Pulmonary Embolism Diagnosis III (ROPED III) SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID MAGNETIC-RESONANCE ANGIOGRAPHY; NEPHROGENIC SYSTEMIC FIBROSIS; VERY-LOW PROBABILITY; MR-ANGIOGRAPHY; CT VENOGRAPHY; VENOUS THROMBOSIS; SERUM CREATININE; CLINICAL-MODEL; LUNG SCANS; PIOPED-II AB In this work, the methods of the Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III) are described in detail. PIOPED III is a multicenter collaborative investigation sponsored by the National Heart, Lung and Blood Institute. The purpose is to determine the accuracy of gadolinium-enhanced magnetic resonance angiography in combination with venous phase magnetic resonance venography for the diagnosis of acute pulmonary embolism (PE). A composite reference standard based on usual diagnostic methods for PE is used. All images will be read by 2 blinded and study-certified central readers. Patients with no PE according to the composite reference test will be randomized to undergo gadolinium-enhanced magnetic resonance angiography in combination with venous phase magnetic resonance venography. This procedure will reduce the proportion of patients with negative tests at no loss in evaluation of sensitivity and specificity. C1 [Stein, Paul D.] St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI USA. [Stein, Paul D.] Wayne State Univ, Dept Med, Detroit, MI 48202 USA. [Gottschalk, Alexander] Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA. [Sostman, H. Dirk] Weill Cornell Med Coll, Off Dean, Houston, TX USA. [Sostman, H. Dirk] Methodist Hosp, Houston, TX 77030 USA. [Chenevert, Thomas L.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Fowler, Sarah E.] George Washington Univ, Ctr Biostat, Dept Epidemiol & Biostat, Rockville, MD USA. [Goodman, Lawrence R.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 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. [Kanal, Emanuel] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Leeper, Kenneth V., Jr.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Nadich, David P.] NYU, Med Ctr, Dept Radiol, New York, NY 10016 USA. [Sak, Daniel J.] St Joseph Mercy Oakland Hosp, Dept Med, Pontiac, MI 48341 USA. [Tapson, Victor F.] Duke Univ, Dept Med, Durham, NC USA. [Wakefield, Thomas W.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Weg, John G.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Woodard, Pamela K.] Washington Univ, Dept Radiol, St Louis, MO USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org FU NHLBI NIH HHS [U01 HL077151, HL177150, U01 HL081593, U01 HL077155, HL077153, HL077155, HL081594, U01 HL077149, U01 HL077358-04, U01 HL081594, HL077154, HL077358, U01 HL077358, HL077151, U01 HL077154, HL081593, HL077149, U01 HL077153] NR 46 TC 22 Z9 25 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD NOV PY 2008 VL 38 IS 6 BP 462 EP 470 DI 10.1053/j.semnuclmed.2008.06.003 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 360IM UT WOS:000260051200008 PM 19331840 ER PT J AU Mikulec, AA Khan, AM Barker, FG McKenna, MJ AF Mikulec, Anthony A. Khan, Aayesha M. Barker, Fred G., II McKenna, Michael J. TI Bilateral Meningoencephalocele Repair Complicated by Superior Semicircular Canal Dehiscence: Case Report SO SKULL BASE-AN INTERDISCIPLINARY APPROACH LA English DT Article DE Meningoencephalocele; tegmental defect; superior semicircular canal dehiscence; hearing loss ID CONDUCTIVE HEARING-LOSS; TEMPORAL BONE; VERTIGO; DEFECTS AB To describe an unusual case of bilateral meningoencephaloceles with concurrent bilateral superior semicircular canal dehiscene (SSCD) and to discuss the clinical presentation, diagnosis, and treatment of SSCD. A 34-year-old man presented with unsteadiness and bilateral conductive hearing loss. He was diagnosed with bilateral meningoencephaloceles and underwent staged middle fossa approaches for repair. Following the second (right-sided) surgery, he developed sensorineural hearing loss and severe dizziness, indicating labyrinthine insult in the operated ear. He was then referred to our institution for further management. On our evaluation, the patient was continuing to experience disequilibrium and sensitivity to loud sounds. Examination revealed a positive Hennebert's sign and nystagmus consistent with symptomatic SSCD in the left ear. Computed tomography scanning with reformatting into Poeschel and Stenvers views identified bilateral SSCD. Plugging of the left SSCD was performed via a middle cranial fossa approach and resulted in improvement of the conductive hearing loss and after a period of compensation, resolution of the vestibular symptoms. This case illustrates that tegmental defects may result in simultaneous meningoencepaholcele and SSCD that may complicate their repair. The importance of having a high index of suspicion and evaluation with high resolution CT scanning with appropriate reformatting is emphasized. When present and symptomatic, SSCD can be successfully managed by plugging the canal. C1 [Mikulec, Anthony A.; Khan, Aayesha M.] St Louis Univ, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63103 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Mikulec, AA (reprint author), Washington Univ, Sch Med, Dept Otolaryngol, 3660 Vista Ave,Suite 312, St Louis, MO 63110 USA. EM ANTHONY.Mikulec@tenethealth.com NR 14 TC 6 Z9 6 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1531-5010 J9 SKULL BASE-INTERD AP JI Skull Base-Interdiscip. Appr. PD NOV PY 2008 VL 18 IS 6 BP 423 EP 428 DI 10.1055/s-0028-1087217 PG 6 WC Clinical Neurology; Otorhinolaryngology; Surgery SC Neurosciences & Neurology; Otorhinolaryngology; Surgery GA 378YL UT WOS:000261361000010 PM 19412414 ER PT J AU Sobo, EJ Bowman, C Gifford, AL AF Sobo, Elisa J. Bowman, Candice Gifford, Allen L. TI Behind the scenes in health care improvement: The complex structures and emergent strategies of Implementation Science SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; Implementation science; Structure and agency; Health Services Research; Social construction of knowledge; Institutional ethnography ID CLINICAL REMINDERS; BARRIERS; MEDICINE AB Implementation Science (IS) is a new branch of health services research (HSR) that strives to increase the efficiency and effectiveness of health care quality improvement (QI) efforts. Despite the fact that IS takes a systems approach, building contextual factors into its research designs, the complex systems context of IS itself-and the impact this context has on IS practice-has never been scrutinized. Using individual interviews and participant observation, the research described here characterizes key contextual factors affecting how implementation scientists in one large health care organization approach and conduct their research. Some of the organizational and professional system forces structuring their attitudes and actions were grant-related timelines, administrative burdens, and team turnover. The need for publications also figured highly. While such pressures (and related responses to them) may be rife in most grant-funded health care research settings, IS's particularly marginal position drove these implementation scientists to strategically highlight particular aspects of their work depending on which audience or part of the system they required favor from. Their narratives illuminate the contradictions and contests entailed within and engendered by organizational and professional structures, and the strategies used to negotiate these. They also reveal a great deal about the struggles underwriting disciplinary identity claims in a complex systems context. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Sobo, Elisa J.] San Diego State Univ, Dept Anthropol, San Diego, CA 92182 USA. [Bowman, Candice] Greater Los Angeles VA Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. [Gifford, Allen L.] Boston Univ, Boston, MA 02215 USA. [Gifford, Allen L.] VA New England Healthcare Syst, Ctr Healthcare Qual Outcomes & Econ Res, Bedford, MA USA. RP Sobo, EJ (reprint author), San Diego State Univ, Dept Anthropol, San Diego, CA 92182 USA. EM esobo@mail.sdsu.edu; candybowman@gmail.com; allen.gifford@va.gov NR 33 TC 17 Z9 17 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 2008 VL 67 IS 10 BP 1530 EP 1540 DI 10.1016/j.socscimed.2008.06.001 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 370HU UT WOS:000260754100007 PM 18760519 ER PT J AU Schaefer, PW Barak, ER Kamalian, S Gharai, LR Schwamm, L Gonzalez, RG Lev, MH AF Schaefer, Pamela W. Barak, Elizabeth R. Kamalian, Shahmir Gharai, Leila Rezai Schwamm, Lee Gonzalez, Ramon Gilberto Lev, Michael H. TI Quantitative Assessment of Core/Penumbra Mismatch in Acute Stroke CT and MR Perfusion Imaging Are Strongly Correlated When Sufficient Brain Volume Is Imaged SO STROKE LA English DT Article DE acute ischemic; acute stroke; CT; MRI; penumbra; perfusion CT imaging; perfusion MR imaging ID HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; BLOOD-FLOW; TIME WINDOW; THROMBOLYSIS; PENUMBRA; DESMOTEPLASE; DIFFUSION; INFARCT; ECASS AB Background and Purpose-Our purpose was to determine (1) the correlation between quantitative CT and MR measurements of infarct core, penumbra, and mismatch; and (2) whether the difference between these measurements would alter patient selection for stroke clinical trials. Methods-We studied 45 patients with acute middle cerebral artery stroke imaged a mean of 3.8 hours after onset (range, 0.48 to 8.35 hours) who underwent CT perfusion and MR diffusion (DWI)/perfusion imaging within 3 hours of each other. The DWI and MR-mean transit time (MTT) abnormalities were visually segmented using a semiautomated commercial analysis program. The CT-cerebral blood volume) and CT-MTT lesions were automatically segmented using a relative cerebral blood volume threshold of 0.56 and a relative MTT threshold of 1.50 on commercially available software. Percent mismatch was defined as [(MTT-DWI)/DWI volume] x 100. Pearson correlation coefficients were calculated. Results-There were significant correlations for DWI versus CT-cerebral blood volume lesion volumes (r(2) = 0.88, P < 0.001), for MR-MTT versus CT-MTT lesion volumes(r(2) = 0.86, P < 0.001), and for MR-MTT/DWI versus CT-MTT/CT-cerebral blood volume mismatch lesion volumes(r(2) = 0.81, P < 0.001). MR perfusion and CT perfusion agreed for determining: (1) infarct core < versus >= 100 mL in 41 of 45 (91.1%); (2) MTT lesion size < versus > 2 cm diameter in 42 of 45 (93.3%); (3) mismatch < versus > 20% in 41 of 45 (91.1%); and (4) inclusion versus exclusion from trial enrollment in 38 of 45 (84.4%) patients. Six of 7 disagreements were due to inadequate CT coverage. Conclusion-Advanced MR and CT perfusion imaging measurements of core/penumbra mismatch for patient selection in stroke trials are highly correlated when CT perfusion coverage is sufficient to include most of the ischemic region. Although MR is currently the preferred imaging method for determining core and penumbra, CT perfusion is comparable and potentially more available. (Stroke. 2008; 39: 2986-2992.) C1 [Schaefer, Pamela W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. [Schwamm, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Neuroradiol, Gray 273A,55 Fruit St, Boston, MA 02114 USA. EM pschaefer@partners.org OI Kamalian, Shahmir/0000-0002-9640-8144; Schwamm, Lee/0000-0003-0592-9145 NR 18 TC 94 Z9 100 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2008 VL 39 IS 11 BP 2986 EP 2992 DI 10.1161/STROKEAHA.107.513358 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 365SC UT WOS:000260427100013 PM 18723425 ER PT J AU Greer, DM Funk, SE Reaven, NL Ouzounelli, M Uman, GC AF Greer, David M. Funk, Susan E. Reaven, Nancy L. Ouzounelli, Myrsini Uman, Gwen C. TI Impact of Fever on Outcome in Patients With Stroke and Neurologic Injury A Comprehensive Meta-Analysis SO STROKE LA English DT Article DE fever; meta-analysis; outcome; stroke; traumatic brain injury ID INTENSIVE-CARE-UNIT; ADMISSION BODY-TEMPERATURE; INTRACEREBRAL HEMORRHAGE; SUBARACHNOID HEMORRHAGE; HYPERTHERMIA; MORTALITY; PYREXIA; SEVERITY; ISCHEMIA AB Background and Purpose-Many studies associate fever with poor outcome in patients with neurological injury, but this relationship is blurred by divergence in populations and outcome measures. We sought to incorporate all recent scholarship addressing fever in brain-injured patients into a comprehensive meta-analysis to evaluate disparate clinical findings. Methods-We conducted a Medline search for articles since January 1, 1995 (in English with abstracts, in humans) and hand searches of references in bibliographies and review articles. Search terms covered stroke, neurological injury, thermoregulation, fever, and cooling. A total of 1139 citations were identified; we retained 39 studies with 67 tested hypotheses contrasting outcomes of fever/higher body temperature and normothermia/lower body temperature in patients with neurological injury covering 14 431 subjects. A separate meta-analysis was performed for each of 7 outcome measures. Significance was evaluated with Zc developed from probability values or t values. Correlational effect size, r((es)), was calculated for each study and used to derive Cohen's d unbiased combined effect size and relative risk. Results-Fever or higher body temperature was significantly associated with worse outcome in every measure studied. Relative risk of worse outcome with fever was: mortality, 1.5; Glasgow Outcome Scale, 1.3; Barthel Index, 1.9; modified Rankin Scale, 2.2; Canadian Stroke Scale, 1.4; intensive care length of stay, 2.8; and hospital length of stay, 3.2. Conclusions-In the pooled analyses covering 14 431 patients with stroke and other brain injuries, fever is consistently associated with worse outcomes across multiple outcome measures. (Stroke. 2008; 39: 3029-3035.) C1 [Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Funk, Susan E.; Reaven, Nancy L.; Ouzounelli, Myrsini] Strateg Hlth Resources, La Canada Flintridge, CA USA. [Uman, Gwen C.] Vital Res LLC, Los Angeles, CA USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 835,55 Fruit St, Boston, MA 02114 USA. EM Zgreer@partners.org FU Medivance, Inc FX S.E.F., N.L.R., M.O., and G.C.U. report financial support from Medivance, Inc under an agreement that the study be conducted independently to reduce funding bias. Accordingly, the study was designed, conducted, analyzed, interpreted, and written by investigators independent of Medivance and was not sent to agents of Medivance for prepublication review or approval. NR 23 TC 131 Z9 135 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2008 VL 39 IS 11 BP 3029 EP 3035 DI 10.1161/STROKEAHA.108.521583 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 365SC UT WOS:000260427100020 PM 18723420 ER PT J AU Yin, W Signore, AP Iwai, M Cao, GD Gao, YQ Chen, J AF Yin, Wei Signore, Armando P. Iwai, Masanori Cao, Guodong Gao, Yanqin Chen, Jun TI Rapidly Increased Neuronal Mitochondrial Biogenesis After Hypoxic-Ischemic Brain Injury SO STROKE LA English DT Article DE neonatal hypoxic ischemia; mitochondria biogenesis; nuclear respiratory factor-1; mitochondrial transcription factor A ID RESPIRATORY FACTOR-I; RAT; PROTEIN; NEURODEGENERATION; INDUCTION; DEATH; CELLS; GAMMA AB Background and Purpose-Mitochondrial biogenesis is regulated through the coordinated actions of both nuclear and mitochondrial genomes to ensure that the organelles are replenished on a regular basis. This highly regulated process has been well defined in skeletal and heart muscle, but its role in neuronal cells, particularly when under stress or injury, is not well understood. In this study, we report for the first time rapidly increased mitochondrial biogenesis in a rat model of neonatal hypoxic/ischemic brain injury (H-I). Methods-Postnatal day 7 rats were subjected to H-I induced by unilateral carotid artery ligation followed by 2.5 hours of hypoxia. The relative amount of brain mitochondrial DNA (mtDNA) was measured semiquantitatively using long fragment PCR at various time points after H-I. HSP60 and COXIV proteins were detected by Western blot. Expression of three genes critical for the transcriptional regulation of mitochondrial biogenesis, peroxisome proliferator-activated receptor coactivator-1 (PGC-1), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM), were examined by Western blot and RT-PCR. Results-Brain mtDNA content was markedly increased 6 hours after H-I, and continued to increase up to 24 hours after H-I. Paralleling the temporal change in mtDNA content, mitochondrial number and proteins HSP60 and COXIV, and citrate synthase activity were increased in neurons in the cortical infarct border zone after H-I. Moreover, cortical expression of NRF-1 and TFAM were increased 6 to 24 hours after H-I, whereas PGC-1 was not changed. Conclusions-Neonatal H-I brain injury rapidly induces mitochondrial biogenesis, which may constitute a novel component of the endogenous repair mechanisms of the brain. (Stroke. 2008; 39: 3057-3063.) C1 [Yin, Wei; Signore, Armando P.; Iwai, Masanori; Cao, Guodong; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Cao, Guodong; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Cao, Guodong; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Signore, Armando P.; Cao, Guodong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507 Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU NIH/NINDS [NS45048, NS36736, NS43802, NS44178]; Geriatric Research, Education and Clinical Center; Veterans Affairs; Pittsburgh Health Care System, Pittsburgh, Pennsylvania FX This project was supported by NIH/NINDS grants NS45048, NS36736, NS43802, and NS44178. J.C. was also supported in part by the Geriatric Research, Education and Clinical Center, Veterans Affairs, Pittsburgh Health Care System, Pittsburgh, Pennsylvania. NR 30 TC 110 Z9 122 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2008 VL 39 IS 11 BP 3057 EP 3063 DI 10.1161/STROKEAHA.108.520114 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 365SC UT WOS:000260427100024 PM 18723421 ER PT J AU Schaefer, PW Yoo, AJ Bell, D Barak, ER Romero, JM Nogueira, RG Lev, MH Schwamm, LH Gonzalez, RG Hirsch, JA AF Schaefer, Pamela W. Yoo, Albert J. Bell, Donnie Barak, Elizabeth R. Romero, Javier M. Nogueira, Raul G. Lev, Michael H. Schwamm, Lee H. Gonzalez, Ramon G. Hirsch, Joshua A. TI CT Angiography-Source Image Hypoattenuation Predicts Clinical Outcome in Posterior Circulation Strokes Treated With Intra-Arterial Therapy SO STROKE LA English DT Article DE acute stroke; CT; ischemia; neuroradiology; perfusion; stroke; therapy ID BASILAR ARTERY-OCCLUSION; PERFUSION COMPUTED-TOMOGRAPHY; MIDDLE CEREBRAL-ARTERY; THROMBOLYSIS; RECANALIZATION AB Background and Purpose-The aim of this study was to correlate CT angiography-source image (CTA-SI) parenchymal hypoattenuation with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis. Methods-In 16 patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis, we graded CTA-SI parenchymal hypoattenuation in the medulla, pons, midbrain, thalamus, cerebellum, occipital lobe, inferior parietal lobe, and medial temporal lobe. The grading scale was: 0, no hypoattenuation; 1, < 50% hypoattenuation; and 2, > 50% hypoattenuation. On CTA, we assessed clot location and length and collaterals. Outcome was measured with modified Rankin score. Results-Mean patient age was 68.3 years (range, 47 to 86 years), National Institutes of Health Stroke Scale was 28 (range, 11 to 40), time to CTA was 5.2 hours (range, 0.69 to 15.32), and time from CTA to intra-arterial thrombolysis was 5 hours (range, 2.25 to 10.38 hours). There were 4 basilar, 2 vertebral, and 10 combined occlusions. Eleven patients had near complete, 4 had partial, and one had no recanalization. Independent outcome predictors measured as modified Rankin score at 3 months were CTA-SI pons and midbrain scores(cumulative r = 0.81, P < 0.001). For outcome dichotomized into death versus survival, the CTA-SI pons score (P = 0.0037) was the only independent predictor. Conclusion-Hypoattenuation in the pons and midbrain on pretreatment CTA-SI correlates highly with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis. (Stroke. 2008;39:3107-3109.) C1 [Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Neuroradiol, Boston, MA 02114 USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Neuroradiol, Gray 375,55 Fruit St, Boston, MA 02114 USA. EM pschaefer@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 10 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2008 VL 39 IS 11 BP 3107 EP 3109 DI 10.1161/STROKEAHA.108.517680 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 365SC UT WOS:000260427100035 PM 18703807 ER PT J AU Demirjian, AN Grossman, JM Chan, JL Parangi, S AF Demirjian, Aram N. Grossman, Joseph M. Chan, Jean L. Parangi, Sareh TI Parathyroid carcinoma and neurofibromatosis SO SURGERY LA English DT Article ID MULTIPLE-ENDOCRINE-NEOPLASIA; PRIMARY HYPERPARATHYROIDISM C1 [Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02214 USA. [Demirjian, Aram N.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Grossman, Joseph M.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Chan, Jean L.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Parangi, S (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC460, Boston, MA 02214 USA. EM sparangi@partners.org NR 11 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2008 VL 144 IS 5 BP 827 EP 829 DI 10.1016/j.surg.2008.07.015 PG 3 WC Surgery SC Surgery GA 372NK UT WOS:000260908100016 PM 19081027 ER PT J AU Donze, J Le Gal, G Fine, MJ Roy, PM Sanchez, O Verschuren, F Cornuz, J Meyer, G Perrier, A Righini, M Aujesky, D AF Donze, Jacques Le Gal, Gregoire Fine, Michael J. Roy, Pierre-Marie Sanchez, Olivier Verschuren, Franck Cornuz, Jacques Meyer, Guy Perrier, Arnaud Righini, Marc Aujesky, Drahomir TI Prospective validation of the Pulmonary Embolism Severity Index A clinical prognostic model for pulmonary embolism SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Pulmonary embolism; prediction rule; prognosis; risk; validation study ID MOLECULAR-WEIGHT HEPARIN; LOW-RISK PATIENTS; DEEP-VEIN THROMBOSIS; OUTPATIENT TREATMENT; VENOUS THROMBOEMBOLISM; COMPUTED-TOMOGRAPHY; PREDICTION RULE; MANAGEMENT; ULTRASONOGRAPHY; TRIAL AB Practice guidelines recommend outpatient care for selected patients with non-massive pulmonary embolism (PE), but fail to specify how these low-risk patients should be identified. Using data from U.S. patients, we previously derived the Pulmonary Embolism Severity Index (PESI), a prediction rule that risk stratifies patients with PE. We sought to validate the PESI in a European patient cohort. We prospectively validated the PESI in patients with PE diagnosed at six emergency departments in three European countries. We used baseline data for the rule's II prognostic variables to stratify patients into five risk classes (I-V) of increasing probability of mortality. The outcome was overall mortality at 90 days after presentation. To assess the accuracy of the PESI to predict mortality, we estimated the sensitivity, specificity, and predictive values for low- (risk classes I/II) versus higher-risk patients (risk classes III-V), and the discriminatory power using the area under the receiver operating characteristic (ROC) curve. Among 357 patients with PE, overall mortality was 5.9%, ranging from 0% in class I to 17.9% in class V. The 186 (52%) low-risk patients had an overall mortality of 1.1% (95% confidence interval [CI]: 0.1-3.8%) compared to 11.1% (95% CI: 6.8-16.8%) in the 171 (48%) higher-risk patients. The PESI had a high sensitivity (91%, 95% CI: 71-97%) and a negative predictive value (99%,95% CI: 96-100%) for predicting mortality. The area under the ROC curve was 0.78 (95% 0: 0.70-0.86). The PESI reliably identifies patients with PE who are at low risk of death and who are potential candidates for outpatient care. The PESI may help physicians make more rational decisions about hospitalization for patients with PE. C1 [Donze, Jacques; Cornuz, Jacques; Aujesky, Drahomir] Univ Lausanne, Div Gen Internal Med, Lausanne, Switzerland. [Le Gal, Gregoire] Univ Brest, Dept Internal Med & Chest Dis, Brest, France. [Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Roy, Pierre-Marie] Univ Angers, Dept Emergency Med, Angers, France. [Sanchez, Olivier; Meyer, Guy] Hop Europeen Georges Pompidou, Dept Resp & Crit Care Med, Paris, France. [Verschuren, Franck] St Luc Univ Hosp, Dept Emergency, Brussels, Belgium. [Perrier, Arnaud] Univ Geneva, Div Gen Internal Med, Geneva, Switzerland. [Righini, Marc] Univ Geneva, Div Angiol & Hemostasis, Geneva, Switzerland. RP Donze, J (reprint author), CHU Vaudois, Serv Med Interne, CH-1011 Lausanne, Switzerland. EM jacques.donze@chuv.ch RI LE GAL, Gregoire/K-1077-2012; Perrier, Arnaud/M-2263-2014; OI LE GAL, Gregoire/0000-0002-9253-248X NR 32 TC 100 Z9 103 U1 1 U2 6 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD NOV PY 2008 VL 100 IS 5 BP 943 EP 948 DI 10.1160/TH08-05-0285 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 373GE UT WOS:000260958200036 PM 18989542 ER PT J AU Yin, XM Latif, R Bahn, R Tomer, Y Davies, TF AF Yin, Xiaoming Latif, Rauf Bahn, Rebecca Tomer, Yaron Davies, Terry F. TI Influence of the TSH Receptor Gene on Susceptibility to Graves' Disease and Graves' Ophthalmopathy SO THYROID LA English DT Article ID AUTOIMMUNE THYROID-DISEASE; HUMAN THYROTROPIN RECEPTOR; MOLECULAR-CLONING; ASSOCIATION; POLYMORPHISM; DOMAIN; CTLA-4; LOCI; DISCOVERY; CD28 AB Background: A large gene region, called GD-1, was first described by this laboratory as linked to Graves' disease (GD) and included the gene for the thyroid-stimulating hormone receptor (TSHR). Recent studies have now suggested an association of TSHR intronic polymorphisms with GD. We have taken the opportunity to examine a population of well-characterized patients with autoimmune thyroid disease (AITD) typed for an additional thyroid susceptibility gene, the immunoregulatory gene for cytotoxic T-lymphocyte antigen 4 (CTLA-4), to examine its relationship with the susceptibility to GD endowed by TSHR gene polymorphisms. Methods: We used TSHR-SNP-rs2268458, located in intron 1 of the TSHR gene, measured using standard PCR-RFLP procedures, as our marker for the TSHR gene association. We genotyped 200 patients with GD, 83 patients with Hashimoto's thyroiditis (HT), and 118 healthy controls (all female Caucasians). Results: The allele and genotype frequencies from GD patients, but not HT patients, were significantly different from controls. The frequency of the combined genotype (allele) CC + TC was significantly higher in GD patients versus controls, suggesting that the C-containing genotype increased the risk for GD in a dominant manner (p = 0.018, odds ratio [OR] = 1.8). When compared with CTLA-4 (A/G)(49) single-nucleotide polymorphism (SNP), we were unable to demonstrate additive risk in patients with established AITD. Further, subsetting the patients (n = 120) into those with clinically significant Graves' ophthalmopathy (GO) showed no association with the TSHR SNP. Conclusions: These results demonstrated that the intronic TSHR-SNP-rs2268458 was associated with GD, but not with HT, thus indicating that the TSHR gene has the potential to increase susceptibility to GD. However, we were not able to demonstrate any additive risk with the CTLA-4 (A/G)(49) SNP, which is, therefore, an independent risk factor for AITD. This suggested that, within the limits of the study population, each of these two genes provided a small contribution to GD susceptibility and that neither was essential. In addition, there was no evidence for the TSHR gene association adding to the risk of developing GO. Direct functional analyses are now needed to help explain the mechanisms of this TSHR gene susceptibility to GD. C1 [Yin, Xiaoming; Latif, Rauf; Davies, Terry F.] Mt Sinai Med Ctr, James J Peters VA Med Ctr, Thyroid Res Unit, New York, NY 10029 USA. [Bahn, Rebecca] Mayo Clin, Div Endocrinol, Rochester, MN USA. [Tomer, Yaron] Univ Cincinnati, Div Endocrinol, Cincinnati, OH USA. RP Davies, TF (reprint author), Mt Sinai Med Ctr, James J Peters VA Med Ctr, Thyroid Res Unit, Box 1055 1 Gustave L Levy Pl, New York, NY 10029 USA. EM terry.davies@mssm.edu FU NIH-NIDDKD [DK052464, DK69713] FX This work was supported in part by DK052464 and DK69713 from NIH-NIDDKD, the David Owen Segal Endowment, the James J. Peters VAMC, and the VA Merit Award program. NR 38 TC 28 Z9 31 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2008 VL 18 IS 11 BP 1201 EP 1206 DI 10.1089/thy.2008.0098 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 373GG UT WOS:000260958400009 PM 18925838 ER PT J AU McCutcheon, SR AF McCutcheon, Stephen R. TI Addressing Problems of Insufficient Competence During the Internship Year SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE predoctoral internship; insufficient competence; competencies; due process; remediation AB Addressing problems of insufficient student competence during the internship year takes on special importance at this penultimate step in the trainee's entry to the profession. The gravity of gate-keeping functions at this late stage of training requires internship faculties to accurately identify the trainees lacking sufficient competence, and to be mindful of errors resulting from assessments of competence that lack adequate sensitivity and specificity. This process occurs within larger systemic and legal contexts described in companion articles contained in this issue. This article serves as an extension of the issues raised in this special section as they apply to the internship year. C1 [McCutcheon, Stephen R.] Puget Sound Healthcare Syst, Vet Affairs, Seattle, WA USA. RP McCutcheon, SR (reprint author), VA Puget Sound, Mental Hlth 116, 1660 South Columbian Way, Seattle, WA 98108 USA. EM stephen.mccutcheon@va.gov NR 15 TC 7 Z9 7 U1 1 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD NOV PY 2008 VL 2 IS 4 BP 210 EP 214 DI 10.1037/a0013535 PG 5 WC Psychology, Educational SC Psychology GA V29EE UT WOS:000208730900004 ER PT J AU Dasgupta, SK Abdel-Monem, H Guchhait, P Nagata, S Thiagarajan, P AF Dasgupta, Swapan K. Abdel-Monem, Hanan Guchhait, Prasenjit Nagata, Shigekazu Thiagarajan, Perumal TI Role of lactadherin in the clearance of phosphatidylserine-expressing red blood cells SO TRANSFUSION LA English DT Article ID MEMBRANE PHOSPHOLIPID ASYMMETRY; APOPTOTIC CELLS; HUMAN-ERYTHROCYTES; PROLONGED STORAGE; PHAGOCYTOSIS; MACROPHAGES; ENGULFMENT; EXPOSURE; BINDING; ADHESION AB In red blood cells (RBCs) anionic phospholipids, such as phosphatidylserine, are present in the inner leaflet of the membrane bilayer. Exposure of phosphatidylserine occurs during senescence and during long-term storage of RBCs and is considered as the tag for removal from the circulation by macrophages. Lactadherin is a phosphatidylserine-binding glycoprotein secreted by macrophages that promotes the engulfment of phosphatidylserine-expressing apoptotic lymphocytes. This study investigates the role of lactadherin in the phagocytosis of phosphatidylserine-expressing RBCs. Transbilayer movement of phosphatidylserine was induced in RBCs either by storage beyond 30 days or by treatment with calcium ionophore A23187 and N-ethylmaleimide. Phosphatidylserine-expressing RBCs were incubated with phorbol ester-stimulated THP-1, and phagocytosis was determined by measuring the pseudoperoxidase activity of hemoglobin. The in vivo clearance of phosphatidylserine-enriched RBCs was measured in lactadherin-deficient mice and in their littermate controls. Lactadherin promoted phagocytosis of phosphatidylserine-expressing RBCs by macrophages in a concentration-dependent manner. Splenic macrophages from lactadherin-deficient mice had diminished capacity to phagocytose phosphatidylserine-expressing RBCs. The life span of RBCs in lactadherin-deficient mice was similar to wild-type littermate controls in vivo. However, when an excess of phosphatidylserine-expressing RBCs were infused, there was only a mild impairment in the clearance in lactadherin-deficient mice compared to wild-type littermate controls. These results show that clearance of phosphatidylserine-expressing RBCs is not diminished in a significant way in lactadherin-deficient mice under physiologic conditions and suggest the presence of redundant pathways. C1 [Thiagarajan, Perumal] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Osaka Univ, Sch Med, Dept Genet, Osaka, Japan. RP Thiagarajan, P (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Mail Stop 113,2002 Holcombe Blvd, Houston, TX 77030 USA. EM perumalt@bcm.tmc.edu OI Thiagarajan, Perumal/0000-0003-2186-7036 FU Veterans Affairs Research Service and the Gulf Coast Blood Center; American Heart Association FX Supported by grants from the Veterans Affairs Research Service and the Gulf Coast Blood Center (PT) and a Grant in Aid from American Heart Association (PG). NR 39 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2008 VL 48 IS 11 BP 2370 EP 2376 DI 10.1111/j.1537-2995.2008.01841.x PG 7 WC Hematology SC Hematology GA 375AZ UT WOS:000261086200017 PM 18647368 ER PT J AU Staropoli, JF Van Cott, EM Makar, RS AF Staropoli, John F. Van Cott, Elizabeth M. Makar, Robert S. TI Membrane autoantibodies in systemic lupus erythematosus: a case of autoimmune hemolytic anemia, antiphospholipid antibodies, and transient acquired activated protein C resistance SO TRANSFUSION LA English DT Article ID IGM AUTOAGGLUTININS; CLINICAL-SIGNIFICANCE; WARM AUTOANTIBODIES; COLD; ANTICOAGULANTS; CELLS AB Warm autoimmune hemolytic anemia and antiphospholipid antibodies (which include lupus anticoagulants and anticardiolipin [ACL] antibodies) are associated, respectively, with approximately 10 and 40 percent of cases of systemic lupus erythematosus (SLE). This study reports a case of SLE presenting with an unusual constellation of findings that included an immunoglobulin M (IgM) cold autoantibody of high thermal amplitude, high-titer ACL antibodies, and transient acquir ed activated protein C resistance. A previously untransfused, nulligravid 17-year-old woman without a significant medical history presented with signs and symptoms of SLE and an extravascular hemolytic anemia. Spontaneous agglutination was noted in blood samples collected for testing. Serologic testing revealed a normal-titer, high-thermal-amplitude IgM red blood cell (RBC) autoantibody but no additional RBC antibodies in the patient's plasma. Additional testing was significant for a high-titer ACL IgM and a positive test for activated protein C resistance (a screening test for the Factor [F]V Leiden mutation), which prompted initiation of prophylactic anticoagulation. Confirmatory DNA testing for FV Leiden, however, was negative. The patient's symptoms, anemia, RBC autoagglutinins, ACL antibodies, and activated protein C resistance all resolved after 6 weeks of immunosuppression. This case illustrates the wide range of clinical and laboratory findings that autoantibodies against cellular membranes may produce. IgM autoagglutinins of high thermal amplitude associated with a significant extravascular hemolytic anemia may be a presenting feature of SLE. Concomitant antiphospholipid antibodies may interfere with partial thromboplastin time-based tests of hypercoagulability such as that for activated protein C resistance. C1 [Staropoli, John F.; Van Cott, Elizabeth M.; Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, 55 Fruit St,GRJ-2-206C, Boston, MA 02114 USA. EM rmakar@partners.org NR 38 TC 2 Z9 2 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2008 VL 48 IS 11 BP 2435 EP 2441 DI 10.1111/j.1537-2995.2008.01877.x PG 7 WC Hematology SC Hematology GA 375AZ UT WOS:000261086200026 PM 18673345 ER PT J AU Sun, HY Singh, N Cacciarelli, TV Wannstedt, C Wagener, MM Steele, C AF Sun, Hsin-Yun Singh, Nina Cacciarelli, Thomas V. Wannstedt, Cheryl Wagener, Marilyn M. Steele, Chad TI Dysregulated expression of T-helper cell responses and susceptibility to infections in high-risk liver transplant recipients SO TRANSPLANT IMMUNOLOGY LA English DT Article DE Transplants; Cytomegalovirus; Fungal infections; Bacterial infections; T-helper cells; Cytokines ID RENAL REPLACEMENT THERAPY; CYTOMEGALOVIRUS-INFECTION; MONONUCLEAR PHAGOCYTES; HEMODIALYSIS-PATIENTS; ANTIFUNGAL ACTIVITY; PREEMPTIVE THERAPY; CYTOKINE; DIALYSIS; MORTALITY; PROFILES AB Background: Liver transplant recipients requiring dialysis have poor outcomes including higher risk of infection, and allograft rejection. The role of T-helper cell cytokine responses in the pathogenesis of infections in these patients has not been fully defined. Methods: Cases were 11 dialyzed liver transplant recipients. Controls (2 for each case) were patients who were transplanted next to the case but did not require dialysis at any time before or after transplantation. Cytokine responses were assessed in sera collected immediately before transplantation. Data were analyzed for candidate cytokines for pro-inflammatory Th1 (IL-1 beta, IL-12p70, and IFN-gamma), and Th17 (IL-12p40, IL-17), and anti-inflammatory Th2 phenotypes (IL-4, IL-5, IL-10, and IL-13). Results: Cases were more likely to have an increase in any of the Th1 or Th1 and Th17 cytokines than the controls (p = 0.016 and p = 0.04, respectively). Major infections developed in 27% of the study population: these included 46% of the cases and 18%, of the controls (p = 0.09). Patients with infections vs. those without these were more likely to have an increase in any of the Th2 cytokines (p = 0.005). CMV viremia occurred in 30% of the patients and was significantly associated with Th1 responses even when adjusted for CMV recipient/donor serostatus or any major infection (OR 3.2. 95% CI 0.96-10.73, p = 0.05). Conclusions: Requirement of dialysis was characterized by a state of heightened expression of inflammatory responses. However, patients developing infections preferentially expressed Th2 phenotype that may act as a negative regulator of protective inflammatory responses. An enhanced expression of inflammatory mediators may serve to promote CMV infection in liver transplant recipients. (C) 2008 Elsevier B.V. All rights reserved. C1 [Singh, Nina; Cacciarelli, Thomas V.; Wannstedt, Cheryl; Wagener, Marilyn M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei, Taiwan. [Steele, Chad] Univ Alabama, Birmingham, AL USA. RP Singh, N (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM nis5@pitt.edu; chadsteele@uab.edu OI SUN, HSIN-YUN/0000-0003-0074-7721 NR 46 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD NOV PY 2008 VL 20 IS 1-2 BP 68 EP 72 DI 10.1016/j.trim.2008.08.001 PG 5 WC Immunology; Transplantation SC Immunology; Transplantation GA 385TX UT WOS:000261837600013 PM 18761089 ER PT J AU Oku, M Okumi, M Sahara, H Hirakata, A Onoe, T Griesemer, AD Yamada, K AF Oku, Manei Okumi, Masayoshi Sahara, Hisashi Hirakata, Atsushi Onoe, Takashi Griesemer, Adam D. Yamada, Kazuhiko TI Porcine CFSE mixed lymphocyte reaction and PKH-26 cell-mediated lympholysis assays SO TRANSPLANT IMMUNOLOGY LA English DT Article DE CFSE; PKH-26; MHC-inbred swine; Radiation-free CML/MLR ID MAJOR HISTOCOMPATIBILITY COMPLEX; SLA CLASS-I; MINIATURE SWINE; T-CELLS; RENAL-ALLOGRAFTS; TRANSPLANTATION TOLERANCE; INDUCTION; VITRO; 2-HAPLOTYPE; SPECIFICITY AB Mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) are widely used to assess T cell responses. A major limitation of the traditional MLR and CIVIL assays is that they require radioisotope labeling with (3)H for MLR and (51)Cr for CML, thereby limiting their use to laboratories with the capabilities to deal safely with these materials. Recently, flow cytometry with CFSE labeling has been used to detect cell division in rodent and human assays, and flow cytometry with PKH-26 labeling has been used to study cytotoxicity in murine models. Partially inbred miniature swine provide a unique large animal preclinical model for experimental transplantation, helping to bridge the gap between rodent and clinical studies. In this study, we modified the reported CFSE and PKH-26 labeling procedures for use with porcine cells, and established that these radioactive-free MLR and CIVIL assays are comparable to traditional radioactive CML and MLR assays for assessing immunologic responses in miniature swine. To our knowledge, this is the first report that has directly compared the traditional CML/MLR with radiation-free CML/MLR in MHC-defined swine models. Objective: The aim of this study is to establish non-radiolabeled CSFE and PKH-26 labeling procedures for flow cytometry based CML/MLR assays that are comparable to radioactive CML/MLR assays in preclinical large animals. (C) 2008 Elsevier B.V. All rights reserved. C1 [Oku, Manei; Okumi, Masayoshi; Sahara, Hisashi; Yamada, Kazuhiko] Kagoshima Univ, Frontier Sci Res Ctr, Kagoshima 8908520, Japan. [Hirakata, Atsushi; Onoe, Takashi; Griesemer, Adam D.; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Yamada, K (reprint author), Kagoshima Univ, Frontier Sci Res Ctr, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan. EM kyyamada@m2.kufm.kagoshima-u.ac.jp FU Japanese Society for the Promotion of Science [A-19209043, B-19390422] FX This study is supported by the Japanese Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A-19209043 and B-19390422). We thank Dr. Isabel McMorrow for critical review of this manuscript. We would also like to thank Emma Samelson-Jones for editorial assistance. NR 29 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD NOV PY 2008 VL 20 IS 1-2 BP 78 EP 82 DI 10.1016/j.trim.2008.07.006 PG 5 WC Immunology; Transplantation SC Immunology; Transplantation GA 385TX UT WOS:000261837600015 PM 18718865 ER PT J AU del Rio, ML Buhler, L Gibbons, C Tian, J Rodriguez-Barbosa, JI AF del Rio, Maria-Luisa Buhler, Leo Gibbons, Carrie Tian, Jiong Rodriguez-Barbosa, Jose-Ignacio TI PD-1/PD-L1, PD-1/PD-L2, and other co-inhibitory signaling pathways in transplantation SO TRANSPLANT INTERNATIONAL LA English DT Review DE antigen-presenting cells; BTLA; CD160; co-inhibition; co-stimulation; HVEM; PD-1; PD-L1; PD-L2; peripheral tolerance; T cells; transplantation ID T-CELL-ACTIVATION; HERPESVIRUS ENTRY MEDIATOR; B7 FAMILY-MEMBER; MISMATCHED CARDIAC ALLOGRAFTS; RESPONSES IN-VIVO; LYMPHOCYTE ATTENUATOR; ORGAN-TRANSPLANTATION; ALLOIMMUNE RESPONSES; PROGRAMMED DEATH-1; CTLA-4-MEDIATED INHIBITION AB Transplantation of cells, tissues and vascularized solid organs is a successful therapeutic intervention for many end-stage chronic diseases. The combination of co-stimulatory blockade with the delivery of negative signals to T cells through co-inhibitory receptors would provide a robust approach to modulating T-cell receptor signaling and improving alloantigen-specific control of transplant rejection. This approach based on fundamental knowledge of APC/T-cell interactions may complement conventional therapies in the near future to reinforce long-term allograft survival, and permit minimal immunosuppression. The focus of this review was primarily on two major co-inhibitory signaling pathways, namely PD-1/PD-L1/PD-L2 and BTLA/CD160/HVEM/LIGHT that have been thoroughly characterized in murine models of transplantation using genetically modified mice, specific monoclonal antibodies and fusion proteins. C1 [del Rio, Maria-Luisa; Rodriguez-Barbosa, Jose-Ignacio] Univ Leon, Immunobiol Lab, Sch Biotechnol, E-24071 Leon, Spain. [del Rio, Maria-Luisa; Rodriguez-Barbosa, Jose-Ignacio] Univ Leon, Inst Biomed, E-24071 Leon, Spain. [Buhler, Leo] Univ Hosp Geneva, Dept Surg, Surg Res Unit, Geneva, Switzerland. [Gibbons, Carrie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. [Tian, Jiong] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Kidney Dis Ctr, Hangzhou 310003, Zhejiang, Peoples R China. RP Rodriguez-Barbosa, JI (reprint author), Univ Leon, Immunobiol Lab, Sch Biotechnol, E-24071 Leon, Spain. EM ignacio.barbosa@unileon.es RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011; OI Rodriguez-Barbosa, Jose-Ignacio/0000-0001-7427-5654 FU Fondo de Investigaciones Sanitarias (Ministerio de Sanidad y Consumo, Spanish Government, Spain) [FIS 01-3026, FIS PI-050021] FX This work has been supported by grants FIS 01-3026 and FIS PI-050021 of Fondo de Investigaciones Sanitarias (Ministerio de Sanidad y Consumo, Spanish Government, Spain) to JIRB. NR 106 TC 27 Z9 30 U1 3 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD NOV PY 2008 VL 21 IS 11 BP 1015 EP 1028 DI 10.1111/j.1432-2277.2008.00726.x PG 14 WC Surgery; Transplantation SC Surgery; Transplantation GA 369WD UT WOS:000260723700001 PM 18662368 ER PT J AU Colli, JL Amling, CL AF Colli, Janet L. Amling, Christopher L. TI Exploring causes for declining prostate cancer mortality rates in the United States SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Ecology; Prostate cancer; Risk factors; United States; Epidemiology ID TRIAL; CELLS AB Objectives: Prostate cancer mortality rates in the U.S.A. increased in the late 1980s and declined from 1993 until 2003. The purpose of this study is to compare declining prostate cancer mortality rates among states with independent variables that may have an association to explore causes for the decline. Methods and materials: Annual rates of prostate cancer mortality for men over 50 were obtained from the National Vital Statistic System public use data file for states for individual years from 1993 to 2003. The annual rate of prostate cancer mortality decline for each state Was Calculated by the Joinpoint Regression Program (Statistical Research and Applications Branch of NCI). Annual rates of prostate cancer decline were cross-correlated to state levels of PSA screening, health insurance coverage, obesity, physical inactivity, diabetes, and high cholesterol for males front 45 to 64. Results: Declining prostate cancer mortality rates for white males correlated with high cholesterol levels (R = -0.42, P = 0.002) and PSA screening levels (R = -0.28. P = 0.05). Declining, prostate cancer mortality rates for black males correlated with health insurance coverage (R = -0.43. P = 0.03). Conclusions: Declining prostate cancer mortality rates are weakly associated with increased PSA screening for White Males but there was no association for black males, possibly because blacks have less access to medical care. The strong inverse correlation between declining prostate cancer mortality rates and levels of white males with high cholesterol levels was unexpected but may be associated with the widespread use of cholesterol reducing medications (statins), which are hypothesized to reduce prostate cancer risk. (c) 2008 Elsevier Inc. All rights reserved. C1 [Colli, Janet L.; Amling, Christopher L.] Univ Alabama, Dept Urol, Birmingham, AL 35294 USA. [Colli, Janet L.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Colli, JL (reprint author), Univ Alabama, Dept Urol, Birmingham, AL 35294 USA. EM jan.colli@ccc.uab.edu NR 9 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2008 VL 26 IS 6 BP 627 EP 633 DI 10.1016/j.urolonc.2007.05.016 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 377XH UT WOS:000261285100012 PM 18367111 ER PT J AU Zhang, LG Wang, CY Yang, R Shi, JD Fu, R Chen, LF Klocker, H Zhang, J AF Zhang, Liguo Wang, Chun-Yi Yang, Rui Shi, Jiandang Fu, Rong Chen, Linfeng Klocker, Helmut Zhang, Ju TI Real-time quantitative RT-PCR assay of prostate-specific antigen and prostate-specific membrane antigen in peripheral blood for detection of prostate cancer micrometastasis SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Real-time quantitative RT-PCR; Prostate-specific antigen (PSA); Prostate-specific membrane antigen (PSMA); Prostate cancer (PCa); Micrometastasis ID POLYMERASE-CHAIN-REACTION; MESSENGER-RNA; HEMATOGENOUS MICROMETASTASIS; PATHOLOGICAL STAGE; EXPRESSION; CELLS; PSA; ADENOCARCINOMA; HYBRIDIZATION; PROGRESSION AB Objective: Reverse transcription-polymerase chain reaction (RT-PCR) was, widely Used to detect disseminated tumor cells. However, high percentages of false-positive cases have been reported. Herein, we developed a method to detect prostate cancer (PCa) micrometastasis by real-time quantitative RT-PCR. Methods: Blood samples were obtained from 118 males, including, 13 healthy volunteers, 17 patients with metastatic PCa, 20 patients with localized PCa, and 68 patients with BPH. RNA was isolated from blood samples of different patients. Real-time RT-PCR was used to quantify file copy number of PSA and PSMA. The primers and probe of PSMA were designed to specifically discriminate between PSMA and PSM', an alternatively spliced variant. mRNA. Results: There was significant difference in the PSA and PSMA mRNA levels among BPH, locally confined PCa, and metastatic PCa blood specimens, The real-time quantitative RT-PCR is sensitive, accurate, and has a high reproducibility within a wide dynamic range (10(3)-10(8)), which permits simultaneous quantitative analysis of samples With varying input Concentrations. Conclusions: This method improves accuracy and liability of assessment of disseminated prostate cancer cells in peripheral blood and is promising for clinical diagnosis purpose. (c) 2008 Elsevier Inc. All rights reserved. C1 [Zhang, Liguo; Wang, Chun-Yi; Yang, Rui; Shi, Jiandang; Fu, Rong; Chen, Linfeng; Zhang, Ju] Nankai Univ, Inst Mol Biol, Minist Educ, Bioact Mat Key Lab, Tianjin 300071, Peoples R China. [Chen, Linfeng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Klocker, Helmut] Innsbruck Med Univ, Dept Urol, Innsbruck, Austria. RP Zhang, J (reprint author), Nankai Univ, Inst Mol Biol, Minist Educ, Bioact Mat Key Lab, Tianjin 300071, Peoples R China. EM zhangju@nankai.edu.cn RI Zhang, Liguo/E-2804-2014 NR 32 TC 19 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2008 VL 26 IS 6 BP 634 EP 640 DI 10.1016/j.urolonc.2007.07.016 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 377XH UT WOS:000261285100013 PM 18367130 ER PT J AU Gee, J Lee, IL Grossman, HB Sabichi, AL AF Gee, Jason Lee, I-Ling Grossman, H. Barton Sabichi, Anita L. TI Forced COX-2 expression induces PGE(2) and invasion in immortalized urothelial cells SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Transitional cell carcinoma; Cyclooxygenase-2; Prostaglandin E(2) ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; PROSTAGLANDIN E-2; BLADDER-CANCER; CYCLOOXYGENASE-2 INHIBITOR; COLORECTAL-CANCER; URINARY-BLADDER; APOPTOSIS; CELECOXIB; CARCINOMA AB Objectives: Cyclooxygenase 2 (COX-2) is aberrantly expressed in multiple tumor types including bladder cancer is associated with enhanced growth, resistance to apoptosis, invasion, and angiogenesis. To evaluate the mechanisms through which COX-2 expression alters normal urothelium, we transfected the SV-40 immortalized human urothelial cell line SV-HUC with COX-2. Methods: SV-HUC cells were stably transfected with a plasmid containing COX-2 Under a CMV promoter. Following isolation (of monoclonal transfectants, COX-2 expression was determined by Western and Northern analyses. Prostaglandin E(2) (PGE(2)) in the culture supernatant was measured by ELISA. Cell growth was measured by crystal violet assay. Cellular invasion through Matrigel and anchorage-independent growth in 0.4% agarose were assessed. Tumorigenicity was evaluated by subcutaneous injection of cells in nude mice with and without Matrigel. Results: Four of 12 clones stably overexpressing COX-2 at high levels relative to vector-transfected control cells were chosen for further study. Cell growth rates of these 4 clones were higher than vector control cells. PGE(2) production was elevated in 3 of these 4 clones, and PGE(2) levels correlated significantly with invasion through Matrigel. COX-2-transfected cells did not form colonies in soft agarose or tumors in nude mice. Conclusions: Forced COX-2 expression in SV-HUC immortalized urothelial cells contributes to increased PGE(2) production and increased invasion through Matrigel. However, it is insufficient to induce malignant transformation. (c) 2008 Elsevier Inc. All rights reserved. C1 [Gee, Jason] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. [Gee, Jason] Univ Wisconsin, Hosp & Clin, Div Urol, Madison, WI 53705 USA. [Lee, I-Ling; Grossman, H. Barton] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Sabichi, Anita L.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. RP Gee, J (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. EM gee@surgery.wisc.edu FU NCI NIH HHS [CA91846] NR 28 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2008 VL 26 IS 6 BP 641 EP 645 DI 10.1016/j.urolonc.2007.05.015 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 377XH UT WOS:000261285100014 PM 18367112 ER PT J AU Freedland, SJ Wen, J Wuerstle, M Shah, A Lai, D Moalej, B Atala, C Aronson, WJ AF Freedland, Stephen J. Wen, Joanne Wuerstle, Melanie Shah, Amy Lai, Dominic Moalej, Bita Atala, Christina Aronson, William J. TI Obesity Is a Significant Risk Factor for Prostate Cancer at the Time of Biopsy SO UROLOGY LA English DT Article ID BODY-MASS INDEX; RADICAL PROSTATECTOMY; WEIGHT CHANGE; SERUM-LEVELS; ANTIGEN; MEN; AGE; MORTALITY; PSA; HYPERPLASIA AB OBJECTIVES Studies suggest obesity is associated with decreased prostate cancer risk. We hypothesized obesity is biologically associated with increased risk, although this is obscured owing to hemodilution of prostate-specific antigen (PSA) and larger prostate size. METHODS We retrospectively studied 441 consecutive men undergoing prostate biopsy between 1999 and 2003 at two equal access centers within the Veterans Affairs Greater Los Angeles Healthcare System. We estimated the association between obesity (body mass index >= 30 kg/m(2)) and positive biopsy and Gleason >= 4+3 using logistic regression analysis adjusting for multiple clinical characteristics. RESULTS A total of 123 men (28%) were obese and 149 men (34%) had cancer. Median PSA and age were 5.7 ng/mL and 63.9 years, respectively. Obese men had significantly tower PSA concentrations (P = .02) and larger prostate volumes (P = .04). Obesity was not significantly related to age (P = .19) or race (P = .37). On univariate analysis, obesity was not associated with prostate cancer risk (odds ratio [OR] 1.13, 95% confidence interval [CI] 0.73-1.75, P = .58). However, after adjusting for multiple clinical characteristics, obesity was associated with significantly increased prostate cancer risk (OR 1.98, 95% Cl 1.17-3.32, P = .01). After multivariable adjustment, there was no significant association between obesity and high-grade disease (P = .18). CONCLUSIONS Without adjustment for clinical characteristics, obesity was not significantly associated with prostate cancer risk in this equal-access, clinic-based population. However, after adjusting for the lower PSA levels and the larger prostate size, obesity was associated with a 98% increased prostate cancer risk. These findings support the fact that current prostate cancer screening practices may be biased against obese men. UROLOGY 72: 1102-1105, 2008. (C) 2008 Elsevier Inc. C1 [Freedland, Stephen J.] Duke Univ, Sch Med, DUMC, Div Urol,Duke Prostate Ctr,Dept Surg, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Pathol, Duke Prostate Ctr, Durham, NC 27710 USA. Duke Univ, Vet Affairs Med Ctr, Urol Sect, Durham, NC 27710 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, DUMC, Div Urol,Duke Prostate Ctr,Dept Surg, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu FU Department of Defense; Department of Veterans Affairs, National Institute of Health [R01CA100938]; NIH Specialized Programs of Research Excellence [P50 CA92131-01AI]; American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF) FX Supported by the Department of Defense, Prostate Cancer Research Program (SJF); Department of Veterans Affairs, National Institute of Health Grant R01CA100938 (WJA), NIH Specialized Programs of Research Excellence Grant P50 CA92131-01AI (WJA), and the American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF). Views and opinions of, and endorsements by the authors do not reflect those of the US Army or the Department of Defense. NR 24 TC 40 Z9 42 U1 1 U2 4 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 NOV PY 2008 VL 72 IS 5 BP 1102 EP 1105 DI 10.1016/j.urology.2008.05.044 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 372OH UT WOS:000260910400043 PM 18722650 ER PT J AU Loeb, S Sutherland, DE D'Amico, AV Roehl, KA Catalona, WJ AF Loeb, Stacy Sutherland, Douglas E. D'Amico, Anthony V. Roehl, Kimberly A. Catalona, William J. TI PSA Velocity Is Associated With Gleason Score in Radical Prostatectomy Specimen: Marker for Prostate Cancer Aggressiveness SO UROLOGY LA English DT Article ID EXTERNAL-BEAM RADIATION; ANTIGEN; RISK; MEN; BRACHYTHERAPY; NOMOGRAM; THERAPY; RELAPSE; DEATH AB OBJECTIVES Conflicting evidence has been reported on the association of prostate-specific antigen velocity (PSAV) with Gleason score in prostate needle biopsy specimens. The Gleason score is an important prognostic indicator for men with prostate cancer, and, in modern practice, it frequently affects treatment decisions. To our knowledge, the relationship between preoperative PSAV and Gleason score in the radical prostatectomy specimen has not been formally demonstrated. METHODS A total of 1049 men treated with radical prostatectomy had data on PSAV and Gleason score. Statistical analysis was performed to examine the relationship between the preoperative PSAV and the prostatectomy Gleason score and other adverse tumor features. RESULTS The median preoperative PSAV was 0.84, 0.97, and 1.39 ng/mL/y in men with a Gleason score of 6, 7, and 8-10, respectively (P = .05). A PSAV greater than 2 ng/mL/y was significantly associated with a prostatectomy Gleason score of 7 or greater on univariate and multivariate analysis. In addition, the preoperative PSAV was significantly lower in men with organ-confined disease (0.82 vs 1.17 ng/mL/y, respectively, P = .002). CONCLUSIONS Our results have further validated PSAV as a marker for prostate cancer aggressiveness. The preoperative PSAV was a significant independent predictor of the Gleason score and non-organ-confined disease in the radical prostatectomy specimen. Thus, PSAV could be useful in treatment decision-making and in assessing the likelihood of long-term cancer control in men with prostate cancer. UROLOGY 72: 1116-1120, 2008. (C) 2008 Elsevier C1 [Catalona, William J.] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA. George Washington Univ, Sch Med, Dept Urol, Washington, DC USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Catalona, WJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 675 N St Clair St,Suite 20-150, Chicago, IL 60611 USA. EM wcatalona@nmff.org OI Loeb, Stacy/0000-0003-3933-9207 FU Urological Research Foundation; Beckman Coulter, Inc., Fullerton, CA FX This study was supported in part by the Urological Research Foundation and Beckman Coulter, Inc., Fullerton, CA. NR 17 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD NOV PY 2008 VL 72 IS 5 BP 1116 EP 1120 DI 10.1016/j.urology.2008.01.082 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 372OH UT WOS:000260910400046 PM 18571700 ER PT J AU Taussky, D Bae, K Bahary, JP Roach, M Lawton, CA Shipley, WU Sandler, HM AF Taussky, Daniel Bae, Kyounghwa Bahary, Jean-Paul Roach, Mack, III Lawton, Colleen A. Shipley, William U. Sandler, Howard M. TI Does Timing of Androgen Deprivation Influence Radiation-Induced Toxicity? A Secondary Analysis of Radiation Therapy Oncology Group Protocol 9413 SO UROLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol ID NEOADJUVANT HORMONAL-THERAPY; SERUM TESTOSTERONE LEVELS; PHASE-III TRIAL; PROSTATE-CANCER; CONFORMAL RADIOTHERAPY; SUPPRESSION; NORMALIZATION; MORBIDITY; CARCINOMA; ABLATION AB OBJECTIVES We conducted a secondary. analysis of the Radiation Therapy Oncology Group protocol 9413 to compare whether the timing of antiandrogen therapy (concomitant versus adjuvant) and testosterone levels influences the incidence of rectal and urinary toxicity in whole pelvic radiotherapy. METHODS We analyzed two of four study arms, in which all patients received radiotherapy to the whole pelvis followed by a boost to the prostate. The two arms differed solely in the timing of the total of 4 months of total androgen deprivation: arm 1 (320 patients, given concomitantly) and arm 111 (319 patients, given as adjuvant therapy). The influence of testosterone levels (measured at baseline and yearly thereafter) and its recovery on late rectal and urinary toxicity were modeled by multivariate logistic regression analysis and Fine and Gray's regression models. RESULTS The occurrence of late rectal toxicity (grade 0-1 versus 2-5, P = 0.16) and late urinary toxicity (grade 0-1 versus 2-5, P = 0.52) was not significantly different statistically between the two arms. The time to testosterone recovery was significantly lower in the adjuvant arm (mean difference of 3.2 months, P = 0.0103). Age and radiation field size are statistically significant risk factors for late urinary toxicity (P = 0.01 and P = 0.02). Baseline testosterone levels, before beginning total androgen deprivation, were a statistically significant predictive factor for late urinary toxicity (P = 0.03). CONCLUSIONS Older patients and patients with low testosterone levels at baseline are risk factors for late urinary and rectal toxicities, possibly through impaired tissue repair. UROLOGY 72: 1125-1129, 2008. (C) 2008 Elsevier Inc. C1 Univ Montreal, Dept Radiat Oncol, Montreal, PQ, Canada. Dept Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. Univ Calif San Francisco, Sch Med, Dept Radiat Oncol, San Francisco, CA 94143 USA. Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA. RP Taussky, D (reprint author), CHU Montreal, Hop Notre Dame, Dept Radiat Oncol, 1560 Sherbrooke St E, Montreal, PQ H2L 4M1, Canada. EM daniel.taussky.chum@ssss.gouv.qc.ca FU NCI NIH HHS [U10, CA21661, U10 CA37422, U10 CA32115] NR 21 TC 8 Z9 8 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 NOV PY 2008 VL 72 IS 5 BP 1125 EP 1129 DI 10.1016/j.urology.2007.11.067 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 372OH UT WOS:000260910400049 PM 18314175 ER PT J AU Buchanan, J Fleischmann, R Genovese, MC Kay, J Hsia, EC Doyle, MK Rahman, MU Han, C Parasuraman, S AF Buchanan, J. Fleischmann, R. Genovese, M. C. Kay, J. Hsia, E. C. Doyle, M. K. Rahman, M. U. Han, C. Parasuraman, S. TI GOLIMUMAB, A HUMAN ANTI-TNF-ALPHA MONOCLONAL ANTIBODY, SIGNIFICANTLY IMPROVES SELF-REPORTED PRODUCTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS FROM THREE PHASE 3 STUDIES SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Buchanan, J.; Han, C.; Parasuraman, S.] Johnson & Johnson Pharmaceut Serv LLC, Malvern, PA USA. [Fleischmann, R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genovese, M. C.] Stanford Univ, Palo Alto, CA 94304 USA. [Kay, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hsia, E. C.; Doyle, M. K.; Rahman, M. U.] Centocor Res & Dev Inc, U Penn Med Sch, Malvern, PA 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 NOV PY 2008 VL 11 IS 6 BP A557 EP A557 DI 10.1016/S1098-3015(10)66835-0 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 360JV UT WOS:000260054700671 ER PT J AU Romanus, D Oh, WK Cook, FE Weeks, JC AF Romanus, D. Oh, W. K. Cook, F. E. Weeks, J. C. TI SYMPTOM PREVALENCE IN HORMONE REFRACTORY PROSTATE CANCER (HRPC) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Romanus, D.; Oh, W. K.; Weeks, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cook, F. E.] Brigham & Womens Hosp, 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 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 NOV PY 2008 VL 11 IS 6 BP A487 EP A487 DI 10.1016/S1098-3015(10)66623-5 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 360JV UT WOS:000260054700459 ER PT J AU Romanus, D Neumann, PJ Earle, C Weinstein, MC Weeks, JC AF Romanus, D. Neumann, P. J. Earle, C. Weinstein, M. C. Weeks, J. C. TI THE IMPACT OF INITIAL TREATMENT CHOICE AND DISEASE PROGRESSION ON THE ECONOMIC BURDEN OF PATIENTS AND THEIR CAREGIVERS-A LONGITUDINAL STUDY OF STAGE IV NON-SMALL CELL LUNG CANCER (NSCLC) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Romanus, D.; Earle, C.; Weeks, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neumann, P. J.] Tufts Univ New England Med Ctr, Boston, MA USA. [Weinstein, M. C.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 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 NOV PY 2008 VL 11 IS 6 BP A482 EP A482 DI 10.1016/S1098-3015(10)66608-9 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 360JV UT WOS:000260054700444 ER PT J AU Weeks, JC Nelson, H Romanus, D Long, KH Sargent, D AF Weeks, J. C. Nelson, H. Romanus, D. Long, K. H. Sargent, D. TI ECONOMIC ANALYSIS OF THE CLINICAL OUTCOMES OF SURGICAL THERAPY (COST) TRIAL COMPARING LAPAROSCOPICALLY-ASSISTED COLECTOMY (LAC) WITH OPEN COLECTOMY (OC) FOR COLON CANCER SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Weeks, J. C.; Romanus, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nelson, H.; Long, K. H.; Sargent, D.] Mayo Clin, Rochester, MN 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 NOV PY 2008 VL 11 IS 6 BP A473 EP A474 DI 10.1016/S1098-3015(10)66581-3 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 360JV UT WOS:000260054700417 ER PT J AU Jaff, MR Goldmakher, GV Lev, MH Romero, JM AF Jaff, Michael R. Goldmakher, Gregory V. Lev, Michael H. Romero, Javier M. TI Imaging of the carotid arteries: the role of duplex ultrasonography, magnetic resonance arteriography, and computerized tomographic arteriography SO VASCULAR MEDICINE LA English DT Article DE carotid artery diseases; diagnostic; imaging ID ENHANCED MR-ANGIOGRAPHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; TRANSIENT ISCHEMIC ATTACK; ROW CT ANGIOGRAPHY; CONVENTIONAL ANGIOGRAPHY; ROTATIONAL ANGIOGRAPHY; SYMPTOMATIC PATIENTS; PSEUDO-OCCLUSION; HELICAL CT; STENOSIS AB Stenosis of the internal carotid artery represents a major cause of stroke, with atherosclerosis representing the major pathophysiology of this stenosis. It is estimated that over 700,000 Americans suffer a stroke annually. A prompt and accurate diagnosis of carotid artery disease is critical when planning a therapeutic strategy. Physical examination is inaccurate in determining the presence and severity of carotid artery disease. Therefore, reliable imaging tests which offer little risk to the patient are required. C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Div Cardiovasc Med, Sect Vasc Med, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Div Vasc Endovasc Surg, Boston, MA 02114 USA. [Goldmakher, Gregory V.; Lev, Michael H.; Romero, Javier M.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Vasc Ctr, Div Cardiovasc Med, Sect Vasc Med, 55 Fruit St,Gray Bigelow 832, Boston, MA 02114 USA. EM mjaff@partners.org NR 49 TC 35 Z9 37 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD NOV PY 2008 VL 13 IS 4 BP 281 EP 292 DI 10.1177/1358863X08091971 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 364MK UT WOS:000260339600007 PM 18940905 ER PT J AU Thomas, KA Joshi, M Wittenberg, E McCloskey, LA AF Thomas, Kristie A. Joshi, Manisha Wittenberg, Eve McCloskey, Laura A. TI Intersections of Harm and Health A Qualitative Study of Intimate Partner Violence in Women's Lives SO VIOLENCE AGAINST WOMEN LA English DT Article DE focus groups; intimate partner violence; women's health ID DOMESTIC VIOLENCE; PHYSICAL-DISABILITIES; CARE SETTINGS; ABUSED WOMEN; INJURIES; CONSEQUENCES; RISK AB Eight focus groups of women with recent exposure to intimate partner violence (IPV) were conducted to elicit women's descriptions of how IPV affects their health. Their shared narratives reveal a complex relationship with three main points of intersection between IPV and health: IPV leading to adverse health effects; IPV worsening already compromised health; and women's illness or disability increasing dependency on abusive partners, thereby lengthening the duration of IPV exposure. Women describe bidirectional and cyclical ways through which IPV and health intersect over time. Service providers, including physicians, need to better understand the myriad ways that abuse affects women's health. C1 [Thomas, Kristie A.; Joshi, Manisha] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Wittenberg, Eve] Brandeis Univ, Heller Sch Social Policy & Management, Schneider Inst Hlth Policy, Waltham, MA USA. [Wittenberg, Eve] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wittenberg, Eve] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Wittenberg, Eve] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCloskey, Laura A.] Merrill Palmer Skillman Inst, Detroit, MI USA. [McCloskey, Laura A.] Univ Arizona, Tucson, AZ 85721 USA. RP Thomas, KA (reprint author), Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. FU PHS HHS [200-2005-M-12079] NR 42 TC 17 Z9 17 U1 2 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD NOV PY 2008 VL 14 IS 11 BP 1252 EP 1273 DI 10.1177/1077801208324529 PG 22 WC Women's Studies SC Women's Studies GA 358TZ UT WOS:000259941700003 PM 18809846 ER PT J AU Grubaugh, AL Slagle, DM Long, M Frueh, BC Magruder, KM AF Grubaugh, Anouk L. Slagle, David M. Long, Mary Frueh, B. Christopher Magruder, Kathryn M. TI RACIAL DISPARITIES IN TRAUMA EXPOSURE, PSYCHIATRIC SYMPTOMS, AND SERVICE USE AMONG FEMALE PATIENTS IN VETERANS AFFAIRS PRIMARY CARE CLINICS SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH-SERVICES; VIETNAM VETERANS; NATIONAL SAMPLE; WOMEN VETERANS; SEXUAL ASSAULT; UNITED-STATES; GULF-WAR; PTSD; VA AB Objective. We sought to compare female African-American (n = 84) and Caucasian (n = 99) veterans from primary care clinics at 4 Veterans Affairs Medical Centers (VAMCs) on rates of trauma, posttraumatic stress disorder, other psychiatric diagnoses, functional status, and use of VA services and disability benefits. Methods. Analyses were based on a cross-sectional, epidemiologic design incorporating self-report measures, structured interviews, and chart reviews. Results. With the exception of higher rates of child sexual abuse among Caucasian women and higher rates of physical assault among African-American women, there were no other statistically significant racial differences across analyses. However, some clinically meaningful trends emerged, and the implications of these findings are discussed within the context of our other results. Conclusions. Among female veterans seen in VA primary care clinics, African-Americans and Caucasians do not differ dramatically with regard to the manifestation or severity of psychopathology, or in their use of relevant VA health care services and disability benefits. These data are important because women represent the fastest growing segment of the VA population after aging veterans. Further research is needed to replicate and extend these findings to ensure that female veterans' needs are adequately identified and met by VAMC providers. C1 [Grubaugh, Anouk L.] Med Univ S Carolina, Div Publ Psychiat, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Grubaugh, Anouk L.; Long, Mary; Magruder, Kathryn M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Slagle, David M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Frueh, B. Christopher] Baylor Coll Med, Menninger Clin, Houston, TX 77030 USA. [Frueh, B. Christopher] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Div Publ Psychiat, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. EM grubaugh@musc.edu NR 43 TC 13 Z9 13 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD NOV-DEC PY 2008 VL 18 IS 6 BP 433 EP 441 DI 10.1016/j.whi.2008.08.001 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 388BD UT WOS:000261994400002 PM 19041595 ER PT J AU Yu, J Zhu, H Ko, D Kindy, MS AF Yu, Jin Zhu, Hong Ko, Dorothy Kindy, Mark S. TI Motoneuronotrophic factor analog GM6 reduces infarct volume and behavioral deficits following transient ischemia in the mouse SO BRAIN RESEARCH LA English DT Article DE Stroke; Trophic factor; Middle cerebral artery occlusion; Mouse; Neuroprotection ID DEVELOPING NERVOUS-SYSTEM; FOCAL CEREBRAL-ISCHEMIA; SKELETAL-MUSCLE; BRAIN-INJURY; NEUROTROPHIC FACTORS; EXPERIMENTAL STROKE; GLOBAL-ISCHEMIA; CELL-DEATH; NEUROGENESIS; SURVIVAL AB Motoneuronotrophic factor (MNTF) is an endogenous neurotrophin that is highly specific for the human nervous system, and some of the observed effects of MNTF include motoneuron differentiation, maintenance, survival, and reinnervation of target muscles and organs. MNTF is a neuro-signaling molecule that binds to specific receptors. Using In Silico Analysis, one of the active sites of MNTF was identified as an analog of six amino acids (GM6). The effect of chemically synthesized GM6 on ischemic stroke was studied in the middle cerebral artery occlusion (MCAo) mouse model. Mice were subjected to 1 hur of ischemia followed by 24 h of reperfusion. Mice were injected intravenously with a bolus of GM6, at various doses (1 and S mg/kg) immediately after the start of reperfusion and examined for changes in physiological parameters, neurological deficits and infarct volume. GM6 was able to penetrate the blood brain barrier, and at both 1 and S mg/kg showed a significant protection from infarct damage, which translated to improvement of neurological deficits. Administration of GM6 demonstrated no changes in HR, BP, PO2, pCO(2), or pH. A significant increase over the control group in CBF after reperfusion was observed with GM6 administration, which helped to mitigate the ischemic effect caused by the blockage of blood flow. The time window of treatment was assessed at various times following cerebral ischemia with GM6 demonstrating a significant protective effect up to 6-12 h post ischemia. In addition, GM6 increased neurogenesis, and decreased apoptosis and inflammation in the mouse brain following cerebral ischemic injury. These data suggest that GM6 is neuroprotective to the brain following IV injection in the mouse model of MCAo. Published by Elsevier B.V. C1 [Yu, Jin; Zhu, Hong; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Ko, Dorothy] Genervon Biopharmaceut, Montebello, CA USA. [Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Kindy, Mark S.] Neurol Testing Serv Inc, Charleston, SC 29425 USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB 403, Charleston, SC 29425 USA. EM kindyms@musc.edu FU NIA NIH HHS [R01 AG019323-04, R01 AG019323] NR 60 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 31 PY 2008 VL 1238 BP 143 EP 153 DI 10.1016/j.brainres.2008.08.053 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 371UX UT WOS:000260858100015 PM 18789909 ER PT J AU Walsh, CA Morrow, EM Rubenstein, JLR AF Walsh, Christopher A. Morrow, Eric M. Rubenstein, John L. R. TI Autism and Brain Development SO CELL LA English DT Article ID FRAGILE-X-SYNDROME; SPECTRUM DISORDER; RETT-SYNDROME; NEURODEVELOPMENTAL DISORDERS; MENTAL-RETARDATION; CEREBRAL-CORTEX; MOUSE MODEL; MUTATIONS; GENES; MECP2 AB Genetic studies are refining our understanding of neurodevelopmental mechanisms in autism. Some autism-related mutations appear to disrupt genes regulated by neuronal activity, which are especially important in development of the postnatal nervous system. Gene replacement studies in mice indicate that the developmental window to ameliorate symptoms may be wider than previously anticipated. C1 [Walsh, Christopher A.; Morrow, Eric M.] Childrens Hosp, Dept Neurol, Div Genet, Boston, MA 02115 USA. [Walsh, Christopher A.; Morrow, Eric M.] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02115 USA. [Morrow, Eric M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94143 USA. RP Walsh, CA (reprint author), Childrens Hosp, Dept Neurol, Div Genet, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu RI Morrow, Eric/J-2767-2013 FU Howard Hughes Medical Institute; NIMH NIH HHS [K23 MH080954, K23 MH080954-05, R01 MH049428, R01 MH49428, 1K23MH080954, 1R01 MH083565, R01 MH083565-02, R01 MH083565]; NINDS NIH HHS [R01 NS034661, R01 NS035129, R01 NS34661] NR 42 TC 98 Z9 102 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 31 PY 2008 VL 135 IS 3 BP 396 EP 400 DI 10.1016/j.cell.2008.10.015 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 367EW UT WOS:000260536300007 PM 18984148 ER PT J AU Kelleher, RJ Bear, MF AF Kelleher, Raymond J., III Bear, Mark F. TI The Autistic Neuron: Troubled Translation? SO CELL LA English DT Article ID LONG-TERM DEPRESSION; FRAGILE-X-SYNDROME; OCULAR DOMINANCE PLASTICITY; DENDRITIC PROTEIN-SYNTHESIS; MAMMALIAN-CELL SIZE; SYNAPTIC PLASTICITY; MOUSE MODEL; TUBEROUS-SCLEROSIS; MENTAL-RETARDATION; SPECTRUM DISORDERS AB Autism is a complex genetic disorder, but single-gene disorders with a high prevalence of autism offer insight into its pathogenesis. Recent evidence suggests that some molecular defects in autism may interfere with the mechanisms of synaptic protein synthesis. We propose that aberrant synaptic protein synthesis may represent one possible pathway leading to autistic phenotypes, including cognitive impairment and savant abilities. C1 [Kelleher, Raymond J., III] Harvard Univ, Sch Med, Harvard Partners Ctr, Ctr Human Genet Res, Boston, MA 02115 USA. [Kelleher, Raymond J., III] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Neurosci,Autism Consortium, Boston, MA 02115 USA. [Kelleher, Raymond J., III] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Bear, Mark F.] Howard Hughes Med Inst, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Bear, Mark F.] MIT, Autism Consortium, Boston, MA 02115 USA. RP Kelleher, RJ (reprint author), Harvard Univ, Sch Med, Harvard Partners Ctr, Ctr Human Genet Res, Boston, MA 02115 USA. EM kelleher@helix.mgh.harvard.edu; mbear@mit.edu NR 60 TC 271 Z9 275 U1 1 U2 31 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 31 PY 2008 VL 135 IS 3 BP 401 EP 406 DI 10.1016/j.cell.2008.10.017 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 367EW UT WOS:000260536300008 PM 18984149 ER EF